Clinical Relevance of Cytochrome P450 Pharmacogenetics

描述（由申请人提供）：本申请介绍了一项以患者为导向的研究计划，旨在支持大卫弗洛克哈特医学博士，博士进行的指导和研究计划。申请人是一名GCRC研究者，在其指定的研究领域（临床药物遗传学）中，在资助和出版的、以患者为导向的研究和指导方面拥有大量记录。他的职业生涯已经达到了一个快速而富有成效的增长阶段，在这个阶段，繁重的临床和行政责任可能会削弱他的生产力。该奖项将使他能够继续专注于细胞色素P450药物遗传学领域以患者为导向的研究，并指导初级临床研究人员。候选人将继续并扩大细胞色素P450药物遗传学广泛领域的多学科研究计划，重点关注已知具有明确功能多态性的两种酶：CYP2D6和CYP3A5，以及需要更多研究的酶：CYP2B6。指导机会将来自正在进行的乳腺癌治疗药物遗传学研究，包括旨在验证细胞色素P450药物遗传学可用于预测他莫昔芬效果的假设的研究，以及来自芳香化酶抑制剂，艾滋病毒，镰状细胞病和儿科肿瘤学领域的研究，申请人在其中发挥积极的指导作用。Flockhart博士是印第安纳州大学临床药理学系主任。T-32临床药理学培训补助金和药物基因组学，伦理学和公共政策研究金的共同主任。因此，他非常有资格在临床药物基因组学领域提供临床研究培训，并指导年轻的临床研究者。医学的印第安纳州大学学院是一个优秀的环境，以病人为导向的研究与强大的GCRC，强大的信息学基础设施和一个充满活力的中心生物伦理学，所有这些都是承诺，为候选人的机构支持。

DESCRIPTION (provided by applicant): 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 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.