School of Pharmacy

Edward Kelly

Associate Professor, Department of Pharmaceutics; Assistant Director, Pharmaceutical Bioengineering Extension Program

Department of Pharmaceutics, Pharmaceutics Faculty, UWPKDAP

Telephone: (206) 685-4641

Email: edkelly@uw.edu

Website: Lab website

Education

  • PhD, University of Washington
  • Master of Science and Bachelor of Science, University of California, Riverside

Research Interests

  • Relationship between Bietti’s Crystalline Dystrophy and CYP4V2
  • Differentiation of human pluripotent stem cells into metabolically competent cell types
  • Development of a human “kidney on a chip” for assessment of drug/xenobiotic toxicity

Biography

Dr. Kelly earned his PhD in Biochemistry from the University of Washington in the laboratory of Dr. Richard Palmiter, developing transgenic and knockout mouse models to study the function of the metal-binding protein metallothionein. Following a postdoctoral fellowship in molecular toxicology at the UW Department of Environmental Health with Dave Eaton, he ventured into Biotech, managing the Preclinical Bioanalytics group at Targeted Genetics Corporation, evaluating the safety and efficacy of gene therapies for diseases such as cystic fibrosis, rheumatoid arthritis and hemophilias.

Upon his return to academia, his research interests have stayed within the realm of preclinical biology. His lab works on developing novel models to study normal human physiology and disease states, with a particular focus on cytochrome P450 enzymes and their role in endobiotic/xenobiotic metabolism.

The focus of his lab is on ex vivo modeling of human organ physiology and toxicological responses to drug/xenobiotic challenge.  This research makes use of “organs on chips” or microphysiological systems (MPS) populated with primary and stem-cell derived cell types to recapitulate two key ADME organs, the liver and kidney.  Recent work is extending MPS technologies to model human diseases, as well as how organs respond to the extreme environment of microgravity on the International Space Station.  Dr. Kelly holds the position of Associate Professor in the Department of Pharmaceutics, Adjunct Associate Professor in the Department of Environmental and Occupational Health Sciences and also serves as Co-Director of the Pharmaceutical Bioengineering Program.

PubMed Link

Recent Publications

Kelly, EJ, Wang, Z, Voellinger, JL, Yeung, CK, Shen, DD, Thummel, KE, Zheng, Y, Ligresti, G, Eaton, DL, Muczynski, KA, Duffield, JS, Neumann, T, Tourovskaia, A, Fauver, M, Kramer, G, Asp, E & Himmelfarb, J. Innovations in Preclinical Biology: Engineering of a human kidney tissue microperfusion system. Stem Cell Research and Therapy. 4 Suppl 1:S17. 2013. PMID: 24564863.

Nakano, M, Lockhart, CM, Kelly, EJ & Rettie, AE. Ocular cytochrome P450s and transporters: roles in disease and endobiotic and xenobiotic disposition. Drug Metabolism Reviews. 46(3):247-260. 2014. PMID: 24856391.

Lockhart, CM, Nakano, M, Rettie, AE & Kelly, EJ. Generation and characterization of a murine model of Bietti Crystalline Dystrophy. Investigative Ophthalmology & Visual Science. 55(9):5572-5581. 2014. PMID: 25118264.

Wiek, C, Schmidt, EM, Röllecke, K, Nakano, M, Kelly, EJ, Kaisers, W, Yarov-Yarovoy, V, Rettie, AE & Hanenberg, H. Identification of amino acid determinants in CYP4B1 for optimal catalytic processing of 4-ipomeanol. Biochemical Journal. 465(1):103-114. 2015. PMID: 25247810.

Shuster, DL, Risler, LJ, Prasad, B, Calamia, JC, Voellinger, JL, Kelly, EJ, Unadkat, JD, Hebert, MF, Shen, DD, Thummel, KE & Mao, Q. Identification of CYP3A7 for glyburide metabolism in human fetal livers. Biochemical Pharmacology. 92(4):690-700. 2014. PMID: 25450675.

Adler, M, Ramm, S, Hafner, M, Muhlich, JL, Gottwald, EM, Weber, E, Jaklic, A, Ajay, AK, Svoboda, D, Auerbach, S, Kelly, EJ, Himmelfarb, J & Vaidya, VS. A quantitative approach to screen for nephrotoxic compounds in vitro. Journal of the American Society of Nephrology. 27(4):1015-1028. 2016. PMID: 26260164.

Voellinger, JL & Kelly, EJ. Pharmacogenetic profiling and metabolic activity of human embryonic stem cell derived hepatocytes: focus on CYP450-mediated oxidation. ADMET and DMPK. 4(2):62-83. 2016.

Weber, EJ, Chapron, A, Chapron, BD, Voellinger, JL, Lidberg, KA, Yeung, CK, Wang, Z, Yamaura, Y, Hailey, DW, Neumann, T, Shen, DD, Thummel, KE, Muczynski, KA, Himmelfarb, J & Kelly, EJ. Development of a microphysiological model of human kidney proximal tubule function. Kidney International. 90(3):627-637. 2016. PMID: 27511113. (Article featured on journal cover)

Chang, SY, Weber, EJ, Van Ness, KP, Eaton, DL & Kelly, EJ. Liver and kidney on chips: Micro-physiological models to understand transporter function. Clinical Pharmacology & Therapeutics. 100(5):464-478. 2016. PMID: 27448090.

Wang, L, Collins, C, Kelly, EJ, Chu, X, Ray, AS, Salphati, L, Xiao, G, Lee, C, Lai, Y, Liao, M, Mathias, A, Evers, R, Humphreys, G, Hop, CE, Kumer, SC & Unadkat, JD. Transporter expression in liver tissue from subjects with alcoholic or hepatitis C cirrhosis quantified by targeted quantitative proteomics. Drug Metabolism and Disposition. 44(11):1752-1758. 2016. PMID: 27543206.

Parkinson, OT, Teitelbaum, AM, Whittington, D, Kelly, EJ & Rettie, AE. Species differences in microsomal oxidation and glucuronidation of 4-Ipomeanol: Relationship to target organ toxicity. Drug Metabolism and Disposition. 44(10):1598-1602. 2016. PMID: 27468999.

Prasad, B, Johnson, K, Billington, S, Lee, C, Chung, GW, Brown, CD, Kelly, EJ, Himmelfarb, J & Unadkat, JD. Abundance of drug transporters in the human kidney cortex as quantified by quantitative targeted proteomics. Drug Metabolism and Disposition. 44(12):1920-1924. 2016. PMID: 27621205.

Vernetti, L, Gough, A, Baetz, N, Blutt, S, Broughman, JR, Brown, JA, Foulke-Abel, J, Hasan, N, In, J, Kelly, E, Kovbasnjuk, O, Repper, J, Senutovitch, N, Stabb, J, Yeung, C, Zachos, NC, Donowitz, M, Estes, M, Himmelfarb, J, Truskey, G, Wikswo, JP & Taylor, DL. Functional coupling of human microphysiology systems: Intestine, liver, kidney proximal tubule, blood-brain barrier and skeletal muscle. Scientific Reports. 7:42296. 2017. PMID: 28176881.

Chang, SY, Voellinger, JL, Van Ness, KP, Chapron, B, Shaffer, RM, Neumann, T, White, CC, Kavanagh, TJ, Kelly, EJ & Eaton, DL. Characterization of rat or human hepatocytes cultured in microphysiological systems (MPS) to identify hepatotoxicity. Toxicology In Vitro. 40:170-183. 2017. PMID: 28089783.

Lockhart, CM, Smith, TB, Yang, P, Naidu, M, Rettie, AE, Nath, A, Weleber, R & Kelly, EJ. Longitudinal characterization of function and structure of Bietti crystalline dystrophy: report on a novel homozygous mutation in CYP4V2. British Journal of Ophthalmology. 102:187-194. 2018. PMID: 28698241.

Weber, EJ, Himmelfarb, J & Kelly, EJ. Concise review: Current and emerging biomarkers of nephrotoxicity. Current Opinion in Toxicology [Epub 2017 Apr, 12]. PMID: 29057384

Van Ness, KP, Chang, S-Y, Weber, EJ, Zumpano, D, Eaton, DL & Kelly, EJ. Microphysiological systems to assess nonclinical toxicity. Current Protocols in Toxicology 73:1-14. 2017. PMID: 28777442

Chang, S-Y, Weber, EJ, Sidorenko, VS, Chapron, A, Yeung, CK, Gao, C, Mao, Q, Shen, DD, Wang, J, Rosenquist, TA, Dickman, KG, Neumann, T, Grollman, AP, Kelly, EJ,  Himmelfarb, J & Eaton, DL. Human liver-kidney model elucidates the mechanisms of aristolochic acid nephrotoxicity.  Journal of Clinical Investigation-Insight [Epub 2017 Nov, 16]. PMID: 29202460

Chapron, BD, Chapron, A, Phillips, B, Okoli, MC, Shen, DD, Kelly, EJ, Himmelfarb, J & Thummel KE. Reevaluating the role of megalin in renal vitamin D homeostasis using a human cell-derived microphysiological system. ALTEX 35(4):504-515. 2018. PMID: 2999916

Bajaj, P, Chowdhury, SK, Yucha, R, Kelly, EJ & Xiao, G. Emerging Kidney Models to Investigate Metabolism, Transport, and Toxicity of Drugs and Xenobiotics. Drug Metabolism and Disposition. 46(11):1692-1702. 2018. PMID: 30076203

Sakolish, C, Weber, EJ, Kelly, EJ, Himmelfarb, J, Mouneimne, R, Grimm, FA, House, JS, Wade, T, Han, A, Chiu, WA & Rusyn I. Technology Transfer of the Microphysiological Systems: A Case Study of the Human Proximal Tubule Tissue Chip. Scientific Reports. 8(1):14882. 2018. PMID: 30291268

Monteiro, MB, Ramm, S, Chandrasekaran, V, Boswell, SA, Weber, EJ, Lidberg, KA, Kelly, EJ & Vaidya, VS. A High-Throughput Screen Identifies DYRK1A inhibitor ID-8 that Stimulates Human Kidney Tubular Epithelial Cell Proliferation. Journal of the American Society of Nephrology. [Epub 2018 Oct, 25]. PMID: 30361326.

Rayner, SG, Phong, KT, Xue, J, Lih, D, Shankland, SJ, Kelly, EJ, Himmelfarb, & Zheng, Y. Reconstructing the Human Renal Vascular-Tubular Unit In Vitro. Advanced Healthcare Materials. [Epub 2018 Oct, 31]. PMID: 30379416.

Weber, EJ, Lidberg, KA, Wang, L, Bammler, TK, MacDonald, JW, Li, MJ, Redhair, M, Atkins, WM, Tran, C, Hines, KM, Herron, J, Xu, L, Monteiro, MB, Ramm, S, Vaidya, V, Vaara, M, Vaara, T, Himmelfarb, J & Kelly EJ. Human kidney on a chip assessment of polymyxin antibiotic nephrotoxicity. Journal of Clinical Investigation-Insight. 3(24). PMID: 30568031.

Maass, C, Sorensen, NB, Himmelfarb, J, Kelly, EJ, Stokes, CL & Cirit, M. Translational Assessment of Drug-Induced Proximal Tubule Injury Using a Kidney Microphysiological System. CPT Pharmacometrics Systems Pharmacology. 2019 Mar 14. [Epub ahead of print]. PMID: 30869201.