{"id":16428,"date":"2016-10-26T16:42:23","date_gmt":"2016-10-26T23:42:23","guid":{"rendered":"https:\/\/sop.washington.edu\/?p=16428"},"modified":"2026-04-01T13:38:19","modified_gmt":"2026-04-01T20:38:19","slug":"sid-nelsons-legacy-lives-on-in-science-and-collaboration","status":"publish","type":"post","link":"https:\/\/staff.washington.edu\/twentzel\/wordpress\/sid-nelsons-legacy-lives-on-in-science-and-collaboration\/","title":{"rendered":"Sid Nelson\u2019s legacy lives on in science and collaboration"},"content":{"rendered":"
\n
\"Former
Former SOP First Lady Joan Nelson with Sid Nelson Endowed Professor of Medicinal Chemistry, Bill Atkins Photo: Alex Levine<\/span><\/figcaption><\/figure>\n

Busulfan is one of our oldest anticancer drugs. Today, it is often used to prepare a patient\u2019s body for a bone marrow transplant (hematopoietic cell transplant [HCT]) to fight various cancers. Busulfan kills some of the patient\u2019s blood cells to ensure the donor cells will be accepted.<\/p>\n

But busulfan is toxic.<\/p>\n

The work to mitigate that toxicity has become central in three labs across UWSOP\u2014a collaboration that would have brought cheer to the late Dean Sid Nelson. \u201cSid was fascinated by the biological and toxicological implications of chemistry,\u201d shared Bill Atkins.<\/p>\n

\n

“Busulfan is a \u2018goldilocks\u2019 drug.\u00a0The dosing has to be just right.\u201d
\n–Jeannine McCune, Professor of Pharmacy<\/p>\n<\/blockquote>\n

\"Pharmacy
Pharmacy Professor Jeannine McCune <\/figcaption><\/figure>\n

The collaboration began when Pharmacy Professor Jeannine McCune reached out to Bill in Medicinal Chemistry. For twenty years, Jeannine has studied the effects of busulfan on HCT patients to improve its efficacy and lower its toxicity. \u201c She approached Bill about using metabolomics, a new field that characterizes the small molecule metabolites in biological systems. She asked him to look at the data because of his expertise in the protective molecule glutathione, an antioxidant. (Glutathione is important to busulfan because it is metabolized by the glutathione S-transferases.)<\/p>\n

\n

\u201cSid might have called it \u2018strange chemistry.\u2019 Normally when a toxic drug modifies a protein, the drug stays around which makes it toxic\u2014but busulfan modified a protein and then disappeared. It\u2019s really awesome! I kept wondering why no one had studied this before.\u201d
\n–Bill Atkins, Sid Nelson Endowed Professor of Medicinal Chemistry<\/p>\n<\/blockquote>\n

\"Former
Former UWSOP Dean, Sid Nelson <\/figcaption><\/figure>\n

Bill saw the potential for novel protein modifications. In some classic cases, including examples studied by Sid, drugs or their metabolites are toxic because they stick on to proteins covalently. But with busulfan, it reacts with the proteins, changes them, and then disappears\u2014having changed the chemical nature of the protein. \u201cTo my knowledge, it\u2019s unprecedented,\u201d said Bill.<\/p>\n

Busulfan converts cysteines in proteins into dehydroalanine. These reactions also may have utility in protein engineering or nanotechnology. \u201cIf you could get other things to react with the dehydroalanine, you could expand how proteins are used\u2014including application of functional probes, drugs, or targeting moieties.\u201d<\/p>\n

\n

“Busulfan is a legacy drug, with a mechanism of action based on World War I chemical warfare agents, but it\u2019s still a frontline drug in pediatric cancer therapy,\u201d
\n—\u00a0Ed Kelly, Associate Professor of Pharmaceutics<\/p>\n<\/blockquote>\n

\"Associate
Associate Professor of Pharmaceutics Ed Kelly <\/figcaption><\/figure>\n

The collaboration has expanded. Understanding the toxicity of busulfan led Jeannine and Bill to Ed Kelly in Pharmaceutics, whose work with the organ on a chip project is making him a leader in Toxicology. Ed is working to create a liver on a chip that integrates vascular cells so they can start identifying pathways, proteomics, metabolomics, and chemistry, specifically for busulfan toxicity in this example.<\/p>\n

Jeannine, Bill, and Yvonne Lin (Associate Professor in Pharmaceutics) have an ongoing NIH R01 grant trying to improve the efficacy and lower the toxicity of busulfan. The team is eager to continue this project which embodies the collaborative spirit and science that were hallmarks of Sid\u2019s leadership.<\/p>\n<\/div>\n

\n

Advance your career in research or\u00a0pharmacy at the University of Washington!<\/h4>\n

Click on the links for\u00a0more information about our\u00a0Graduate Programs in Medicinal Chemistry, Pharmaceutics, Pharmaceutical Outcomes Research and Policy, and Biomedical Regulatory Affairs.<\/a><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Busulfan is one of our oldest anticancer drugs. Today, it is often used to prepare a patient\u2019s body for a bone marrow transplant (hematopoietic cell transplant [HCT]) to fight various cancers. Busulfan kills some of…<\/p>\n","protected":false},"author":3,"featured_media":16509,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[32,33,34,31],"tags":[],"class_list":["post-16428","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medchem-news","category-pceut-news","category-pharmacy-news","category-sop-news"],"yoast_head":"\nSid Nelson\u2019s legacy lives on in science and collaboration - School of Pharmacy<\/title>\n<meta name=\"description\" content=\"Busulfan is one of our oldest anticancer drugs. 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