Edward Kelly

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

Department of Pharmaceutics, Pharmaceutics Faculty, UWPKDAP

Expertise: Biotechnology, Pharmacogenomics and Personalized Medicine, Toxicology

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.

Active areas of research in the Kelly lab include studies on the function of the “orphan” P450 CYP4V2 in the heritable eye disease Bietti’s Crystalline Dystrophy and ex vivo modeling of human organ physiology and toxicological responses to drug/xenobiotic challenge.  This latter project 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 select 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 Extension Program.

PubMed Link

Perez HD, Kelly E, Chenoweth D & Elfman F. Identification of the C5a des-Arg cochemotaxin. Homology with vitamin D-binding protein (Gc globulin). Journal of Clinical Investigation 82: 360-363, 1988.

Perez HD, Kelly E & Elfman F. Identification of the C5a des-Arg cochemotaxin. Transactions of the Association of American Physicians 101: 242-249, 1988.

Lobo E, Elfman F, Kelly E & Perez HD. Effect of phorbol myristate acetate on processing of formyl peptide receptors by human neutrophils. Biochimica et Biophysica Acta 1055: 193-196, 1990.

Perez HD, Kelly E, Elfman F, Armitage G & Winkler J. Defective polymorphonuclear leukocyte formyl peptide receptor(s) in juvenile periodontitis. Journal of Clinical Investigation 87: 971-976, 1991.

Perez HD, Kelly E & Holmes R. Regulation of formyl peptide receptor expression and its mRNA levels during differentiation of HL-60 cells. Journal of Biological Chemistry 267: 358-363, 1992.

Perez HD, Holmes R, Kelly E, McClary J & Andrews WH. Cloning of a cDNA encoding a receptor related to the formyl peptide receptor of human neutrophils. Gene 118: 303-304, 1992.

Perez HD, Holmes R, Kelly E, McClary J, Chou Q & Andrews WH. Cloning of the gene coding for a human receptor for formyl peptides. Characterization of a promoter region and evidence for polymorphic expression. Biochemistry 31: 11595-11599, 1992.

Masters BA, Kelly EJ, Quaife CJ, Brinster RL & Palmiter RD. Targeted disruption of metallothionein I and II genes increases sensitivity to cadmium. Proceedings of the National Academy of Sciences USA 91: 584-588, 1994.

Quaife CJ, Findley SD, Erickson JC, Froelick GJ, Kelly EJ, Zambrowicz BP & Palmiter RD. Induction of a new metallothionein isoform (MT-IV) occurs during differentiation of stratified squamous epithelia. Biochemistry 33: 7250-7259, 1994.

Masters BA, Quaife CJ, Erickson JC, Kelly EJ, Froelick GJ, Zambrowicz BP, Brinster RL & Palmiter RD. Metallothionein III is expressed in neurons that sequester zinc in synaptic vesicles. Journal of Neuroscience 14: 5844-5857, 1994.

Erickson JC, Masters BA, Kelly EJ, Brinster RL & Palmiter RD. Expression of human metallothionein-III in transgenic mice. Neurochemistry International 27: 35-41, 1995.

Kelly EJ, Quaife CJ, Froelick GJ & Palmiter RD. Metallothionein-I and -II protect mice against zinc deficiency and zinc toxicity. Journal of Nutrition 126: 1782-1793, 1996.

Kelly EJ & Palmiter RD. A murine model of Menkes disease reveals a physiological function of metallothionein. Nature Genetics 13: 219-222, 1996.

Kelly EJ & Palmiter RD. A pair of adjacent glucocorticoid response elements regulate expression of two mouse metallothionein genes. Proceedings of the National Academy of Sciences USA 94: 10045-10050, 1997.

Quaife CJ, Kelly EJ, Masters BM, Brinste, RL & Palmite, RD. Ectopic expression of metallothionein-III causes pancreatic acinar cell necrosis in transgenic mice. Toxicology and Applied Pharmacology 148: 148-157, 1998.

Payne AS, Kelly EJ & Gitlin JD. Functional expression of the Wilson disease protein reveals mislocalization and impaired copper-dependent trafficking of the common H1069Q mutation. Proceedings of the National Academy of Sciences USA 95:10854-10859, 1998.

Tonge RP, Kelly EJ, Bruschi SA, Kalhorn T, Eaton DL, Nebert DW & Nelson SD. Role of CYP1A2 in the hepatotoxicity of acetaminophen: investigations using Cyp1a2 null mice. Toxicology and Applied Pharmacology 153: 102-108, 1998.

Wang C, Bammler TK, Guo Y, Kelly EJ & Eaton DL. Mu-class GSTs are responsible for aflatoxin B(1)-8,9-epoxide-conjugating activity in the nonhuman primate Macaca fascicularis liver. Toxicological Sciences 56: 26-36, 2000.

Cheesman MJ, Kneller MB, Kelly EJ, Thompson SJ, Yeung CK, Eaton DL & Rettie AE. Purification and characterization of hexahistidine-tagged cyclohexanone monooxygenase expressed in Saccharomyces cerevisiae and Escherichia coli. Protein Expression and Purification 21: 81-86, 2001.

Eaton DL, Bammler TK & Kelly EJ. Interindividual differences in response to chemoprotection against aflatoxin-induced hepatocarcinogenesis: implications for human biotransformation enzyme polymorphisms. Advances in Experimental Medicine and Biology 500:559-576, 2001.

Kelly EJ, Erickson KE, Sengstag C & Eaton DL. Expression of human microsomal epoxide hydrolase in Saccharomyces cerevisiae reveals a functional role in aflatoxin B1 detoxification. Toxicological Sciences 65: 35-42, 2002.

McConnachie LA, Bodor M, Philips B., Kelly EJ, Shen DD & Ho RJY. An RT-PCR-based strategy to estimate full-length CYP2D6 mRNA copy number. Genetic Testing 8: 313-318, 2004.

Bodor M, Kelly EJ, & Ho RJY. Characterization of the Human MDR1 Gene. American Association of Pharmaceutical Scientists Journal 7: E1-E5, 2005.

Salama NN, Kelly EJ, Bui T & Ho RJY. The impact of pharmacologic and genetic knockout of P-glycoprotein on nelfinavir levels in the brain and other tissues in mice. Journal Pharmaceutical Sciences 94: 1216-1225. 2005.

Redman AR, Zheng J, Shamsi SA, Kelly EJ, Ho RJY. Ritchie DM, & Hon YY, 2008. Variant CYP2C9 Alleles and Warfarin concentrations in Patients Receiving low vs. Average Dose Warfarin Therapy. Clin Appl Thromb Hemost. 14(1):29-37.

Rettie AR & Kelly EJ. The CYP4 family, In: Cytochrome P450: Role in the Metabolism and Toxicity of Drugs and Other Xenobiotics, C Ioannides ed., Royal Society of Chemistry Publishing.

Hebert MF, Ma X, Naraharisetti SB, Krudys KM, Umans JG, Hankins GD, Caritis SN, Miodovnik M, Mattison DR, Unadkat JD, Kelly EJ, Blough D, Cobelli C, Ahmend MS, Snodgrass WR, Carr DB, Easterling TR, Vicini P. Are we optimizing gestational diabetes with glyburide? The pharmacological basis for better clinical practice. Clinical Pharmacology & Therapeutics 85(6): 607-614. 2009

Nakano M, Kelly EJ & Rettie AE. Expression and characterization of CYP4V2 as a fatty acid _ hydroxylase. Drug Metabolism and Disposition 37(11): 2119-2122. 2009. Epub 2009 Aug 6.

Eyal S, Easterling TR, Carr D, Umans JG, Miodovnik M, Hankins GD, Clark SM, Risler L, Wang J, Kelly EJ, Shen DD, Hebert MF. Pharmacokinetics of metformin during pregnancy. Drug Metabolism and Disposition 38(5): 833-840. 2010. Epub 2010 Jan 29.

Abassi N, Vadnais B, Knutson JA, Blough DK, Kelly EJ, O’Donnell PV, Deeg HJ, Pawlikowski MA, Ho RJ & McCune JS. Pharmacogenetics of intravenous and oral busulfan in hematopoietic cell transplant recipients. Journal of Clinical Pharmacology. 2010 Dec 8. [Epub ahead of print]

Kelly EJ, Nakano M, Rohatgi P, Yarov-Yarovoy V & Rettie AE. CYP4V2 and CYP4F22: Orphan P450s for orphan ocular and skin diseases. Molecular Interventions, in press (2011).

Crouthamel MH, Kelly EJ & Ho RJY. Development and characterization of transgenic mouse models for conditional gene knockout in the blood-brain and blood-CSF barriers. Transgenic Research (accepted for publication).

Ho MT, Kelly EJ, Bodor M, Buit T, Kowdley KV & Ho RJ. Novel cytochrome P450-2D6 promoter sequence variations in hepatitis C positive and negative subjects. Annals of Hepatology. 10(3):327-332. 2011.

Parkinson OT, Kelly EJ & Ho RJY. Development and characterization of transgenic mouse models for conditional gene knockout in the blood-brain and blood-CSF barriers. Transgenic Research. 21(1):113-130. 2012.

Takakusa H, Mohar I, Kavanagh TJ, Kelly EJ, Kaspera R & Nelson SD. Protein tyrosine nitration of mitochondrial carbamoyl phosphate synthetase 1 and its functional consequences. Biochemical and Biophysical Research Communications. 420(1):54-60. 2012.

Okialda KA, Stover NB, Weleber RG & Kelly EJ. Bietti Crystalline Dystrophy. In: Pagon, RA, Bird, TD, Dolan, CR, Stephens, K, Adam, MP, editors. GeneReviews Seattle (WA): University of Washington, Seattle; 1993-. 2012.

Kelly EJ, Yarov-Yarovoy V & Rettie AE. CYP4B1 (cytochrome P450, family 4, subfamily B, polypeptide 1). Atlas of Genetics and Cytogenetics in Oncology and Haematology. May 2012. http://AtlasGeneticsOncology.org/Genes/CYP4B1ID40253ch1p33.html

Nakano M, Kelly EJ, Wiek C, Hanenberg H & Rettie AE. CYP4V2 in Bietti’s Crystalline Dystrophy: Ocular localization, metabolism of _-3 polyunsaturated fatty acids and functional deficit of the p.H331P variant. Molecular Pharmacology. 82(4):679-686. 2012.

Topletz A, Le HN, Lee N, Kelly EJ, Wang J & Isoherranen N. Hepatic Cyp2d and Cyp26a1 mRNAs and activities are increased during mouse pregnancy. Drug Metabolism and Disposition. 41(2):312-319. 2013.

Parkinson OT, Liggitt HD, Rettie AE & Kelly EJ. Generation and Characterization of a Cyp4b1 null mouse and the role of CYP4B1 in the activation and toxicity of ipomeanol. Toxicological Sciences. 134(2):243-250. 2013. PMID: 23748241.

Lee, N, Hebert, MF, Prasad, B, Easterling, TR, Kelly, EJ, Unadkat, JD & Wang, J. Effect of gestational age on mRNA and protein expression of polyspecific organic cation transporters during pregnancy. Drug Metabolism and Disposition. 41(12):2225-2232. 2013. PMID: 24101703.

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. Dec.20.; 4 Suppl. [Epub ahead of print]. 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. 2014 May 26 [Epub ahead of print]. 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. 2014 Aug 12 [Epub ahead of print]. PMID: 25118264.

Wiek, C, Schmidt, EM, Rí_llecke, 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. 2014 Sep 23 [Epub ahead of print]. PMID: 25247810.