Professor, Departments of Biopharmaceutical Sciences and Pharmacuetical Chemistry, UCSF
Research Summary
The focus of my laboratory is to understand the genetic basis of drug response and toxicity. Relevant to the Cancer Center are our efforts related to taxane-induced sensory peripheral neuropathy. I was trained as a clinical and molecular pharmacologist and have been involved in pharmacogenetics research for many years. I was an investigator on the Pharmacogenetics of Membrane Transporters project, part of the NIH-sponsored Pharmacogenetics Research Network (PGRN), from 2000-2015, focusing largely on pharmacogenomics of multidrug resistance transporters. Our current focus is on taxane-induced peripheral neuropathy. We use state-of-the-art genomic approaches, such as genome-wide genotyping and next-generation sequencing, to identify genetic biomarkers of drug toxicity and response. Clinical samples largely come from studies within the CALGB/Alliance clinical trial group. Functional genomic studies use cellular systems and model organisms to functionally characterize genetic variants of interest. Collaborative efforts are also ongoing to understand the molecular basis of variability in response to HDAC inhibitors.
Education
Ohio State University, Columbus, OH, B.S., 1985, Pharmacy
University of Washington, Seattle, WA, Ph.D., 1990, Pharmaceutics
National Cancer Institute, Bethesda, MD, 1990-1993, Drug Metabolism
Professional Experience
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1990-1991
Intramural Research Training Award (IRTA) Fellow, Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD
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1991-1993
Pharmacology Research Associate (PRAT) Fellow, Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD
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1993-2000
Assistant Professor of Biopharmaceutical Sciences and Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco, San Francisco, CA
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1995-present
UCSF Liver Center Member
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2000-2006
Associate Professor of Biopharmaceutical Sciences and Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco, San Francisco, CA
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2000-present
Institute for Human Genetics (formerly Program in Human Genetics) Member
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2003-present
Vice Chair for Pharmacogenomics, Department of Biopharmaceutical Sciences, School of Pharmacy, University of California San Francisco, San Francisco, CA
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2006-present
Professor of Biopharmaceutical Sciences and Pharmaceutical Chemistry (now the Department of Bioengineering and Therapeutic Sciences), School of Pharmacy, University of California San Francisco, San Francisco, CA
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2009-present
UCSF Helen Diller Family Comprehensive Cancer Center Member
Honors & Awards
- 1985
Eli Lilly Co. Achievement Award - 1985
Ohio State University Presidential Scholar - 1990
Intramural Research Training Award Fellowship - 1991-1993
Pharmacology Research Associate Fellowship - 1995
Josephine Sitterle Failer Alumni Award, Ohio State University College of Pharmacy - 1996
American Association of Pharmaceutical Sciences New Investigator Award in Pharmacokinetics, Pharmacodynamics and Drug Metabolism - 2002
American Society for Clinical Pharmacology and Therapeutics Leon Goldberg Young Investigator Award - 2008
Elected Fellow, American Association of Pharmaceutical Scientists
Selected Publications
- Eclov RJ, Kim MJ, Smith RP, Liang X, Ahituv N, Kroetz DL. In Vivo Hepatic Enhancer Elements in the Human ABCG2 Locus. Drug Metab Dispos. 2016 Nov 17.
View on PubMed - Li M, Seiser EL, Baldwin RM, Ramirez J, Ratain MJ, Innocenti F, Kroetz DL. ABC transporter polymorphisms are associated with irinotecan pharmacokinetics and neutropenia. Pharmacogenomics J. 2016 Nov 15.
View on PubMed - Yee SW, Giacomini MM, Hsueh CH, Weitz D, Liang X, Goswami S, Kinchen JM, Coelho A, Zur AA, Mertsch K, Brian W, Kroetz DL, Giacomini KM. Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1. Clin Pharmacol Ther. 2016 Jul 22.
View on PubMed - Lee SA, Mefford JA, Huang Y, Witte JS, Martin JN, Haas DW, Mclaren PJ, Mushiroda T, Kubo M, Byakwaga H, Hunt PW, Kroetz DL. Host genetic predictors of the kynurenine pathway of tryptophan catabolism among treated HIV-infected Ugandans. AIDS. 2016 Jul 17; 30(11):1807-15.
View on PubMed - Hertz DL, Owzar K, Lessans S, Wing C, Jiang C, Kelly WK, Patel J, Halabi S, Furukawa Y, Wheeler HE, Sibley AB, Lassiter C, Weisman L, Watson D, Krens SD, Mulkey F, Renn CL, Small EJ, Febbo PG, Shterev I, Kroetz DL, Friedman PN, Mahoney JF, Carducci MA, Kelley MJ, Nakamura Y, Kubo M, Dorsey SG, Dolan ME, Morris MJ, Ratain MJ, McLeod HL. Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14 Polymorphism that Increases Risk of Docetaxel-Induced Neuropathy. Clin Cancer Res. 2016 Oct 1; 22(19):4890-4900.
View on PubMed - Chhibber A, French CE, Yee SW, Gamazon ER, Theusch E, Qin X, Webb A, Papp AC, Wang A, Simmons CQ, Konkashbaev A, Chaudhry AS, Mitchel K, Stryke D, Ferrin TE, Weiss ST, Kroetz DL, Sadee W, Nickerson DA, Krauss RM, George AL, Schuetz EG, Medina MW, Cox NJ, Scherer SE, Giacomini KM, Brenner SE. Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines. Pharmacogenomics J. 2016 Feb 9.
View on PubMed - Yuan B, Yoshino Y, Fukushima H, Markova S, Takagi N, Toyoda H, Kroetz DL. Multidrug resistance-associated protein 4 is a determinant of arsenite resistance. Oncol Rep. 2016 Jan; 35(1):147-54.
View on PubMed - Komatsu M, Wheeler HE, Chung S, Low SK, Wing C, Delaney SM, Gorsic LK, Takahashi A, Kubo M, Kroetz DL, Zhang W, Nakamura Y, Dolan ME. Pharmacoethnicity in Paclitaxel-Induced Sensory Peripheral Neuropathy. Clin Cancer Res. 2015 Oct 1; 21(19):4337-46.
View on PubMed - Barbarino JM, Kroetz DL, Klein TE, Altman RB. PharmGKB summary: very important pharmacogene information for human leukocyte antigen B. Pharmacogenet Genomics. 2015 Apr; 25(4):205-21.
View on PubMed - Haenisch S, Zhao Y, Chhibber A, Kaiboriboon K, Do LV, Vogelgesang S, Barbaro NM, Alldredge BK, Lowenstein DH, Cascorbi I, Kroetz DL. SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients. Neurobiol Dis. 2015 May; 77:127-40.
View on PubMed - Chhibber A, Kroetz DL, Tantisira KG, McGeachie M, Cheng C, Plenge R, Stahl E, Sadee W, Ritchie MD, Pendergrass SA. Genomic architecture of pharmacological efficacy and adverse events. Pharmacogenomics. 2014 Dec; 15(16):2025-48.
View on PubMed - Barbarino JM, Kroetz DL, Altman RB, Klein TE. PharmGKB summary: abacavir pathway. Pharmacogenet Genomics. 2014 May; 24(5):276-82.
View on PubMed - Martin MA, Hoffman JM, Freimuth RR, Klein TE, Dong BJ, Pirmohamed M, Hicks JK, Wilkinson MR, Haas DW, Kroetz DL. Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing: 2014 update. Clin Pharmacol Ther. 2014 May; 95(5):499-500.
View on PubMed - Chhibber A, Mefford J, Stahl EA, Pendergrass SA, Baldwin RM, Owzar K, Li M, Winer EP, Hudis CA, Zembutsu H, Kubo M, Nakamura Y, McLeod HL, Ratain MJ, Shulman LN, Ritchie MD, Plenge RM, Witte JS, Kroetz DL. Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance). Pharmacogenomics J. 2014 Aug; 14(4):336-42.
View on PubMed - Nicol MR, Fedoriw Y, Mathews M, Prince HM, Patterson KB, Geller E, Mollan K, Mathews S, Kroetz DL, Kashuba AD. Expression of six drug transporters in vaginal, cervical, and colorectal tissues: Implications for drug disposition in HIV prevention. J Clin Pharmacol. 2014 May; 54(5):574-83.
View on PubMed - Markova SM, Schwartz JB, Kroetz DL. Response to "CYP2C9 polymorphism is not a major determinant of bosentan exposure in healthy volunteers". Clin Pharmacol Ther. 2014 Mar; 95(3):252.
View on PubMed - Micheli JE, Chinn LW, Shugarts SB, Patel A, Martin JN, Bangsberg DR, Kroetz DL. Measuring the overall genetic component of nevirapine pharmacokinetics and the role of selected polymorphisms: towards addressing the missing heritability in pharmacogenetic phenotypes? Pharmacogenet Genomics. 2013 Nov; 23(11):591-6.
View on PubMed - Markova SM, Kroetz DL. ABCC4 is regulated by microRNA-124a and microRNA-506. Biochem Pharmacol. 2014 Feb 1; 87(3):515-22.
View on PubMed - Liu Y, Lu X, Nguyen S, Olson JL, Webb HK, Kroetz DL. Epoxyeicosatrienoic acids prevent cisplatin-induced renal apoptosis through a p38 mitogen-activated protein kinase-regulated mitochondrial pathway. Mol Pharmacol. 2013 Dec; 84(6):925-34.
View on PubMed - Motsinger-Reif AA, Jorgenson E, Relling MV, Kroetz DL, Weinshilboum R, Cox NJ, Roden DM. Genome-wide association studies in pharmacogenomics: successes and lessons. Pharmacogenet Genomics. 2013 Aug; 23(8):383-94.
View on PubMed
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