Alcohol Dependence: Pharmacotherapy, Pharmacogenetics, and Genetics

描述（由申请人提供）：鉴于对酒精使用障碍（AUD）的新的和更有效的治疗方法的需求不断增长，这在人群中非常普遍，需要具有酒精治疗研究专业知识的研究者。还需要熟悉人类遗传学，特别是药物遗传学的研究人员将这些快速发展的领域转化为治疗AUD患者的有意义的进展。我提出了一个为期四年的计划，在亨利克兰兹勒博士的监督和指导下，在康涅狄格大学健康中心的NIAAA资助的酒精研究中心进行以病人为导向的指导研究（POR）。该计划包括完成应用统计方面的大量课程和辅导，重点是将药物遗传学应用于对酒精的急性反应和酒精依赖的治疗。我还将完成翻译基因组学的课程，以帮助我实现我的主要目标，即在四年职业奖励期结束时，开发一个独立的药物遗传学应用于酒精依赖临床试验的研究项目。我将在40名酒精依赖受试者中完成一项为期12周的新型抗惊厥药唑尼沙胺的随机、安慰剂对照临床试验，这将为我提供更多研究提案的试点数据。我也将继续我的工作，在正在进行的试验和人类酒精挑战研究，所有这些都包括药物遗传学的组成部分。新技能的获得将通过正式的课程（包括研究的道德行为）和与既定研究者的持续合作以及在临床试验和药物遗传学方面的持续指导（使我能够在正在进行的临床研究的背景下应用在课堂上学到的技能）来实现。我也将继续发展我的技能，在grananitary，手稿准备，有效的沟通，学术合作和领导。这个修订后的应用程序包含大量的修改，导致重点突出的职业发展和研究计划，并解释了进一步培训的必要性。获得这个奖项是我作为临床酒精研究人员继续发展的关键。

DESCRIPTION (provided by applicant): In view of the growing demand for new and more effective treatments for alcohol use disorders (AUDs), which are highly prevalent in the population, a need exists for investigators with expertise in the conduct of alcohol treatment research.. There is also a need for researchers who are conversant with human genetics and in particular, pharmacogenetics, to translate these rapidly evolving fields into meaningful advances in the treatment of patients with AUDs. I propose a four-year plan of mentored patient-oriented research (POR) at the the NIAAA-funded Alcohol Research Center at the Univ. of CT Health Center under the supervision and mentorship of Dr. Henry Kranzler. The plan includes completion of substantial coursework and mentoring in applied statistics, with an emphasis on the application of pharmacogenetics to both the acute response to alcohol and the treatment of alcohol dependence. I will also complete coursework in translational genomics to assist me in achieving my main goal of developing an independent program of research on the application of pharmacogenetics to clinical trials for alcohol dependence by the end of the four-year career award period. I will complete a 12-week randomized, placebo-controlled clinical trial of the novel anticonvulsant zonisamide in 40 alcohol dependent subjects, which will provide me with pilot data for additional research proposals. I will also continue my work in ongoing trials and human alcohol challenge studies, all of which include pharmacogenetic components. The acquisition of new skills will be achieved through formal coursework (including the ethical conduct of research) and continued collaboration with established investigators and the ongoing receipt of mentoring in clinical trials and pharmacogenetics (to enable me to apply the skills learned in the classroom in the context of ongoing clinical research). I will also continue to develop my skills in grantsmanship, manuscript preparation, effective communication, academic collaboration, and leadership. This revised application contains substantial revisions resulting in well-focused career development and research plans, and explication of the need for further training. Receipt of this award is key to my continued development as a clinical alcohol researcher.