Andy Hoofnagle MD PhD

Academic Title
Hospital positions
Head, Division of Clinical Chemistry
Director, Clinical Mass Spectrometry
Assistant Director, Clinical Immunology
Director, Nutrition and Obesity Research Center, Analytical Core

Andrew Hoofnagle

How to reach me

Mailing address:
Andrew N. Hoofnagle, MD, PhD
Department of Lab Medicine
Campus Box 357110
University of Washington
Seattle, WA 98195-7110

Courier address:
Department of Lab Medicine
1959 NE Pacific St,
Room NW120
University of Washington
Seattle, WA 98195-7110

Main office: (206) 598-6131
Fax: (206) 598-6189

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Research Interests

There are three main directions of research in our laboratory. The first investigates the interaction of inflammation and lipid metabolism using proteomics, mouse models, and cell-based methods. In addition, we are developing novel high-throughput immunoassays and quantitative mass spectrometric assays for biomarker validation in large studies. The second is the developmnent of clinical laboratory tests using liquid-chromatography/tandem mass spectrometry. Initially we are attempting to clinically translate peptide immunoaffinity methodologies to the detection in serum of the tumor marker thyroglobulin, the best marker we have for differentiated thyroid carcinoma. Lastly, we use informatics and data mining to develop useful benchmarks from large datasets of common laboratory tests to evaluate medical interventions throughout the hospital to optimize patient care and to ensure patient safety.

Available instrumentation and expertise

The Department of Laboratory Medicine can provide high-throughput analysis of human or animal specimens using LC-MS/MS. Currently, assays available include 25-hydroxy vitamins D2 and D3, 24,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D, the epimer of 25-hydroxyvitamin D3, plasma metanephrines, a panel of arginine and its metabolites including arginine, ornithine, citrulline, ADMA, and SDMA, a panel of opioids and their metabolites in urine, and the immunosuppresants methotrexate, cyclosporin, tacrolimus, and sirolimus. We are interested in working with other researchers in generating new assays with potential clinical utility. The unique workflow available through Research Testing Services and the Nutrition and Obesity Research Center make it easy to utilize the following instrumentation:

- Three Waters Quattro Micro mass analyzers equipped with 2795 autosampler-HPLC units
- A Waters Quattro Micro with an Acquity ultra-high pressure liquid chromotography front end
- A Waters Xevo TQ mass analyzer equipped with an Acquity
- An Applied Biosystems API 4000 Q-TRAP with either
  normal flow (Shimadzu) or nanoflow (Eksigent) capability.

Other mass spectrometry at UW:

Mike MacCoss's Lab

Jim Bruce's Lab

Medicinal Chemistry Mass Spectrometry Center

Diabetes Research Center Proteomics Core

Proteomics at the Fred Hutchinson Cancer Research Center

Chemistry Department Core

Matt Bush's Lab

Mandy Paulovich's Lab

UW Proteomics Resource

Selected publications

Henderson CM, Lutsey PL, Misialek JR, Laha TJ, Selvin E, Eckfeldt JH, and Hoofnagle AN. (2016) Measurement by a Novel LC-MS/MS Methodology Reveals Similar Serum Concentrations of Vitamin D-Binding Protein in Blacks and Whites. Clin Chem. 62(1):179-87.

Marsillach J, Becker JO, Vaisar T, Hahn BH, Brunzell JD, Furlong CE, de Boer IH, McMahon MA, Hoofnagle AN; and DCCT/EDIC Research Group. (2015) Paraoxonase-3 Is Depleted from the High-Density Lipoproteins of Autoimmune Disease Patients with Subclinical Atherosclerosis. J Proteome Res. 14(5):2046-54.

Grant RP and Hoofnagle AN. (2014) From Lost in Translation to Paradise Found: Enabling Protein Biomarker Method Transfer by Use of Mass Spectrometry. Clin Chem. 60(7):941-4.

Cox HD, Lopes F, Woldemariam GA, Becker JO, Parkin MC, Thomas A, Butch AW, Cowan DA, Thevis M, Bowers LD, and Hoofnagle AN. (2013) Inter-laboratory Agreement of Insulin-like Growth Factor-1 Concentrations Measured by Mass Spectrometry. Clin Chem. 60(3):541-8.

Hoofnagle AN, Becker JO, Oda MN, Cavigiolio G, Mayer P, and Vaisar T (2012) Multiple Reaction Monitoring-Mass Spectrometric Assays Can Accurately Measure the Relative Protein Abundance in Complex Mixtures. Clin Chem. 58:777-81.

Laha TJ, Strathmann FG, Wang Z, de Boer IH, Thummel KE, and Hoofnagle AN. (2012) Characterizing Antibody Cross-Reactivity for Immunoaffinity Purification of Analytes prior to Multiplexed Liquid Chromatography-Tandem Mass Spectrometry. Clin Chem. 58:1711-6.

de Boer IH, Sachs MC, Cleary PA, Hoofnagle AN, Lachin JM, Molitch ME, Steffes MW, Sun W, Zinman B, and Brunzell JD; for The Diabetes Control and Complication Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group. (2012) Circulating Vitamin D Metabolites and Kidney Disease in Type 1 Diabetes. J Clin Endocrinol Metab. 97:4780-4788.

Dickerson JA, Laha TJ, Pagano MB, O'Donnell BR, and Hoofnagle AN. (2012) Improved Detection of Opioid Use in Chronic Pain Patients through Monitoring of Opioid Glucuronides in Urine. J Anal Toxicol. 36:541-7.

Hoofnagle AN, Becker JO, Oda MN, Cavigiolio G, Mayer P, and Vaisar T (2012) Multiple Reaction Monitoring-Mass Spectrometric Assays Can Accurately Measure the Relative Protein Abundance in Complex Mixtures. Clin Chem. 58:777-81.

Brown CM, Becker JO, Wise PM, and Hoofnagle AN. (2011) Simultaneous Determination of 6 L-Arginine Metabolites in Human and Mouse Plasma by Using Hydrophilic-Interaction Chromatography and Electrospray Tandem Mass Spectrometry. Clin Chem. 57:701-9.

Hoofnagle AN, Laha TJ, and Laha TF. (2010) A Rubber Transfer Gasket to Improve the Throughput of Liquid-liquid Extraction in 96-well Plates: Application to Vitamin D Testing. J Chromatogr B Analyt Technol Biomed Life Sci. 878:1639-42.

Hoofnagle AN. (2010) Quantitative Clinical Proteomics by LC-MS/MS: Assessing the Platform. Clin Chem. 56: 161-4.

Hoofnagle AN, Wener MH. (2009) The fundamental flaws of immunoassays and potential solutions using tandem mass spectrometry. J Immunol Methods. 347:3-11.

Hoofnagle AN, Heinecke JW. (2009) Lipoproteomics: using mass spectrometry-based proteomics to explore the assembly, structure, and function of lipoproteins. J Lipid Res. 50:1967-75.

Amukele TK, Hoofnagle AN, Astion ML. (2009) Use of a resident on-call database to characterize failures in communicating critical laboratory results. Clin Chem. 55:1590-1.

Hoofnagle AN, Becker JO, Wener MH, and Heinecke JW. (2008) Quantification of thyroglobulin, a low-abundance serum protein, by immunoaffinity peptide enrichment and tandem mass spectrometry. Clin Chem. 54:1796-804.

Hoofnagle AN, Peterson GN, Kelly JL, Sayre CA, Chou D, and Hirsch IB. (2008) Use of serum and plasma glucose measurements as a benchmark for improved hospital-wide glycemic control. Endocr Pract. 14:556-63.  
Vaisar T, Pennathur S, Green PS, Gharib SA, Hoofnagle AN, Cheung MC, Byun J, Vuletic S, Kassim S, Singh P, Chea H, Knopp RH, Brunzell J, Geary R, Chait A, Zhao1 X, Elkon K, Marcovina S, Ridker P, Oram JF, and Heinecke JW. (2007) Shotgun Proteomics Implicates Protease Inhibition and Complement Activation in the Anti-inflammatory Properties of HDL. J Clin Invest. 117:746-56.

Hoofnagle AN. (2007) Clinical tumor marker quantification with LC/MS/MS: is there hope? Proceedings of the 23rd Asilomar Conference on Mass Spectrometry, September 1418, 2007. 
Hoofnagle AN and Wener MH. (2006) Serum thyroglobulin: A model of immunoassay imperfection. Clin Lab Int. 12:12-4. 
Hoofnagle AN, Resing KA, and Ahn NG. (2003) Protein Analysis by Hydrogen Exchange Mass Spectrometry. Annu Rev Biophys Biomol Struct. 32:1-25.

Emrick MA, Hoofnagle AN, Miller AS, Ten Eyck LF, and Ahn NG. (2001) Constitutive activation of extracellular signal-regulated kinase 2 by synergistic point mutations. J Biol Chem. 276:46469-79.

Hoofnagle AN, Resing KA, Goldsmith EJ, and Ahn NG. (2001) Changes in protein conformational mobility upon activation of extracellular regulated protein kinase-2 as detected by hydrogen exchange. Proc Natl Acad Sci U S A. 98:956-61.


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