Category: Medchem News

Inside the UW School of Pharmacy’s Mass Spectrometry Center

When Dale Whittington arrived at the University of Washington, he did not imagine that he would one day help shape one of the School of Pharmacy’s most consequential research facilities. Trained as a biologist, with a career path that briefly veered away from science altogether, Whittington eventually found his way back—drawn by the chance to work at the intersection of discovery, teaching, and problem-solving.

More than a decade later, as technical director and manager of the UW School of Pharmacy’s Mass Spectrometry Center, he oversees an operation that quietly underpins a wide range of scientific work. It is not a space defined by spectacle, but by precision: instruments that weigh molecules with extraordinary accuracy, revealing details that would otherwise remain invisible.

At its core, mass spectrometry rests on a deceptively simple principle. Molecules are given an electrical charge and guided through electromagnetic fields toward a detector. How they move—and how long they take to arrive—reveals their identity, structure, and abundance. From this information, researchers can determine molecular weights, concentrations, and subtle chemical differences that shape how drugs behave in the body.

From small molecules like amino acids to complex proteins and antibodies, mass spectrometry has become a foundational tool across chemistry, biology, and medicine. Its reach is broad, but its value lies in specificity.

From Molecules to Meaning

The real power of mass spectrometry emerges not from the instrument itself, but from the questions it allows scientists to ask. Researchers use it to track how medications are absorbed, distributed, and eliminated; to study how proteins change in disease; and to understand why a therapy may work well in one context but fail in another.

“This is the tool that lets us interrogate biological and chemical questions at a fundamental level,” Whittington says. “Whether you’re studying drug concentrations in tissue or changes in proteins during disease, mass spectrometry gives you a way to see what’s actually happening.”

For Mary Hebert, a professor of pharmacy and director of the UW’s Obstetric-Fetal Pharmacology Research Unit, the Center’s work is essential to understanding how medications behave during pregnancy and lactation—populations historically underrepresented in clinical research.

“The pharmacokinetics of most medications have not been studied in these populations,” she explains. “The Mass Spectrometry Center has made it possible to identify not only how drug handling changes during pregnancy, but also allows us to make informed predictions about other medications eliminated via similar pathways.”

Learning by Doing

What distinguishes the UW School of Pharmacy’s Mass Spectrometry Center is not only its technical capacity, but its approach to training. At many institutions, mass spectrometers are operated exclusively by specialists, with users receiving only processed data. At UW, students are encouraged to engage directly with the instruments themselves.

“Our goal is to train mass spectrometrists, not just data recipients,” Whittington says. “Students learn how to prepare samples, optimize methods, troubleshoot problems, and design experiments from start to finish.”

Graduate students progress quickly from observation to hands-on work. By their third session, many are expected to operate independently, with staff stepping in only when needed. The experience demystifies the technology—and builds confidence.

That experience carries weight beyond the university. Graduates trained at the Center enter industry and academic labs able to operate instruments, interpret results, and adapt methods with minimal supervision. Employers recognize the difference.

Medicinal Chemistry Affiliate Assistant Professor Kim Alonge, whose research focuses on the brain’s extracellular matrix, sees that impact firsthand in her trainees. “Direct access to mass spectrometry empowers them to generate and interpret complex datasets independently,” she says. “That accelerates their development as scientists and makes them more competitive for fellowships and careers.”

Expanding the Boundaries

While pharmaceutical research remains central to the Center’s mission, its applications extend far beyond drug development. Mass spectrometry has been used to analyze compounds in cannabis products, verify the composition of fish oil supplements, and even fingerprint wines to confirm their geographic origins.

One rapidly advancing area is MALDI imaging, a technique that allows researchers to map the spatial distribution of molecules within thin slices of tissue. The sample remains intact, preserving information about where compounds accumulate—or fail to reach.

This approach has reshaped understanding of HIV therapies by revealing uneven drug penetration in tissues, helping explain how viral reservoirs persist despite treatment. In neuroscience, it is opening new windows into the chemistry of the brain.

Using the Bruker timsTOF fleX platform, the only open access MALDI (matrix assisted laser desorption ionization) tissue imaging mass spectrometry in the northwest, UW students and researchers working with Alonge have mapped glycans in the hippocampus, uncovering spatial patterns linked to Alzheimer’s disease. “Without access to this facility—and this specific technology—those insights would not have been possible,” she says.

Looking ahead, Whittington sees artificial intelligence playing a growing role in managing the sheer volume of data mass spectrometry generates. “There’s more information than any one person can reasonably process,” he notes. “If we can apply AI in a careful, unbiased way, it may reveal patterns we’re not yet able to see.”

A Place to Grow

For Whittington, the appeal of the Center lies in its constant motion. Each project presents a new puzzle; each student brings a different way of thinking. The work resists routine.

“I feel fortunate to do something that’s always changing,” he says. “Between the teaching, the experiments, and the problem-solving, no two days are the same.”

For students and researchers alike, the Mass Spectrometry Center is more than a shared resource. It is a place where theory meets practice, where complex tools become accessible, and where careful measurement leads to clearer understanding.

As Hebert puts it, “There are critical questions—especially in pregnancy—that simply can’t be answered without highly sensitive, specific assays. Without this Center, we would not be able to quantify drug exposures that matter for both mother and child.”

In a field often defined by what cannot yet be seen, the Mass Spectrometry Center helps bring the invisible into focus—one molecule at a time.

Short Cut: What Does a Mass Spectrometer Do?

• A mass spectrometer is a scientific instrument that can be used to identify and measures molecules by their mass to charge ratio. It works by giving molecules an electrical charge and guiding them through electric or magnetic fields to elicit an electrical response on a detector. Because mass spectrometers can manipulate the transmission of molecules through electrical fields, the instrument can be used to determine what substances are present and ultimately help calculate much of each one there is. Scientists use mass spectrometers to study everything from how drugs move through the body, to how proteins change in disease, to where specific compounds are located within tissues. In short, mass spectrometry allows researchers to detect and measure chemicals with extraordinary specification and precision—often at levels far too small to see by any other method.

Resources:

• UW School of Pharmacy Mass Spectrometry Center
• Department of Medicinal Chemistry

The UWSoP Department of Medicinal Chemistry is proud to announce that PhD student Cristiana Meuret has been awarded the prestigious Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (F31)…

UW’s Board of Health Sciences Deans announced this week that fourth-year UWSOP Medicinal Chemistry student Alex Wiley has been named a 2023-2024 Magnuson Scholar. She is one of 7 awardees honored this year for both her academic performance and potential contributions to research in the health sciences.

Alex, a pre-doctoral candidate who works in Rheem Totah’s lab in the Department of Medicinal Chemistry, will receive $34,000 to support her education and research in the upcoming academic year.

Totah, a Medicinal Chemistry professor and associate chair, said Alex is a great role model and empowers others to become better scientists.

“Alex exemplifies the true nature of what it means to be a Magnuson Scholar,” she said. “She is an outstanding student in the lab, leading by example with an excellent work ethic and absolute grace under all the pressures of the past couple of years.”

Though she has had ample opportunities to explore many different research avenues and scientific disciplines, Alex says she found her home in pharmacy.

“My career path is more than a calling, it is a passion for learning, a desire to achieve,

and a drive for excellence,” she said, “but most importantly, it is a lifelong commitment. I am certain I have found ‘my reason’ through my circuitous undergraduate studies and here at UW.”

This prestigious scholarship is a tribute to Warren G. Magnuson, who represented Washington state in the U.S. Senate from 1944 to 1981, and in the U.S. House for the seven years preceding.

Led by Department of Medicinal Chemistry Assistant Professor Gaurav Bhardwaj, a team of researchers at the Institute for Protein Design, University of Washington have discovered how to create peptides that slip through membranes and enter cells. This #DrugDesign breakthrough may lead to new medications for a wide variety of health disorders, including cancer, infection, and inflammation.

Learn more about their work and the new #spinout that is licensing the platform and molecules described in the Cell Press paper:

Klarissa Jackson, ’13, has been awarded an ASPET 2022 Division for Translational and Clinical Pharmacology Early Career Award which recognizes excellence in translational and clinical pharmacology research developed by early-career scientists.

A 2013 UW School of Pharmacy postdoctoral fellow in the Department of Medicinal Chemistry, Dr. Jackson currently serves as assistant professor at UNC Eshelman School of Pharmacy in Pharmacotherapy and Experimental Therapeutics in Chapel Hill, NC.

Dr. Jackson received the award based on her translational research in drug metabolism/toxicology, focusing specifically on individual variations in cytochrome P450 enzymes. Her laboratory, supported by funding from the NIH National Cancer Institute Center to Reduce Cancer Health Disparities, the National Institute of General Medical Sciences, and the American Association of Colleges of Pharmacy, is focused on the roles of P450 and non-P450 enzymes in the metabolism and toxicity of small molecule drugs used in targeted cancer therapy.

Dr. Jackson is interested in understanding the impact of variability in drug metabolism and the disposition on individual risk for drug toxicity. Long-term, the goal of her research is to better predict and prevent adverse drug reactions and optimize drug therapy in diverse patient populations.

This award will be presented by the Division for Translational and Clinical Pharmacology at the ASPET annual meeting on April 4, 2022. There, Dr. Jackson will deliver a lecture on her research titled, Studies on the Role of Metabolic Activation in Tyrosine Kinase Inhibitor-Dependent Hepatotoxicity.

UWSOP would like to congratulate Amy Li, a 4th-year Medicinal Chemistry student in the UW XuLab, on being named a 2020-21 Magnuson Scholar! Amy studies the metabolism of cholesterol precursors, and how defects in that process relate to neurodevelopmental and metabolic diseases. She was selected on the basis of her excellent academic performance and outstanding potential for research in the health sciences.

Join us in welcoming Gaurav Bhardwaj, PhD, to the Faculty as Assistant Professor in the Department of Medicinal Chemistry. Gaurav earned his doctoral degree in Integrative Biosciences from the Pennsylvania State University. During his graduate work at Pennsylvania State University, he developed computational methods for studying evolution of highly divergent protein families.

From there, he undertook a post doctoral fellowship with Dr. Kit Lam at University of California, Davis, and then continued his post doc work at the Department of Biochemistry. He has been focused on the computational design of hyperstable constrained peptides and macrocycles with atomic-level accuracy, which opened avenues for custom design of peptide-based drugs that are cheaper, more effective and more stable than other alternatives.

“The UW Medicinal Chemistry department is very collaborative and features a broad diversity of expertise and resources, ranging from bioanalytical chemistry to drug metabolism,” said Gaurav. “Collaborations with other faculty members and students provide me a unique opportunity to accelerate the design and screening of new peptide-based therapeutics, as well as evaluate the pharmacokinetics and metabolism of these computationally-designed drug candidates.”

His lab is building a platform for the custom design of peptide-based therapeutics on computers. They are focusing on drug targets that are considered “undruggable” or ‘difficult-to-drug” using other therapeutic modalities—some of the most challenging problems in population health. His team is especially interested in designing novel antibiotics and non-opioid based solutions to treat chronic pain.

Gaurav’s work could lead to significant breakthroughs in the development of targeted peptide therapeutics—of interest to many pharmaceutical and biotech companies, including Genentech, which provided support for his research at the UW. In addition, the UW Institute of Protein Design (IPD)—an internationally renowned institute that aims to design and characterize proteins for a wide range of applications in medicine and material technologies—and the UW School of Pharmacy Dean contributed to the ‘start up’ funds to ensure Gaurav’s important and collaborative work would be based here at the UW.

Outside his lab work, Gaurav said he loves reading books and exploring all the state and national parks in the Pacific Northwest. He is currently reading 21 challenges for the 21st century by Yuval Noah Harari. A little known fun fact is that he was once an extra in a really bad zombie movie! But being a zombie in the lab is unlikely. When we asked the new Seattlite how he likes his coffee, he said, “I like a 16 oz Mocha, twice a day! In fact, the only piece of wall art in my new office says, “With enough coffee, anything is possible.”

Welcome to the UW School of Pharmacy, Gaurav!

The story of the Department of Medicinal Chemistry is of a multi-generational approach to solving big problems in population health.

“Our network of faculty, alumni, and students is working to solve problems that affect millions of people worldwide: dementia, HIV, influenza, and other therapeutic areas. We train people to work at the molecular level to find better therapies and increased insight into these conditions.”—Bill Atkins, Sid and Joan Nelson Endowed Professor and Chair, UW Department of Medicinal Chemistry

Understanding and breaking down the mysteries embedded in small molecules and their mechanics is an effort that takes generations, not years, and one that accelerates as technology improves. No better place can that acceleration be seen than in the UW Department of Medicinal Chemistry.

Originally one department of pharmaceutical sciences, Dean Milo Gibaldi split it into pharmaceutics and medicinal chemistry to distinguish the disciplines. Looking back over the decades, we can see the Med Chem community like a family tree.

Faculty member Alain (Al) Huitric was a pioneer in applications of proton nuclear magnetic resonance (NMR) , recognizing its use for solving problems
of structural organic chemistry, and was a mentor to many. Dean Emeritus Sid Nelson said Al inspired him to pursue teaching and research. Bill Trager received his PhD in Med Chem under Al’s direction and Bill, Sid, and Allan Rettie all worked in his lab.

Forty years ago, Al secured funding for an NIH National Institute of General Medical Sciences (NIGMS) pharmacological sciences predoctoral training grant, which has been a significant source of support
for our graduate students. It is the longest continually running grant in UWSOP history. Training grants like this, research grants, and private support are critical with the waning of state support for research training. The UWSOP Corporate Advisory Board, one of the first corporate boards at the UW and vital partnership, was founded just over twenty years ago and brings our faculty and students together with leaders in the pharmaceutical industry, to enhance collaboration, training, networking, and research opportunities.

With its roots in the leadership of the Med Chem chairs 
Bill, Wendel Nelson, Allan, Kent Kunze, and Bill Atkins, Med Chem has trained graduate students and post docs who are now leaders in industry and academia, including: Larry Wienkers,’93, who went to Amgen and is a global leaderin P450-related drug metabolism research; Cyrus Khojasteh, ’98, an internationally recognized expert in drug metabolism and pharmacokinetics and the first drug metabolism expert at Genentech; Pharmacy assistant professor Cathy Yeung, ‘05, part of the Kidney on a Chip team; and Klarissa Jackson, who trained with Sid Nelson and Allan Rettie and went on to earn the first NIH grant in the history of Lipscomb University and is now at University of North Carolina College of Pharmacy. Med Chem continues to grow and thrive with innovative researchers like Rheem Totah, Abhi Nath, ’08, Libin Xu, Kelly Lee, and Mike Guttman, who was a post doc in the Lee Lab.

Mass Spectrometry

In the late 1970s, applications of mass spec technology to drug metabolism and pharmacokinetics became more prevalent, leading Bill Trager and Bill Howald to establish the UW Mass Spec Lab. When Tom Baillie joined Med Chem, he and Bill Howald acquired the latest equipment to support research across both departments, developing the interdisciplinary UW Mass Spectrometry Center.

To study with UWSOP’s top faculty in health economics and outcomes, medicinal chemistry, and pharmaceutics, click here for more information about our Graduate Programs in Medicinal Chemistry, Pharmaceutics, Pharmaceutical Outcomes Research and Policy, and Biomedical Regulatory Affairs.

In 2018, Abhi Nath, ’08, was named recipient one of that year’s UWSOP Faculty Innovation Awards. The awards provide financial support of up to $20,000 each for high-risk, innovative research projects.

Abhi proposed to look at new ways to predict how the body metabolizes biologics, also known as “large-molecule” drugs or protein-based therapeutics. These drugs display immense potential in the treatment of many challenging forms of cancer, autoimmune disorders, and infectious and degenerative diseases. However, a major hurdle to their development is a lack of understanding of the factors that govern their pharmacokinetics and disposition.

“We don’t yet recognize the ‘flags’ that indicate that a given large molecule may behave problematically or unpredictably, as we do for conventional small molecule drugs.” —Abhi Nath, Assistant Professor of Medicinal Chemistry

This knowledge gap makes the development of biologics challenging, increasing the time and costs to bring these promising medications to market. By using a combination of biophysical measurements and machine learning analyses, the team anticipated they would shed new light on the disposition of protein-based therapeutics, and give trainees hands-on experience in modern data science techniques.

Thus far, the UWSOP Faculty Innovation Award has led to one publication by Medicinal Chemistry PhD graduate student Dennis Goulet, former Magnuson Scholar and first recipient of the Scott Grimm Fellowship. Dennis is first author on, “Toward a Combinatorial Approach for the Prediction of IgG Half-Life and Clearance” in ASPET’s Drug Metabolism and Disposition. The paper’s co-authors include Michael J. Watson, William M. Atkins, and Abhinav Nath, all from the UWSOP Department of Medicinal Chemistry, as well as colleagues from Janssen Research & Development.

In addition, Medicinal Chemistry PhD graduate student Hayli Larsen will present work enabled by the award at the Protein Society Annual Meeting in Seattle this summer.

Past recipients of the Faculty Innovation Award include:

• Pharmacy’s Brian Werth and grant coinvestigator UWSOP Medicinal Chemistry’s Libin Xu who continue their novel research into antibiotic resistance mechanisms in the superbug, methicillin-resistant Staphylococcus aureus (MRSA) with the support of a recent 4-year, $1.86 million NIH R01 grant.

• An interdisciplinary team led by CHOICE Associate Professor Beth Devine, with Pharmaceutics’ Isabelle Ragueneau-Majlessi, ’10, and Pharmacy’s Jennifer Wilson-Norton, ’93, earned the award for their proposal, “Evaluating the Impact of Pharmacogenetic Testing on Clinical Outcomes in Retirement Communities: A Proof-of-Concept Feasibility Study.” UWSOP’s Jennifer Bacci, and Basia Belza, from the UW School of Nursing, will serve as advisors.

• Professor Allan Rettie is leading a team that includes Co-Investigators Pharmaceutics Assistant Professor Bhagwat Prasad and Shreeram Akilesh of Pathology to find new personalized ways to slow the progression of the development of breast cancer by focusing in on an enzyme that can go rogue. The team hopes to identify inhibitors of a gene, CYP4Z1, which codes for a cytochrome P450 enzyme that is strongly associated with progression of the disease, a breakthrough that could lead to improved therapies that are personalized for a patient’s particular type of breast cancer.

To study with researchers like Dr. Nath and peers like Dennis Goulet and Hayli Larsen, click for more information about our Graduate Programs in Medicinal Chemistry.

Link to Medicinal Chemistry archived news

Congratulations to UWSOP Outstanding Dissertation Award winner Dennis Goulet, Medicinal Chemistry, and Graduate Student Leadership Award for Medicinal Chemistry, Benjamin Maldonato.

The UW School of Pharmacy Graduate Program Awards offer special recognition of our preeminent graduate students and faculty.

Outstanding Dissertation Award:  Dennis Goulet, Medicinal Chemistry

The UWSOP Outstanding Dissertation Award celebrates a graduate student who has conducted outstanding research at the doctoral (PhD) level. This year we celebrate Dennis Goulet, whose dissertation, “Biophysical Approaches for the Development of Stable, Long-Lived, Multi-Functional, and Potent Antibody Therapeutics,” was selected for UWSOP’s Outstanding Dissertation Award.

Dennis’ thesis work was highly impactful in several ways. His thesis concerned several aspects of therapeutic antibodies including the design of some novel constructs with potential new properties. His work also had a significant impact in the field of antibody design and characterization, resulting in five manuscripts published in excellent journals and he is first author on four of them, among other pending articles. Dennis developed a novel method with fluorescence correlation spectroscopy, to monitor antibody behavior in serum that sheds new light on how antibodies behave.

Dennis has demonstrated excellence throughout his graduate work here at UWSOP. In 2017, he was awarded the first Scott Grimm Memorial Scholarship and the prestigious UWSOP Magnuson Scholarship. From 2014-2016, he had a Pharmacological Sciences Training Grant, National Institutes of Health and from 2013-2016, he had an ARCS Fellowship.

Congratulations Dennis!

Graduate Student Leadership Award: Benjamin Maldonato, Medicinal Chemistry

The UWSOP Graduate Student Leadership Awards honors one graduate student in each of our three departments who has demonstrated outstanding leadership and service that has had a positive impact on the School of Pharmacy, UW, the Northwest community, scientific and/or professional community. Benjamin Maldonato received this year’s UWSOP Medicinal Chemistry Student Leadership Award. Ben is a senior graduate student in the Med Chem department, conducting his thesis research in Dr. Rheem Totah’s lab. He is well-regarded for his understanding the value of community and how to contribute to its strength, often leading or organizing events that benefit both Medicinal Chemistry and Pharmaceutics.

Ben has been very active in supporting the annual UW student chapter of the American Association of Pharmaceutical Scientists (AAPS)serving as Secretary, as well as NIH Predoctoral Training Grant events. In addition, he has been actively involved in student recruitment over the last several years, showing initiative in volunteering to support these important events. He has served as a judge for the Central Sound Science Fair (CSSF) which brings high school students from King and Snohomish counties together to present their science projects. In that role, he talks with students about their projects and ensures they have included proper controls, considered alternative strategies, undergone optimization, and utilized rigorous statistics.

Ben has been a trainee on both the UW ITHS TL1 Multidisciplinary Predoctoral Clinical Research Training Program and the UW Pharmacological Sciences Training Program. In 2017, he presented at the Gordon Research Conference on Drug Metabolism and will intern in the highly-competitive Drug Metabolism Pharmacokinetics (DMPK) department of Boehringer Ingelheim this summer.

Congratulations Ben and thank you for your leadership and mentoring!

To study with peers like Dennis and Benjamin, click for more information about our Graduate Programs in Medicinal Chemistry.

Link to Medicinal Chemistry archived news

Professor Allan Rettie, Medicinal Chemistry, was nominated for and selected at the 2019 Outstanding Graduate Student Mentor by colleagues and current and former students.

“Allan encouraged his students to critically analyze internally and externally generated data,” said one former graduate student. “When students started to ask interesting questions, we were encouraged to develop strategies and methods to find the answers. He provided us with the guidance, the time, and resources to conduct the necessary studies.”

Known for his high level of support for his students, as well as his own research excellence, Allan earned this year’s mentorship award. For 11 years, Allan served as the Director of the NIH T32 Predoctoral Training Program in Pharmacological Sciences. This interdepartmental training grant supports students from the Departments of Medicinal Chemistry, Pharmaceutics, and Pharmacology, and has been continuously funded for 40 years. In addition, he has served as the Graduate Program Coordinator for the Department, responsible for student recruitment and advising.

“Allan has truly been a major contributor to the education of the current cohort of drug metabolism scientists that are scattered throughout the pharmaceutical industry and academia,” wrote one colleague.

Congratulations to Professor Allan Rettie for your recognition as Outstanding Graduate Student Mentor!

To study with peers like faculty like Allan Rettie, click for more information about our Graduate Programs in Medicinal Chemistry.

Link to Medicinal Chemistry archived news

The UW Medicinal Chemist studied neural chemistry and biology to understand the underlying mechanism that cause birth defects, behavioral problems, and autism

You probably know about good and bad cholesterol as it relates to your heart—but did you know that your brain needs cholesterol too? The brain’s cholesterol is essential to fetal development—a lack of which can lead to birth defects and conditions like Smith-Lemli-Opitz syndrome (SLOS), a disorder caused by mutations in the last step of cholesterol biosynthesis, DHCR7.

SLOS has a high correlation with autism: over 70% of children diagnosed with SLOS also display an autism spectrum disorder. It also tends to be underdiagnosed due to fetal lethality or takes years to be diagnosed as some mild cases show up as behavioral problems, not physical defects.

But getting more cholesterol to the brain isn’t as simple as taking a supplement. The brain makes its own cholesterol and cholesterol in the peripheral tissues or blood does not cross the blood-brain barrier. Any therapies for SLOS must be able to pass through the blood-brain barrier to be effective.

Assistant Professor Libin Xu and his team want to understand the molecular mechanisms underlying SLOS so they can test treatments that can get to the brain. Understanding the mechanisms behind SLOS could also lead to treatments for autism due to the strong correlation between SLOS and autism.

“The marriage of chemistry and biology gives me a unique way to look at molecules and the impact small molecules have in disease pathology.”—Libin Xu, Assistant Professor of Medicinal Chemistry

There are two causes the team are looking at: genetic mutations in DHCR7 that result in a build up of a reactive cholesterol precursor, 7DHC, that negatively affects brain development, as well as inhibition of the same enzyme by environmental molecules or drugs, such as benzalkonium chloride, a common ingredient in hand wipes and disinfectants like Clorox and Lysol, and some antipsychotic and antidepressant drugs—such as Abilify and Haldol. 

Simply put, the team is exploring how these common environmental compounds and prescription medications cause the same biochemical  defects observed in SLOS, aiming to minimize damages of such exposure on embryonic and brain development and develop treatments.

The team is using a combination of mass spectrometry and mouse models to study the disease and what happens when the reactive cholesterol precursor, 7DHC, builds up. They want to find a way to inhibit the formation of toxic metabolites of 7DHC or inhibit their downstream detrimental effects using small molecules. Libin sees some promise in identifying combination therapies that mitigate the risk of SLOS-like symptoms in the case of mothers taking antidepressants or antipsychotics.

Women who are expecting may want to speak with their doctor if they are taking such drugs or using products containing benzalkonium chloride during pregnancy and lactation. However, there are adverse side effects of untreated depression, including low birthweight and preterm labor, which may outweigh the risk to the fetus’ development, so stopping medication without a provider’s guidance is not recommended.

This five-year National Institutes of Health R01 grant (R01HD092659) was funded in 2017 for $1.3M.

To study with researchers like Dr. Xu, click for more information about our Graduate Programs in Medicinal Chemistry.

Link to Medicinal Chemistry archived news

We revisited Abhi Nath and his lab team to see how their work to improve the diagnosis and treatments of neurodegenerative conditions, including Alzheimer’s, Parkinson’s, and Chronic Traumatic Encephalopathy (CTE) was progressing.

The team hopes to discover improved diagnostic tools and therapies by learning how brain proteins such as Tau, β-Amyloid and α-Synuclein start misbehaving in these diseases.

The challenge is that proteins like Tau are very flexible moving targets, almost like Jell-O™, making it hard to use traditional tools of structural biology. One of their long-term goals is to develop new small molecules that can either slow down protein aggregation, or bind to particular types of aggregates to act as a tracer.

Such tracers or tags can currently be used to detect protein aggregates in brain scans, but struggle to distinguish which particular proteins are involved, or whether aggregates are harmful or benign.

“Newer, more specific tracers could enable earlier, more accurate diagnosis of conditions like Alzheimer’s and Parkinson’s and ultimately improve outcomes for patients and their families.”–Abhi Nath

Graduate student David Baggett’s computer models can screen millions of compounds to identify molecules capable of binding proteins like Tau, and either detecting or stopping the aggregation process. As they learn more about how these compounds recognize Tau, they can perhaps engineer more effective, safer variants that could serve as the basis for new treatment and diagnosis strategies.

A new industry partnership with Takeda Pharmaceutical Co. will accelerate their research. “The Takeda award provides us with support and resources to work on designing, synthesizing, and testing new molecules— derivatives of ones that David found,” shared Abhi. “We will also use his methods to identify other novel molecules with similar activity.”

Hope Barnes Fellow and graduate student Hannah Baughman continues to discover more about molecular chaperones, which are natural defenders against protein aggregation. The NIH recently elected to support this work under a special program for Alzheimer’s disease and related dementias.

“If we can turn up the right sort of activity for the right type of chaperone, that may advance our ability to treat Alzheimer’s, Parkinson’s, and CTE,” said Abhi. “My vision is to use the advances that have been made in protein biophysics over the past 10–15 years to find new ways to diagnose these conditions early and improve treatments and outcomes for patients. Given how much we have learned about Tau and similar proteins, and our partnerships in academia and industry, I am very excited about our prospects.”

To study with researchers like Dr. Nath with peers like Hannah Baughman, click for more information about our Graduate Programs in Medicinal Chemistry.

Visit the Nath Lab website

Link to Medicinal Chemistry archived news

It’s bittersweet to announce that our long-time colleague, Dr. Kent Kunze, has stepped down as Departmental Chair and retired from the faculty.  Kent has been a valued member of the faculty since 1990, and for the past 4 years he has served as ‘the Chair.’  During his time on the faculty, Kent played a critical role in the research activities that further strengthened our ‘brand’ in drug interactions and mechanistic drug metabolism.

Kent has continued to be a resource for all seeking expertise in Cytochrome P450 enzymology and inhibition.  Most recently, Kent provided leadership and vision that helped to launch new research initiatives of our younger faculty.  Kent says that the near future includes some golf, sailing, and hiking. We wish him a happy retirement and say a heartfelt ‘thanks’ for being an important part of our village.

Lipid peroxidation is the process in which a reactive atom or group of atoms (free radicals) capture electrons from the lipids in cell membranes, resulting in cell damage. This process plays an important role in the pathophysiology of many human conditions – aging, atherosclerosis, cancer, and neurodegenerative diseases – so it is critically important to understand the mechanisms by which these molecules are oxidized.

The Libin Xu lab in Medicinal Chemistry has been awarded a three-year grant from the National Science Foundation in the amount of $405,000, which the lab will use to research the fundamental chemistry of free radical oxidation of organic molecules, including biologically important lipids and vitamins.

“The goal of this grant is to develop a chemical method, called ‘peroxyl radical clock,’ to measure the rate-determining steps of lipid peroxidation,” said Dr. Xu. “We want to understand the reaction mechanisms of biologically important lipids, including the biosynthetic precursors of cholesterol, arachidonic acid (in collaboration with my colleague Dr. Rheem Totah), and fat-soluble vitamins A, D, and K.”

This project could have broad benefits to human health: understanding the reactivity of these lipids would allow the team to assess the susceptibility of human tissues to oxidative stress, particularly when the levels of oxidizable lipids are elevated. The oxidation products can also be biomarkers of human disease. Many of these products have some detrimental effect on physiological processes, and being able to measure and assess them would give health scientists more information on which to base effective therapies.

“Most of the preliminary data for this project was generated by outstanding undergraduate researchers in my lab,” said Dr. Xu. “Andrew Dinh, David Lee, and David Kennedy have all moved on to the next chapter of their careers, but they made a strong impact on our research. I was very fortunate to work with them during the startup years of my lab.” He added, “This is a good example of how undergraduate researchers can truly contribute to basic science.”

To study with researchers like Dr. Xu, click for more information about our Graduate Programs in Medicinal Chemistry.

Link to Medicinal Chemistry archived news

Theresa Aliwarga, a Medicinal Chemistry graduate student and researcher in Rheem Totah’s lab, was invited to give a podium presentation of her research on CYP2J2-mediated epoxyeicosatrienoic acids (EETs) as potential markers for cardiovascular disease at this summer’s Gordon Research Conference in Drug Metabolism.

“I was able to show that a higher level of EETs is associated with lower risk of sudden cardiac arrest,” she said. “Cardiovascular disease remains the leading cause of mortality globally,” she stated. “If monitoring EET levels could be used to detect anomalies in the heart, it could prevent a lot of damage associated with cardiovascular disease.“

To study with faculty like Rheem Totah and peers like Theresa Aliwarga, click for more information about our Graduate Programs in Medicinal Chemistry.

Link to Medicinal Chemistry archived news

William “Bill” Howald passed away August 14, 2017 in Salem, Oregon at the age of 76 after a brief illness. After retirement, Bill and his wife Carole moved to Oregon to be closer to family.

Bill joined the School of Pharmacy, Department of Medicinal Chemistry as a Research Technologist working in the Mass Spectrometry Facility. He became the Manager of the Facility and Lecturer in Medicinal Chemistry in 1983 and retired in 2008 after building a world class center.

During his tenure the Mass Spectrometry Center provided cutting edge mass spectrometers and other tools to support the diverse and evolving research programs in proteomics, drug metabolism and biochemical toxicology in the School of Pharmacy as well as the in the larger UW research community. He played an essential role in the research productivity of the school working closely with Bill Trager, Tom Baillie, Sid Nelson, Allan Rettie, Rene Levy, Ken Thummel and countless others.

Perhaps equally significant to the mountains of his research accomplishments was the extensive hands-on training that Bill provided to the many generations of graduate students and post-doctoral fellows that have moved through our training programs. These scientists, now spread through the world, provide a long and lasting testimony to Bill’s legacy.

Mass spectrometers are expensive, powerful, and unfortunately highly temperamental instruments. Medicinal Chemistry department chair Kent Kunze said, “Training new students required the endless patience and a good sense of humor for which Bill was famous. Bill was a consummate scientist and wonderful colleague and friend to all.”

The family has asked that gifts in remembrance of Bill’s life and work be made to the William Howald Mass Spectrometry Support Fund at the UW School of Pharmacy at http://bit.ly/BHowald. 

Link to Medicinal Chemistry archived news

The Royalty Research fund (RRF) is sponsored by UW’s Office of Research to help faculty establish new research programs.  The program is funded from royalty and licensing fee income generated by the UW Technology transfer program.  These one-year awards have been offered semi-annually since 1992.

Med Chem Assistant Professor Mike Guttman was recently chosen to receive an RRF award of $36,665 for his project, “Gas Phase Hydrogen/Deuterium Exchange to Distinguish Isomeric Carbohydrates.”  Dr. Guttman’s aim is to develop new mass spectrometry techniques for analyzing various sugar structures.

A variety of complex sugar structures cover most of the extra-cellular environment of higher-level organisms.  Many of the sugars regulate host-pathogen interactions and modulate the immune system.  “We want to understand the detailed structures of the sugars associated with disease onset,” said Guttman, “to find new ways of preventing pathogens from infecting cells in the first place, or detecting and targeting cancer cells.”

The current techniques for doing this are somewhat limited, so Dr. Guttman wants to create a novel analytical tool using recent developments in gas-phase structural analysis in combination with existing glycobiology platforms.  “This kind of rapid technology will enable large-scale studies to better understand how various sugar structures regulate the immune response and modulate tumor progression,” said Guttman.  “It will also provide a new way to characterize the next generation of biotherapeutics.”  He added, “I’m grateful to receive the RRF award that will help us move forward on this project.”

To study with researchers like Dr. Guttman, click on the links for more information about our Graduate Programs in Medicinal Chemistry, Pharmaceutics, Pharmaceutical Outcomes Research and Policy, and Biomedical Regulatory Affairs.

Scott Grimm Scholar and Medicinal Chemistry graduate student Dennis Goulet (Bill Atkins lab) has been awarded the prestigious Magnuson Scholarship for 2017-2018, receiving the $30,000 award on the basis of his outstanding academic performance and potential contributions to research in the health sciences. The scholarship is funded from a $2 million endowment from the Warren G. Magnuson Institute for Biomedical Research and Health Professions Training. The University names six Magnuson Scholars annually, one from each of the health sciences schools. Awardees are selected based on their academic performance and potential contributions to health sciences research.

Dennis joined the Atkins lab in 2014 and was selected as a trainee on the NIH-sponsored Pharmacological Sciences Training Grant. Dr. Atkins noted, “Dennis is certainly deserving of this recognition, and I’m lucky to work with him.” As a Magnuson Scholar, Dennis will focus on how fundamental biophysical properties of proteins are related to their safety and efficacy as therapeutics. “As one example,” said Dennis, “we are trying to understand how binding of antibodies to certain receptors affects their stability in the serum.” Such research could be used to moderate the biological half-life of antibody-based therapeutics, allowing patients to receive IV drugs less frequently, while maintaining an efficacious dose.

“It is such an honor to be selected for this prestigious award,” said Dennis. “I am humbled to be representing Medicinal Chemistry and the School of Pharmacy among such a talented group of scholars.”

Congratulations to Dennis on this awesome award!

To study with peer researchers like Dennis Goulet, click on the links for more information about our Graduate Programs in Medicinal Chemistry, Pharmaceutics, Pharmaceutical Outcomes Research and Policy, and Biomedical Regulatory Affairs.

Scott W. Grimm was a long-time friend of Medicinal Chemistry and the School of Pharmacy.  A Corporate Advisory Board member who enthusiastically supported our students and programs, he was also a leader in drug discovery and development via his 27-year career with AstraZeneca.  When Scott died in 2014, his family and colleagues established a permanent endowed fund in his name to support a high-achieving graduate student in Medicinal Chemistry, whose research supports the fight against brain cancer.

The Scott Grimm Memorial Scholarship is being awarded for the first time in 2017, to Med Chem graduate student Dennis Goulet, whose work in therapeutic antibodies supports cancer research.  Dennis will receive $1,000 towards expenses, such as travel and lab supplies, that are related to his research.

“I am very grateful to the family of Scott Grimm for their generous sponsorship of pharmaceutical research at UW,” said Dennis.  “This award will support my studies on the biophysical properties of antibodies and their relation to the safety and efficacy of antibody therapeutics.”

Congratulations to Dennis on this award!

Link to Medicinal Chemistry archived news

Congratulations to Medicinal Chemistry graduate student, Amy Li, who was recently awarded an ARCS Fellowship.

The Seattle Chapter of ARCS Foundation contributes to the advancement of science and technology by funding PhD fellowships for academically outstanding scholars in the fields of science, technology, engineering, and math at the University of Washington and Washington State University.

Congratulations, Amy!

The American Foundation for Pharmaceutical Education’s Pre-Doctoral Award in Pharmaceutical Science has been awarded again to Med Chem graduate student Robert Pelletier (Kent Kunze lab). Pelletier has received a renewal of this Fellowship through August 2017, with another stipend of $10,000, to support his thesis project, “Mechanism of CYP2E1 Inhibition by Chlormethiazole.” He will continue to explore the potential of chlormethiazole to inhibit CYP2E1’s ability to cause toxic reactions in substances such as the over-the-counter drug acetaminophen. See the original article for more details, at https://sop.washington.edu/pelletier-wins-afpe-award/.  Congratulations, Robert!

Link to Medicinal Chemistry archived news

Dr. Thomas Baillie, Professor of Medicinal Chemistry and Dean Emeritus for the UW School of Pharmacy, has announced that he will be officially retiring from the University of Washington in March of 2016. Tom has had an enormous positive impact on the School of Pharmacy. He has been a tireless and highly effective advocate for our research, teaching and training missions within the School, UW, and across industry. Over the years, he has been a strong mentor and keen supporter of our faculty, students, trainees and alumni. Tom’s leadership and organizational skills were crucial to the continued success of our school during the financial austerity imposed by the recession of 2008. He led us through a difficult curricular revision process triggered by major changes in accreditation standards that ultimately led to full accreditation for the school.

Tom Baillie joined the faculty of the Department of Medicinal Chemistry in 1981. He conducted a vigorous NIH funded research program in mass spectrometry, biochemical reaction mechanisms and toxicity. In 1994, Tom accepted an opportunity to join Merck & Co. as the Executive Director of Preclinical Drug Metabolism in West Point. He rose through the ranks at Merck where he was awarded the position of Vice President and Global Head of Drug Metabolism and Pharmacokinetics. A key member of Merck leadership team, he was also responsible for a group of 350 scientists and staff spread over multiple locations worldwide. While at Merck, Tom maintained strong ties to the school and faculty and fostered close relations between the two institutions. In 2008, he and his wife Kathleen returned to Seattle when he was appointed Dean of the School of Pharmacy and Professor of Medicinal Chemistry. During his tenure as Dean, Tom served as Chair of the Board of Health Sciences Deans and Vice Provost for Strategic Initiatives at the University of Washington. Having seen the School through the economic crisis and our successful reaccreditation, he stepped down as Dean at the end of his term in 2014 and returned to a full time appointment in the Department of Medicinal Chemistry.

During his long career as a scientist, Tom has made many high profile contributions in the areas of drug metabolism, drug toxicity and drug safety particularly as they relate to the drug discovery process. He is an author on over 250 publications and was recognized as one of the topmost cited (top 1%) researchers in the area of Pharmacology & Toxicology by Thompson Reuters for work begun here at UW in collaboration with our late Dean Emeritus Sid Nelson. He has received numerous honors and awards including a Fogarty Senior International Fellowship from the NIH, James R. Gillette Award from the American Society for Pharmacology & Experimental Therapeutics, the Founders Award from the American Chemical Society Division of Chemical Toxicology and the ISSX North American Scientific Achievement Award, in Honor of Ronald W. Estabrook. He has been elected as a Fellow of the Royal Society of Chemistry, the Japanese Society for the Study of Xenobiotics, and the American Chemical Society.

We thank Tom for his service to our School and wish he and Kathleen the absolute best in their next adventures.

Do you want to study Medicinal Chemistry with globally-ranked researchers like Dean Emeritus Baillie? Click here to learn about MedChem and to apply

Link to Medicinal Chemistry archived news

Kelly M. Hines, Ph.D., senior fellow in the Department of Medicinal Chemistry (Libin Xu lab), is one of three recipients of the 2015-2016 Global Fellowship by the United States Pharmacopeial Convention (USP). This award, in the amount of $30,000, will support Dr. Hines’s project, using Ion Mobility-Mass Spectrometry (IM-MS) to screen standards of approximately 2,000 drug compounds available from the UW and create a database of drug purity information.

IM-MS is a rapid and orthoganal gas-phase separation technique based on molecular structures, requiring only milliseconds per analysis. The technique thus has several advantages over conventional liquid chromatography-based UV or MS methods: its rapid separation nature and determination of the structural information at the same time. Dr. Hines plans to use this technique to define the structure-mass relationship of drugs, excipients (extra material combined with the drug — e.g., to make a pill) and impurities, which would provide high-confidence identifications and purity assessments of drugs (including dietary supplements).

The USP is a scientific nonprofit organization that sets standards for the identity, strength, quality, and purity of medicines, food ingredients, and dietary supplements manufactured, distributed, and consumed worldwide. Dr. Hines’ USP mentor for this project is Shankari Shivaprasad, scientific liaison with USP’s Chemical Medicines Department.

Congratulations, Kelly, on this well-deserved award!

At a combined 2015 orientation event with the department of Pharmaceutics, Medicinal Chemistry chair Kent Kunze welcomed four new students into our graduate program: Modestas Filipavicius, Lorela Paco, Dylan Ross, and Eleanor Vane.  Pharmaceutics has four students entering their graduate program and one student entering their masters program.  Welcome, one and all!

Modestas Filipavicius was born in Lithuania, finished the International Baccalaureate at RCN United World College in Norway, and spent a year in Northern India teaching English and first aid.  He then earned his BA in both Chemistry and Biology at Macalester College (St. Paul, MN).  Modestas worked in Med Chem Associate Professor Kelly Lee’s lab this summer, investigating the HIV envelope glycoprotein expression.  His major research interest is the structural biology of viruses.

Lorela Paco was born in Athens, Greece and raised in Albania.  She attended the United World College in Trieste, Italy before earning her BA in Chemistry with a Biochemistry emphasis at Macalester College.  Lorela was a Mayo Clinic Innovations Scholar, working with a Mayo investigator on a new drug submission.  She was a summer student at the University of Arizona’s Department of Cellular and Molecular Medicine.  Lorela is interested in Cytochrome P450 research and the interface between chemistry and biology.

Dylan Ross is a Washington native, earning his BS in Biochemistry from the UW.  During that time he worked at PhaseRX, a local therapeutics company, where he performed a wide range of bioanalytical studies.  Dylan also worked with Med Chem Professor Bill Atkins on a chiral chromatographic resolution of glutathione conjugates of hydroxynonenal, and as a volunteer in Assistant Professor Abhi Nath’s lab.  He is interested in the basis of functional and catalytic promiscuity in drug-metabolizing enzymes.

Eleanor Vane graduated from Clarkson College in Potsdam, NY with a BS in Biomolecular Science and a 4.0 GPA.  She worked at Carnegie Mellon University, characterizing a promiscuous protein’s interaction with organic dyes for their use in a new fluorescence labeling scheme.  Eleanor was also an Amgen Scholar at UC Berkeley, and she entered the Biological Physics, Structure and Design program at UW in the fall of 2014.  Also in 2014, Eleanor was awarded a five-year Fellowship in the NSF Graduate Research Fellowship Program.  She has joined Abhi Nath’s lab as a grad student in Medicinal Chemistry. Eleanor’s major research interest is using single molecule and biophysical techniques to study peptide membrane interactions.

Best wishes to our latest Med Chem students as they begin the graduate program!

Apply to earn your Ph.D. in Medicinal Chemistry at the UW!

It was a summer of hard work and discovery for four undergrads who participated in the Pharmacological Science Summer Diversity Program (PSSDP).  Hector Caldera (Fort Lewis College), Brianna Morgan (Southern Oregon University), Monica Pengshung (Southern Oregon University), and Hannah Rudolph (Agnes Scott College) recently presented posters at Mary Gates Hall to wrap up their summer experience at the School of Pharmacy.

The PSSDP provides opportunities for talented undergraduate students from diverse social and cultural backgrounds to perform hands-on research in drug metabolism, pharmacokinetics, cellular pharmacology, molecular pharmacology, and biophysical virology.  Participants are selected from a national pool of applicants as well as current UW students.  Those selected receive a stipend, living accommodations, and a transportation allowance for the summer.  The host departments are Medicinal Chemistry, Pharmaceutics, and Pharmacology.

Monica Pengshun rotated with Professor Joanne Wang in Pharmaceutics. Her poster, “Substrate-dependent inhibitory effect of cimetidine and pyrimethamine on renal organic cation transporters OCT2 and MATE1,” focused on predicting drug-drug interactions that could alter the clearance of drugs and toxins from the kidneys.

Hector Caldera collected medicinal plants as a child, sparking an interest in chemistry.  “My summer project took me out of my comfort zone, from organic chemistry to molecular biology,” said Hector.  His poster, “Investigation of the Structure of Recombinantly Expressed Influenza M1 Matrix Protein,” reflects his research into a protein that plays a key role in the life cycle of the influenza virus.  Discovering how to disrupt the protein’s function could lead to new drug designs in the ongoing war against  influenza.  Hector’s faculty mentor was Medicinal Chemistry Associate Professor Kelly Lee.  “I really enjoyed the mixture of support and independence from my mentors,” said Hector. “But . . . I don’t know about being down in that basement.”

Brianna Morgan is a pre-med student and new to the lab environment.  “This experience opened my eyes about grad school and options I might not have had before,” said Brianna.  “It was a supportive team experience for me, and I learned new techniques for research.”  Her poster, “Inhibition of the Cholesterol Biosynthetic Pathway by Known Drugs,” discusses how certain drugs can interrupt the cholesterol biosynthesis pathway.  This inhibition effect may be a risk factor for neurodevelopmental disorders, such as autism, because cholesterol plays important roles in the development of the nervous system.  Brianna’s faculty mentor was Medicinal Chemistry Assistant Professor Libin Xu.

Hannah Rudolph rotated with Associate Professor Paul Phillips in Pharmacology.  We wish our 2015 Summer Diversity students all the best as they begin Fall Quarter in their respective colleges and universities!

Medicinal Chemistry graduate student Mark Benhaim (Lee lab) has been accepted into the NIH-supported Molecular Biophysics Training Program.  His proposed research thesis, “Deciphering the Antiviral Activity of Human Defensins: Inhibiting Influenza Virus Fusion,” won him a two-year tenure on this predoctoral training grant. Benhaim’s mentor, Med Chem Associate Professor Kelly Lee, will fund the research on this project and NIH will pay Benhaim a stipend, partial tuition, and a travel award.

Benhaim successfully completed a rigorous application process including a written research proposal and an interview during which he presented his proposal and answered questions.

Working in the Lee lab, Benhaim is studying how components of the innate immune system recognize and interact with enveloped viruses, specifically influenza virus. The innate immune system is the body’s first line of defense against infection. “My goal is to understand how these defensins, these small antimicrobial peptides, interact with viruses,” said Mark. “We know they prevent infections of diverse viruses like herpes simplex, influenza, and HIV, but very little is understood about how they work.”

The thrill of figuring out how things work is what brought Benhaim to science, and now into biophysics. “These proteins are such amazing molecular machines,” he said. “It just blows my mind how something so small is able to carry out such complex processes.”

“Mark’s studies will provide new mechanistic insight into the action of these important anti-pathogen components of our immune system,” said Dr. Kelly Lee, “and may eventually suggest new strategies for developing antiviral therapeutics.”

Congratulations, Mark!

Dennis Goulet (Atkins lab), graduate student in Medicinal Chemistry, is completing a summer internship with Janssen Pharmaceuticals, Inc., a Johnson & Johnson company headquartered in New Jersey. Janssen wanted someone with a background in biophysical characterization and an interest in antibody scaffolds (proteins that bring other proteins together for interaction); Goulet was selected via application and phone interview. The 13-week internship allows him to see pharmaceutical research from an industry perspective. “It’s fascinating to hear about the research people are working on, and to know any of these projects could produce a new agent to treat cancer and other diseases,” said Dennis.

At the Janssen research facility near Philadelphia, Pennsylvania, Goulet is making antibody constructs and labeling them for use in fluorescence experiments. “We’re interested in the advantages bispecific antibodies may have over traditional monoclonal antibodies for treating cancer,” said Dennis. (Bispecific antibodies are artificial proteins engineered to bind to two distinct biological targets.) By exploring the kinetics and thermodynamics of bispecific antibody assembly, scientists hope to speed up their formation and increase production efficiency to yield more antibodies for therapeutic use.

“It’s quite a collaborative environment,” said Dennis. What surprised him most was the level of support for novel ideas and perspectives. The wide range of scientific backgrounds at Janssen has made it possible for Goulet to explore new techniques and receive advice from experts in the field.

“I’m grateful to Dr. Atkins and Dr. Chiu (Associate Director at Janssen) for giving me this opportunity,” said Dennis, “and to the group at Janssen for making the internship such an informative and enjoyable experience.”

Congratulations, Dennis — see you in Seattle for Fall Quarter!

Medicinal Chemistry graduate student Mavis Li (Atkins lab) has received an award from the Hope Barnes Fellowship Fund. Hope Barnes was a Med Chem graduate student who died in a climbing accident in 1991. Hope’s family established The Hope Barnes Graduate Fellowship to support and encourage talented graduate students in medicinal chemistry. The Fund will pay Mavis’s stipend and tuition for summer and fall quarters 2015, in addition to a $1,000 recognition award.

Working in the Bill Atkins lab, Mavis is researching the structure and functions of p-glycoprotein (P-gp), a protein which acts as a drug transporter, pumping drugs out of cells in the body. Not enough is understood about the effect of P-gp on the bioavailability and effectiveness of certain drugs.

“I am grateful to benefit from the generosity of Hope Barnes’s family,” said Mavis. “This award will support my work with P-gp and how it affects the behavior of some important drugs that patients rely on.”

Congratulations, Mavis!

Cytochrome P450 enzymes are found in all living organisms and are essential in metabolizing a wide range of substances including steroids, fatty acids and the majority of pharmaceuticals. They control the elimination of most drugs and therefore strongly influence drug-drug interactions that can cause adverse side effects. P450s are also capable of detoxifying many environmental pollutants. In 1976, a small group of scientists gathered to share research about the mysterious enzyme at the center of all this biological action and reaction.

That informal gathering evolved to become the International Conference on Cytochrome P450 (CYP), a major bi-annual event with speakers from all over the world and an expanding range of subjects from basic biophysical research to applied aspects of toxicology and drug metabolism. The Medicinal Chemistry Department, led by professors Allan Rettie and Bill Atkins, hosted the Seattle conference in 2013. Drs. Rettie and Atkins also serve on the conference advisory committee.

Dr. Rettie and five students from Med Chem attended the 2015 conference in Tokyo, Japan earlier this summer. Eric Evangelista, Wynton McClary, Robert Pelletier, Ryan Seguin, and Nick Treuheit presented posters at the conference where Dr. Rettie was a featured speaker (“Drug Metabolism Contributions to the Development of Precision Medicine.”)

“Everyone at the conference was hospitable and welcoming,” said Nick Treuheit. “We got to interact with well-known people in the P450 field and experience the full range of experimentation that’s being done with it.”

“It was a terrific experience to talk with fellow P450 researchers from around the world,” said Ryan Seguin. Ryan was impressed by the variety and breadth of topics covered by the presenters. “Japan is an amazing place,” he added. “I enjoyed interacting with people and experiencing their culture.” Ryan tried local delicacies such as naga-imo (a slimy-textured grated mountain yam) and lived to tell about it, saying “it actually tastes pretty good, once you get past the texture.”

Robert Pelletier was excited to learn about a new way to “see enzymes work” using neutron crystallography, a technique which will play an important role in future drug development. He also enjoyed catching up with old friends and making new friends among the international students.

“It was fantastic hearing about the latest advances in our understanding of Cytochrome P450s,” said Wynton McClary. “And in our spare time we enjoyed Tokyo’s history and atmosphere.” Eric Evangelista agreed it was “a great learning opportunity, meeting with other scientists and discussing their research.”

The students also got helpful feedback on their own work during poster presentations. Ryan presented a new metabolite that may shed light on the metabolism of drugs that contain nitrogen. Robert’s poster dealt with the metabolism of Chlormethiazole, a drug used to treat acute alcohol withdrawal, and its effect on Cytochrome P450 enzyme activity in patients using the drug.

“The P450 conference was an illuminating experience for faculty and students alike,” said Dr. Rettie. “We are all looking forward to the 2017 conference in Dusseldorf, Germany.”

Ben Maldonato is busier than usual this summer. The Medicinal Chemistry grad student is one of the 2015 cohort of predoctoral students chosen to receive a summer TL1 grant from the Institute of Translational Health Sciences (ITHS). During this 3-month research experience, Ben is conducting independent research with faculty mentor Rheem Totah, attending an Interdisciplinary Clinical Research Methods Seminar, and participating in colloquia and informal gatherings throughout the UW health sciences community. He will generate a research abstract from his chosen project.

“I’m pretty new to the grant writing process, so I was surprised and excited to be selected,” said Ben.

The TL1 Predoctoral Multidisciplinary Clinical Research Summer Program is an expression of ITHS’s focus on moving scientific discovery quickly to its practical application in clinical and community settings. Participants receive a stipend, tuition for the seminar, and up to $400 for research expenses.

Ben’s research project involves the enzyme Thiol Methyltransferase (TMT), known to metabolize drugs such as Clopidogrel and Prasugrel (blood thinners), among others. Inconsistency in TMT activity may be the key to discovering the reason for the variety in adverse side effects observed when different people are given the same dosage of the drug.

“It’s a great feeling when your research idea is supported with an award,” said Ben. “I’m really grateful for this chance to work with Dr. Totah on research that could help reduce side effects for people who are using these types of drugs.”

Ben’s faculty mentor, Rheem Totah (Associate Professor of Medicinal Chemistry), commented, “I’m pleased to be working with Ben on this project. The goal of the TL1 program is to train clinician-scientists who can translate scientific discovery into practice more rapidly, for the benefit of patients in the northwest U.S. I know Ben will make the most of this opportunity and will have an impact on the field in the future.”

Congratulations, Ben, on this well-deserved honor!

Robert Pelletier left a career in industry to pursue his PhD in Medicinal Chemistry and follow his passion for teaching and research. The American Foundation for Pharmaceutical Education (AFPE) has recognized Pelletier’s potential for leadership, and awarded him their 2015 Pre-Doctoral Award in Pharmaceutical Science. The award period begins in September 2015. The stipend of $10,000 will support Pelletier’s research for his thesis project, “Mechanism of CYP2E1 Inhibition by Chlormethiazole.”

CYP2E1 is responsible for the metabolism of certain chemical compounds (i.e., as drugs or pesticides) that are toxic to humans. For example, CYP2E1 bioactivates the over-the-counter drug, acetaminophen, to a reactive, toxic metabolite called NAPQI. During an overdose, the amount of NAPQI formed overwhelms the liver, increasing the likelihood of liver damage or liver failure. Acetaminophen toxicity has replaced viral hepatitis as the most common cause of acute liver failure, according to a June 24, 2014 article in Medscape online.

Pelletier is examining chlormethiazole’s suitability as an inhibitor of CYP2E1’s ability to cause these toxic reactions. “We will be able to assess the application of chlormethiazole-mediated CYP2E1 inhibition in preclinical drug development,” notes Pelletier, “and in the possible mitigation of CYP2E1 bioactivation-mediated toxicity, such as that seen with acetaminophen overdose.”

Pelletier, a member of the Kunze Lab, submitted a research proposal to AFPE, along with recommendation letters and a Statement of Purpose. Reviewers were impressed with his extensive research experience, lab skills, and the soundness and relevance of the CYP2E1 project. “I’m so excited to receive this award,” said Pelletier. “I hope my work will lead to advances in addressing the growing issue of acetaminophen toxicity.”

Congratulations to Robert on this well-deserved award!
 

Link to Medicinal Chemistry archived news

LIBIN XU, Ph.D., is an Assistant Professor in the Department of Medicinal Chemistry. He graduated with a B.Sc. from Nakai University, Tianjin, China, completed his Ph.D. in Organic Chemistry at University of Illinois at Chicago, and was a Postdoctoral Fellow at Vanderbilt University. His current research focuses on investigating the role of 7-dehydrocholesterol (7-DHC)-derived oxysterols in the pathophysiology of Smith-Lemli-Opitz syndrome (a cholesterol biosynthesis disorder) and developing therapeutic approaches toward this disease and development of novel lipidomic approaches based on ion mobility-mass spectrometry.

Link to Medicinal Chemistry archived news

Dean Emeritus Thomas Baillie was recognized as one of the topmost cited researchers in the area of Pharmacology & Toxicology. The Thompson Reuters Highly Cited Researchers list identifies over three thousand researchers worldwide whose research was among the top 1% most cited for their subject field and year of publication. Baillie’s research focused on understanding the biochemical mechanisms involved in the metabolism of drugs to chemically reactive metabolites (“metabolic activation”). Many such reactive intermediates are toxic to the cells they encounter, and by gaining knowledge of the identities of these metabolites, it becomes possible to rationally alter the structure of the parent drug to avoid metabolic activation, and thereby design a safer medicine. “Much of this research began at UW when I was a faculty member before I went to the private sector,” said Baillie. “I collaborated with many colleagues here on this work, most especially Sid Nelson.”

Dr. Allan Rettie has decided to step down as Chair of the Department of Medicinal Chemistry, effective June 13, 2014, after serving the School for almost 15 years in that capacity. During this period, Dr. Rettie has effectively guided the department through many curricular and organizational changes, as well as economic challenges. “It is to his credit that Medicinal Chemistry is in as strong a position as it is today,” said Dean Thomas Baillie.

Dr. Rettie obtained a PhD in Pharmaceutical Sciences in 1983 from the University of Newcastle-upon-Tyne, England, before moving to Seattle to post-doc with Drs. Mont Juchau and Dr. Bill Trager at the UW in the areas of extrahepatic drug metabolism and metabolic drug-drug interactions, respectively. He joined the faculty of the UW School of Pharmacy in 1987 and became the Medicinal Chemistry Department Chair in 2000.

Dr. Rettie’s research interests have focused mainly on the human P450 enzymes and attempts to understand mechanisms of catalysis, substrate specificity, pharmacogenetic variability and adverse drug reactions related to these monooxygenases. He has published over 150 peer-reviewed papers and held research grants from the National Institutes of Health (NIH) in these topic areas for 24 years. Dr. Rettie has served on the editorial boards of Drug Metabolism and Disposition, Drug Metabolism Reviews, Journal of Pharmacology and Therapeutics, Current Drug Metabolism, and Chemico-Biological Interactions, as well as numerous NIH grant review panels.

Dr. Rettie will return to a regular faculty position this summer. “It has been a pleasure working with Allan as a member of the School’s Executive Committee,” said Dean Baillie. “I am grateful for his leadership and I hope everyone will join me in thanking him for his service as Chair.”

Link to Medicinal Chemistry archived news

The American Association of Colleges of Pharmacy (AACP) recently honored Dr. Brendan Stamper and his colleagues at the 2014 AACP annual meeting. Dr. Stamper is a former Med Chem graduate student who received his Ph.D. in 2010 and is now an Assistant Professor in the School of Pharmacy at Pacific University in Hillsboro, Oregon.

Dr. Stamper directed a team of university faculty and staff to develop an innovative series of tutorials that helps first-year pharmacy students learn about pharmaceutical sciences. This portfolio of tutorials was chosen as one of three national winners of the AACP’s 2014 Innovations in Teaching Competition. Dr. Stamper presented the curriculum at a special session during the AACP annual meeting in July.

Congratulations, Brendan, on this well-deserved honor!

Link to Medicinal Chemistry archived news

The Institute of Translational Health Sciences TL1 Multidisciplinary Predoctoral Clinical Research Training Grant is a year-long training experience funded by the National Institutes of Health and the National Center for Research Resources. The program allows grant recipients to work as part of an interdisciplinary team doing research that focuses on identifying major clinical problems, addressing these problems in the laboratory, and bringing bench discoveries into clinical practice. Eric Evangelista (Rheem Totah lab) has recently received funding from this predoctoral training grant.

“I’m very thankful to have received the TL1 training grant support,” said Eric. “The grant will allow me to further research aimed at understanding the role that the drug-metabolizing enzyme CYP2J2 plays in proper cardiac electrophysiology.”

Congratulations, Eric, and we wish you success in your research!

Link to Medicinal Chemistry archived news

Dr. Brianne Raccor, Senior Fellow in the Rheem Totah laboratory and a Elmer M. and Joy B. Plein Fellow, has taken a position as Assistant Professor in Pharmaceutical Sciences at Campbell University in Buies Creek, North Carolina. “I am delighted to be a new member of the faculty at Campbell,” said Brianne. “My excellent training in the Totah lab and my time as a Plein Fellow have prepared me well for a successful career in research and teaching.”

“We are excited for Brianne as she embarks on her new adventure,” said Associate Professor Rheem Totah. “Her infectious passion for science, troubleshooting abilities, and collegiality will be greatly missed.”

We congratulate Brianne and hope she will continue working with Med Chem on future projects in her new role.

Link to Medicinal Chemistry archived news

Nick Au, Jean Dinh, and Eri Nakatani-Webster wait for their moment on the stage during graduation exercises at Meany Hall. (Photograph courtesy of Meg Running.)

Congratulations to the following students, who received the Doctor of Philosophy in Medicinal Chemistry during commencement exercises held at Meany Hall on June 13, 2014:

Nicholas Au
Pharm.D. 2009, University of Washington
Dissertation: “Genetic and Environmental Factors Affecting Hemostasis in the Yup’ik.”

Jean C. Dinh
B.S. 2005, Pharm.D. 2009, University of Washington
Dissertation: “In Vitro and In Vivo Studies of Methadone Metabolism and Pharmacokinetics.”

Eri Nakatani-Webster
B.S. 2008, University of Arizona
Dissertation: “Controlled Assembly of Viral Surface Proteins into Biological Nanoparticles.”

Congratulations to this year’s graduates, and very best wishes as you go forth and Med Chem!

Link to Medicinal Chemistry archived news

The Department of Medicinal Chemistry is proud to congratulate alumnus Michael Adams, Ph.D. for his recent appointment as Dean of the College of Pharmacy & Health Sciences at Campbell University in Buies Creek, North Carolina. Michael did his graduate work in Medicinal Chemistry with the late Sid Nelson and graduated in 2003. His research interests focus on causes and mechanisms for prevention of drug-induced liver disease, with particular attention to xenobiotics that cause liver damage after metabolism.

We are happy to see Michael’s continued success and wish him well in his new role.

Link to Medicinal Chemistry archived news

Medicinal Chemistry graduate student Ryan Seguin (Kent Kunze lab) has been awarded the prestigious Magnuson Scholarship for 2014-2015. The University names six Magnuson Scholars annually, one from each of the health sciences schools. Awardees are selected based on their academic performance and potential contributions to health sciences research.

Ryan joined Dr. Kent Kunze’s lab in 2011 and was selected as a trainee on the NIH-sponsored Pharmacological Sciences Training Grant. Dr. Kunze noted, “Ryan has the motivation, work ethic, and creativity to become a successful independent academic scientist.” As a Magnuson Scholar, Ryan will focus on research that he hopes will lead to the discovery of novel therapeutics or unveil the basis for enigmatic health disorders with few or no treatment options currently available. “The main driving force,” said Ryan, “is always to improve health and quality of life for others, either directly through development of treatment options, or indirectly by enhancing our understanding of drug targets, design, and metabolism.” In addition, Ryan continues teaching, mentoring, and spreading knowledge and enthusiasm for science.

“It is such an honor to be selected for this award,” said Ryan, “and I am excited for the opportunity to further my research and career. I am grateful to the Department of Medicinal Chemistry for the continuous support, and to my advisor, Kent Kunze, for his relentless enthusiasm and encouragement.”

Congratulations to Ryan on this well-deserved award!

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Former Medicinal Chemistry postdoctoral fellow Klarissa Hardy has received a 2014 New Investigator Award from the American Association of Colleges of Pharmacy (AACP). Klarissa, now an Assistant Professor at Lipscomb University College of Pharmacy in Nashville, TN, was one of 17 award recipients for 2014. The New Investigator program provides start-up funding for new pharmacy faculty’s research programs. The awards are given to individual faculty starting their academic careers at ACPE-accredited colleges or universities in the U.S. Klarissa will receive $10,000 for her research project “Molecular Mechanisms of Drug-Induced Liver Injury by Tyrosine Kinase Inhibitors” as well as a travel award so she may present her findings at the AACP annual meeting in 2015.

“I am very pleased for Klarissa to have achieved this success so early in her faculty career,” said Dr. Allan Rettie, Chair of Medicinal Chemistry. “It is very well deserved.”

Klarissa was part of the late Dr. Sid Nelson’s lab at Med Chem, where she studied the targeted breast cancer drug, lapatinib, to examine the role of cytochrome P450-mediated metabolic activation in the liver toxicity associated with lapatinib. “My current work continues along these lines,” she said, “and is focused on two additional anti-cancer tyrosine kinase inhibitors — pazopanib and sunitinib — which have both been associated with hepatotoxicity.” The goal is to characterize the metabolism and bioactivation pathways of pazopanib and sunitinib to provide insight into the biochemical mechanisms of hepatotoxicity.

“I am excited and thankful to God for the opportunity to receive this award,” added Klarissa, “and I see it as an encouraging start to my career. I also thank my excellent mentors, Sid Nelson and Allan Rettie, who supported my postdoctoral training at UW to make this possible.”

Congratulations to Dr. Klarissa Hardy on this well-deserved award!

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The Department of Medicinal Chemistry welcomes Abhinav “Abhi” Nath, PhD, as its newest faculty member. Dr. Nath joins the department as an Assistant Professor, coming from Yale University where he did postdoctoral work in Molecular Biophysics and Biochemistry.

“We are very pleased to welcome Dr. Nath to Med Chem,” said Allan Rettie, PhD, professor and Chair of the department. “With a research career that spans biology, chemistry, and physics, Dr. Nath brings a diverse skillset to our department that will benefit our faculty and students. We are confident that Dr. Nath possesses the knowledge and skills necessary to further advance the work of Medicinal Chemistry at the School of Pharmacy. We are fortunate to have him as a member of our faculty.”

Dr. Nath received his Bachelor of Arts in Biology and Chemistry from the University of Virginia. He completed his doctorate in Medicinal Chemistry at the University of Washington, where his research focused on the mechanisms of substrate binding by Cytochrome P450s and other drug-metabolizing enzymes. He went on to Yale University, where he was an American Heart Association Postdoctoral Fellow studying intrinsically disordered and amyloid-forming proteins using single-molecule fluorescence and computational methods.

Abhi Nath’s lab in the department of Medicinal Chemistry will focus on understanding the roles of protein dynamics in neurodegenerative disease, drug metabolism, and the body’s response to oxidative stress. “We are interested in developing new ways to study highly dynamic proteins, and to control their behavior in therapeutically useful ways,” said Dr. Nath. “To this end, we will use a broad range of experimental and theoretical approaches from biochemistry, biophysics, and pharmacology.” Systems of interest will include the Glutathione-S-Transferase enzyme superfamily (involved in drug metabolism and the oxidative stress response) and the intrinsically disordered protein Tau (implicated in Alzheimer’s disease and pathology resulting from traumatic brain injury).

“I’m thrilled to be back in Seattle and at the UW,” said Dr. Nath. “Medicinal Chemistry’s tight-knit and welcoming community and its tradition of excellence in research make it an outstanding environment for me to establish my lab and independent scientific program. I am eager to contribute to the department’s research and training missions, and to work closely with the exceptional staff, students, and faculty of the School of Pharmacy and the broader UW community, as I do so.”

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Dr. William Atkins has been named the first Sid Nelson Endowed Professor in Medicinal Chemistry. Bill joined the Med Chem faculty in 1991. His research focuses on the biochemical nature of detoxification enzymes and on drug metabolism, with emphasis on biophysical mechanisms. He has been awarded several NIH grants for his research on enzyme systems. His lab also focuses on characterization of nanoparticles for drug delivery and targeted therapy.

“I am honored to receive this professorship, which is really a tribute to Sid’s life and work,” said Bill with typical modesty. “I hope our work in the lab will be a credit to his legacy.”

Sid Nelson was Dean Emeritus of the School of Pharmacy, and a Professor of Medicinal Chemistry. He passed away suddenly in December 2011. The Sid Nelson Memorial Fund, an expression of both grief and regard for Sid, was built with contributions from family, friends, colleagues, together with donations from private industry. The memorial fund later became the Nelson Endowed Professorship; Bill, who was a colleague and co-author with Sid over the years, is its inaugural recipient.

Allan Rettie, Professor and Chairman of Medicinal Chemistry, said: “This is the first named Professorship in the Department of Medicinal Chemistry. That’s an exciting development for us, and Bill is a most worthy recipient.”

School of Pharmacy Dean Tom Baillie said of Bill, “He possesses the devotion to research and education that were the hallmarks of Sid’s career.”

That’s high praise indeed, and we, his colleagues in Med Chem, couldn’t agree more. Congratulations, Bill!

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Med Chem student Nick Au (Allan Rettie lab) was recently part of a team of UW graduate students who won a “Best Innovation Idea” prize in the 16th annual UW Business Plan Competition. The team is developing a “smart” polymer contact lens as an alternative delivery platform for people with diabetes.

The UW Business Plan Competition is produced by the Buerk Center for Entrepreneurship at the Foster School of Business. They awarded $68,220 in seed funding to winners of the 2013 competition.

Nick, congratulations on your win!

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Carlos is camera-shy, but Nanci Murphy makes great cookies!

Dr. Carlos Catalano, Professor in Medicinal Chemistry, was awarded a Volunteer Recognition Award during the Health Sciences Center’s annual Martin Luther King, Jr. celebration on January 17 in the HSB lobby. The award winners are named by the UW Health Sciences deans.

Among other community commitments, Dr. Catalano has been instrumental in facilitating the Pharmacological Sciences Summer Diversity Program, which provides research opportunities for talented undergraduate students from diverse social and cultural backgrounds. He also serves as faculty adviser for UW’s chapter of the Society for the Advancement of Chicanos and Native Americans in Science (SACNAS). Started in 2007 with just five members, SACNAS at UW won Chapter of the Year in 2011 and hosted the national conference in 2012. Dr. Catalano says his role as adviser is mostly to “stay out of the way,” but we know better.

Congratulations, Carlos, and thanks for your dedication to our students!

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In a fitting tribute to our late colleague, mentor and friend, the School of Pharmacy is humbled to share that we have formally established the Sid Nelson Endowed Professorship in Drug Metabolism. The seeds for the professorship were sown in December 2011, after our much-loved professor of medicinal chemistry and dean emeritus passed away suddenly. Our community rallied together to honor Sid’s life and contributions to the School by creating the Sid Nelson Memorial Fund. The memorial fund later became the Endowed Nelson Professorship — a fund that we hope to eventually turn into a more substantial endowed fund in honor of Sid.

The recipient of this professorship is a distinguished faculty member in the field of drug metabolism — Professor of Medicinal Chemistry Bill Atkins (pictured at left). Bill Atkins earned his bachelor’s in chemistry with honors from The College of William & Mary, his master’s in pharmacology from Harvard University and his PhD in biochemistry from the University of Illinois at Urbana-Champaign. From 1988 to 1991, he performed postdoctoral research in the Department of Chemistry at The Pennsylvania State University as a National Institutes of Health Kirschstein Fellow.

He has been on our Department of Medicinal Chemistry faculty since 1991. His research focuses on the biochemical nature of detoxification enzymes and on drug metabolism, with emphasis on biophysical mechanisms. He has been awarded NIH grants for research on several enzyme systems. Recent research also includes characterization of nanoparticles for drug delivery and targeted therapy.

“This is the first named professorship to be established in the Department of Medicinal Chemistry,” said Dean Tom Baillie. “I am delighted that we can pay tribute to Sid in this way thanks to the generosity of our donors.”

Baillie also notes that Atkins, who was a colleague of and co-author with Nelson for two decades, will carry on Nelson’s legacy well. He possesses the devotion to research and education that were hallmarks of Sid’s career. For his part, Bill Atkins is honored to be the inaugural recipient of this professorship that pays tribute to the life and work of a friend who we all miss deeply.

Read more about Sid Nelson’s life and legacy.

~May 7, 2013

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The Lee lab, L-R: Long Gui, Mike Guttman, Natalie Garcia, and Tad Davenport, discuss membrane fusion at a recent conference in Whistler, B.C.   Missing: Kelly Lee (or is he??)

Dr. Kelly Lee, Assistant Professor of Medicinal Chemistry, has been awarded a $1.45 million grant from the National Institutes of Health to study some of the more elusive but fundamental aspects of influenza virus membrane fusion. Dr. Lee will focus on determining what drives the fusion process, in addition to the nature of membrane deformations during fusion, which currently is not well understood.

Using electron cryotomography, small-angle X-ray scattering with 3-D shape reconstruction, and Hydrogen-Deuterium exchange with mass spectrometry analysis, the Lee lab will study the interplay between the hemagglutinin fusion protein, the viral matrix layer, and host cell membranes during fusion of the influenza virus with the host. In addition, through a variety of collaborations, the Lee lab is starting to investigate the mechanism of action of small molecule compounds that inhibit the fusion process.

“We’re delighted to have received the NIH support, and look forward to learning a lot about the fundamental physical event, protein-mediated membrane fusion, that underlies cell invasion by an important human pathogen,” said Kelly.

Congratulations to Kelly and the Lee lab on receiving support for this exciting research!

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Eri Nakatani Awarded Magnuson Scholarship

Med Chem graduate student Eri Nakatani (Carlos Catalano lab) has been awarded the prestigious Magnuson Scholarship for 2012. The University names six Magnuson Scholars annually, one from each of the health sciences schools.  Awardees are selected on the basis of academic performance and potential contributions to health sciences research.

As a Magnuson Scholar, Eri will focus on developing therapeutic nanoparticles derived from viral proteins. Her work involves the incorporation of an HIV-1 surface glycoprotein (gp160) into a water soluble, nanoscale lipid bilayer system (nanodiscs), which might someday be useful as an HIV vaccine. The project is a collaborative one involving the Catalano lab, Dr. Shiu-Lok Hu (Pharmaceutics), and Dr. Bill Atkins (Med Chem).

In addition, Eri is working on the thermodynamic characterization of the bacteriophage lambda capsid maturation process in vitro, under the guidance of Dr. Carlos Catalano, and with assistance from Dr. Kelly Lee (Med Chem). “Lambda virus has utility here as a model system for herpes viruses, but we also hope to use it as a platform for the development of targeted nanoparticles for use in therapeutics and/or diagnostics,” Eri said.

“I am so honored to have received this opportunity to take my research to a new level and broaden my scientific horizons,” said Eri. “I look forward to continuing my work on nanoparticle therapeutics and hope to obtain valuable feedback at conferences I might otherwise have been unable to attend.”

Congratulations, Eri!

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Last year, the director of the UW School of Pharmacy Mass Spectrometry Center, Dave Goodlett, developed a method to make mass spectrometry research easier. The method, known as Surface Acoustic Wave Nebulization (SAWN), simplifies how researchers introduce nonvolatile compounds — such as proteins, lipids and small molecules like caffeine — into a mass spectrometer for analysis. Historically, researchers working with nonvolatile samples had to choose between methods that are easy to perform or that perform well. The SAWN method (pictured at left) combines ease of use with high performance.

With the help of the UW Center for Commercialization (C4C), Goodlett and Dr. Patrick Langridge-Smith of the University of Edinburgh have formed a company, Deurion LLC, to further develop this technology and make it commercially available. In December, Deurion received a $150,000 National Science Foundation grant to continue its work. This grant builds on a UW C4C Gap Fund of $50,000 that Goodlett received last summer to construct a prototype SAWN device.

UW postdoctoral fellows Scott Edgar and Sung Hwan Yoon, members of the Goodlett Lab, are currently working as scientists with Deurion. Edgar is the manager and senior scientist responsible for managing the commercialization of the SAWN technology. Among other things, he and Yoon are writing an interface and developing the wiring system that will allow scientists to plug their laptop into the mass spectrometer and run the SAWN method from their laptop. They’re also working to increase the sensitivity of the method — detecting smaller and smaller amounts of material.

Surface acoustic wave technology was invented in the 1960s and is used today in applications including electronic filters or sensors. However, the technology for ionizing samples specifically for mass spectrometry is a recent development.

Goodlett’s long-term goal for his company is for the new technology to be adopted by mass spectrometry research centers throughout the country. The SAWN method is so easy to use that practically anyone could master it in a few minutes, according to Goodlett. Improving the performance and ease of mass spectrometry will benefit scientists across disciplines — including in the life sciences, the pharmaceutical industry and homeland defense as well as those working in clinical research.

Mass spectrometers also play an important role in an area of investigation popularized by several TV shows in recent years — crime scene investigation. “Mass spectrometers are constantly seen on crime lab shows,” said Goodlett. “These instruments are used to detect explosives or drugs in someone’s system in a crime scene. If the SAWN method became a standard practice, it could speed up important analysis in a crime lab.”

Goodlett and his team are currently in the process of creating a scientific advisory board for Deurion. In addition, they are applying for a Phase 2 National Science Foundation grant to extend funding for another two years. UW C4C has also secured the intellectual property rights to the SAWN method and filed a patent application.

This is not the first start-up company to have spun off from work conducted at the School of Pharmacy. In the past decade, faculty research has also led to the creation of the Department of Pharmaceutics’ Drug Interaction Database and the Seattle biotech company Impel Neuropharma, co-founded by Professor of Pharmaceutics Rodney Ho and alumnus John Hoekman, PhD, ’10. Further, individual faculty members have made many discoveries over the years that have resulted in intellectual property rights.

While Goodlett is excited about this new undertaking, he’s also realistic about the challenges and unknowns ahead. Regardless, he said, “I am learning a lot. I am also glad that this company is providing such a great opportunity for my postdocs.”

Indeed, postdoctoral fellow Scott Edgar is the principal investigator on the NSF grant.

“This is unusual in academia because universities don’t allow postdocs to write their own grants,” said Goodlett. “But because the grant was on behalf of our company, Scott has been able to successfully write and manage the grant. No matter what happens, that will be a great thing for him to have on his CV.”

To see footage of the SAWN method, click here.

~March 9, 2012

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By Dean Emeritus Sid Nelson

Professor and Chair Emeritus of Medicinal Chemistry William “Bill” Trager lost his short battle to cancer last month. He was 72 years old.

Bill received his Ph.D. in medicinal chemistry — focusing on conformational analysis and nuclear magnetic resonance — from the University of Washington in 1965 under the supervision of the recently deceased Professor Alain Huitric. Bill went on to do his postdoctoral studies at the Chelsea School of Science and Technology in London, studying alkaloid structures with Sir Arnold Beckett.

In 1967, he joined the faculty of the University of California-San Francisco School of Pharmacy as an assistant professor of medicinal chemistry. While at UCSF, he acted as director of the high-resolution mass spectrometry center. That is where his interest in drug metabolism — which would be the focus of his life’s research — began.

In 1972, Bill was recruited back to the UW School of Pharmacy to be a professor of medicinal chemistry. He was the chair of the department from 1980 to 1983. He also served as an adjunct professor in the UW Department of Chemistry.

Bill was an outstanding, encouraging mentor to 22 graduate students and 12 postdoctoral fellows. I was one of his first graduate students, and I found him to have a quick wit and to be one of the most insightful and enthusiastic scientists I had ever met. He served as my mentor throughout my career. I might have been his administrative boss when I was Dean of the School of Pharmacy, but I continued to seek his sage advice throughout those years.

During his career, Bill published more than 200 research papers and was a co-author of two books. He was internationally renowned for his work on warfarin metabolism and mechanisms of warfarin drug interactions. He also was the principal investigator for nearly 20 years of a National Institutes of Health Program Project Grant for investigating drug interactions. Bill received the Alumnus of the Year Award from the UW School of Pharmacy in 2001, and he remained with the University of Washington until his retirement in 2004.

As an alumnus and emeritus faculty member, Bill stayed active with the School of Pharmacy, its faculty and staff. He and his wife, Caryl, recently created a fund that supports graduate students in medicinal chemistry, and his former graduate students and friends created the Drug Metabolism Endowed Graduate Fellowship in his honor.

As a man who was known for his sense of humor, collegial nature and keen intellect, it is hard to measure the impact he had on all those who worked with him and who had him as an adviser.

Bill was responsible for recruiting Dean Thomas Baillie when he first joined the UW faculty in 1981.

As Tom and I reminisced about Bill recently, Tom shared that when he first met Bill, he was immediately impressed by Bill’s personal warmth and sincerity, and he says he “soon came to know him as an outstanding scientist, a wonderful colleague, a valued mentor, and a kind and compassionate human being.”

He also fondly remembers Bill’s perennially cluttered office and his propensity to dress in casual attire. In fact, he spent much of the 1980s wearing his favorite pale blue sweater.

“Yet,” said Tom, “underlying his casual appearance was an ultra-sharp scientific mind that invariably came up with the key questions that needed to be answered.“

That scientific prowess opened the door for many scholarly appointments throughout his career. Among them, Bill acted as the American editor of the journal Chirality, science adviser to the Seattle district of the Food and Drug Administration, and committee member of the Pharmacological Sciences Review Committee of the National Institutes of General Medical Sciences.

If I were to sum up Bill Trager in a single word, it would be “genuine.” He greeted people with a wonderful smile, and I always felt genuinely welcomed by him no matter what the circumstances. He always spoke of his family, friends, colleagues and students with genuine pride and love.

The School of Pharmacy and the wider research community have lost a brilliant mind and a kind soul. He will be sorely missed.

He is survived by his loving wife of 25 years, Caryl, and seven children from his blended family.

Gifts can be made in Dr. Trager’s honor to the Bill Trager Drug Metabolism Endowed Graduate Fellowship Fund. To make a gift, click here or contact the School of Pharmacy Office of Advancement at (206) 616-3217 or rxgiving@uw.edu.

~December 3, 2009

By Bill Trager

Alain Huitric, professor emeritus of medicinal chemistry, passed away in late July at his home in Brittany, France, shortly before his 97th birthday.

Al was born in 1912 in Sainte Rose du Lac, a small French-Canadian community in the province of Manitoba. In his teens, he and his family immigrated to the United States and took up residence in Los Angeles.

He served in the United States Navy during World War II and upon his discharge, he used the G.I. Bill to further his education. He obtained his bachelor of science in chemistry from the University of San Francisco and his Ph.D. in medicinal chemistry from the University of California, San Francisco.

Al joined the faculty of the School of Pharmacy at the UW in 1955 where he remained for the rest of his career, retiring in 1978. He was the first School of Pharmacy faculty member to secure National Institutes of Health funding for research programs.

In the late 1950s and early 1960s, nuclear magnetic resonance was in its infancy. Al recognized its unique potential for solving thorny problems of structural organic chemistry, and it became the primary research tool in the dissertations of virtually all of his Ph.D. students. Training in this state-of-the-art technique opened doors for their further career development.

A quiet and gentle man, he was foremost a man of integrity. Al not only embodied the qualities of integrity — sound moral principles, honesty and sincerity — he exuded them. The power of his integrity commanded respect and had a profound influence on the lives of many, myself and Dean Emeritus Sid Nelson included.

Indeed, Dean Emeritus Nelson credits Al with inspiring him to pursue the path of teaching and research. He also says that, without Al’s “gentle nudge and huge vote of confidence,” he never could have become the dean of the School of Pharmacy.

And so Al’s legacy has been carried on through the many accomplishments of those of us who were his students. This also includes the president and CEO of a Fortune 500 chemical company as well as prominent researchers and professors at major universities.

But perhaps most importantly, his legacy is carried on through so many other people whose lives have been enriched simply by having known him.

Al is survived by his wife, Simone. After being a bachelor for most of his adult life, he met Simone on a trip to Brittany — the birthplace of his parents — in 1963. They soon married and a few years after his retirement, they returned to their roots and settled permanently in Brittany.

Al, we miss you.

Bill Trager received his Ph.D. in medicinal chemistry under the direction of Dr. Huitric at the University of Washington in 1972. He is professor emeritus of medicinal chemistry in the School of Pharmacy, and he served as chair of the department from 1980 to 1983.

Gifts can be made in Dr. Huitric’s honor to the UW School of Pharmacy Dean’s Fund for Excellence. To give, visit this page or contact the School of Pharmacy Office of Advancement at (206) 616-3217, rxgiving@uw.edu

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Valerie Daggett, professor of medicinal chemistry at UW School of Pharmacy, has received one of three Innovative and Novel Computational Impact on Theory and Experiment (INCITE) awards for her research in “Molecular Dynameomics.” This award, given by the US Department of Energy (DOE) provides Daggett the use of 2 million processor hours on the DOE’s IBM supercomputer housed at the National Energy Research Scientific Computing (NERSC) Center in Berkeley, California, to further her studies in protein folding with the aim of deciphering genetic information.

Daggett’s research focuses on realistic molecular modeling studies relating to protein stability, function, and folding. She and her team of researchers, use computer simulation methods to study the approximately 1,130 known, non-redundant protein folds. Up until this point, her team has been able to simulate about 30 of these folds. The supercomputer, which contains over 6500 processors, will enable Daggett and her team to take their study to a new level. By running the hundreds upon hundreds of slightly different simulations supported by the supercomputer, Daggett will create an extensive repository of molecular dynamics structures for protein folds, including the unfolding pathways. In addition, the control native simulations will be used in drug design studies.

“We are excited about the massive resources to which we now have access,” says Daggett. “The supercomputer will enable us to do in a month and half what would take several lifetimes on a single processor.”

Although much is known of the structural details of the native folded conformation of proteins, very little is known about the actual folding process. An understanding of protein folding has important implications for all biological processes, including protein degradation, protein translocation, aging, and human diseases, including cancer and amyloid diseases. Daggett’s research combined with the computing power of the supercomputer make this award an instrumental step towards advancing our knowledge of how proteins express genetic information and the medical advances such knowledge enables.

Current market value for processing time is $1 per hour. In addition to processing time, award winners will receive technical support and data storage privileges. This translates Daggett’s award in a monetary value of well over $2 million. In addition to the DOE award, Daggett has recently received a $25,000 Microsoft SciData Award for her project Dynameomics: Internet database and Web portal for molecular dynamics simulations of proteins.

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Dr. Allan Rettie, professor and chair of medicinal chemistry in the UW School of Pharmacy, Dr. Mark Rieder, research assistant professor in genomic sciences and their colleagues have identified a major genetic factor responsible for variability in patient responses to the commonly prescribed coumarin-based anticoagulant known as Warfarin. Warfarin, used to prevent harmful clotting after a heart attack, stroke or major surgery, is thought to be taken by over two million people a day in the US alone, yet dosage needs vary considerably between patients resulting in a challenge for their physicians. Rettie and his colleague’s research, supported by NIH funding, in genetic variation and the relationship this has to drug and dosage needs may enable physicians and pharmacists to more precisely medicate, thereby eliminating the negative effects of over- or under-medication. This field of study, known as Pharmacogenetics, is an important scientific pursuit at the forefront of the advancement of medical care. Read more about Rettie’s research in the June 2, issue of The New England Journal of Medicine or click on NPR interview.

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