This application presents a program of patient-oriented research designed to support a mentoring and research plan carried out by David Flockhart MD, PhD. The applicant is a GCRC investigator, who has a substantial track record in funded and published, patient-oriented investigation and mentoring in his designated area of study: Clinical Pharmacogenetics. He has reached a stage of rapid and productive growth in his career, at which heavy clinical and administrative responsibilities threaten to undermine his productivity. This award should allow him to continue to focus on patient-oriented research in the area of cytochrome P450 pharmacogenetics and on the mentoring of junior clinical investigators. The candidate will continue and expand a multidisciplinary research program in the broad area of cytochrome P450 pharmacogenetics, focusing on two enzymes known to possess clear functional polymorphisms: CYP2D6 and CYP3A5, and one where more research is necessary: CYP2B6. Mentoring opportunities will derive from ongoing studies on the pharmacogenetics of the treatment of breast cancer, including studies designed to test the hypothesis that cytochrome P450 pharmacogenetics can be used to anticipate the effects of tamoxifen, as well as from studies in the areas of Aromatase inhibitors, HIV, Sickle Cell disease and Pediatric Oncology in which the applicant plays an active mentoring role. Dr. Flockhart is Director of the Division of Clinical Pharmacology at Indiana University, P.I. of a T-32 Clinical Pharmacology Training Grant and co-director of a fellowship in Pharmacogenomics, Ethics and Public Policy. As such, he is highly _ qualified to provide clinical research training in the area of clinical pharmacogenomics, and to mentor young clinical investigators. The Indiana University School of Medicine is an outstanding environment for patient- oriented research with a strong GCRC, a strong informatics infrastructure and a vigorous Center for Bioethics, all of which are committed, institutional supports for the candidate.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
Application #
Study Section
Clinical Oncology Study Section (CONC)
Program Officer
Wilde, David B
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Indiana University-Purdue University at Indianapolis
Internal Medicine/Medicine
Schools of Medicine
United States
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Ingle, James N; Kalari, Krishna R; Buzdar, Aman U et al. (2015) Estrogens and their precursors in postmenopausal women with early breast cancer receiving anastrozole. Steroids 99:32-8
Lu, Wenjie Jessie; Thong, Nancy; Flockhart, David A (2012) Reduced methadone clearance during aromatase inhibition. J Clin Psychopharmacol 32:511-7
Philips, Santosh; Richter, Alexandra; Oesterreich, Steffi et al. (2012) Functional characterization of a genetic polymorphism in the promoter of the ESR2 gene. Horm Cancer 3:37-43
Lu, Wenjie Jessie; Xu, Cong; Pei, Zifan et al. (2012) The tamoxifen metabolite norendoxifen is a potent and selective inhibitor of aromatase (CYP19) and a potential lead compound for novel therapeutic agents. Breast Cancer Res Treat 133:99-109
Lu, Wenjie Jessie; Desta, Zeruesenay; Flockhart, David A (2012) Tamoxifen metabolites as active inhibitors of aromatase in the treatment of breast cancer. Breast Cancer Res Treat 131:473-81
Lu, Wenjie Jessie; Ferlito, Valentina; Xu, Cong et al. (2011) Enantiomers of naringenin as pleiotropic, stereoselective inhibitors of cytochrome P450 isoforms. Chirality 23:891-6
Ramamoorthy, Anuradha; Flockhart, David A; Hosono, Naoya et al. (2010) Differential quantification of CYP2D6 gene copy number by four different quantitative real-time PCR assays. Pharmacogenet Genomics 20:451-4
Ingle, James N; Buzdar, Aman U; Schaid, Daniel J et al. (2010) Variation in anastrozole metabolism and pharmacodynamics in women with early breast cancer. Cancer Res 70:3278-86
Kreutz, Rolf P; Stanek, Eric J; Aubert, Ronald et al. (2010) Impact of proton pump inhibitors on the effectiveness of clopidogrel after coronary stent placement: the clopidogrel Medco outcomes study. Pharmacotherapy 30:787-96
Lu, Wenjie Jessie; Bies, Robert; Kamden, Landry K et al. (2010) Methadone: a substrate and mechanism-based inhibitor of CYP19 (aromatase). Drug Metab Dispos 38:1308-13

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