Molecular Mechanisms of Liver Fibrosis (Diversity Supplement)

项目总结/摘要 NIAAA R37补助金的多样性补充是为了支持候选人Amani Lee博士。 博士Amani Lee将抑制表观遗传调节剂的流动性和基质 肝星状细胞（HSC）的形成。他将使用两种商业抑制剂（例如， Tazemetostat，iBET151）和新型抑制剂，由密歇根大学的合作者开发， 明尼苏达州，阐明将影响活化/迁移和基质的下游效应 形成HSC。假设共抑制减少了HSC的迁移， 肝脏疾病模型中的纤维化。总的来说，这种方法有可能识别出 下游目标，融合两个调控途径，以及，突出的潜力， 酒精相关性肝纤维化的药物联合治疗。本补充将联合收割机 博士Lee在化学方面的专业知识与他学习如何翻译前沿生物医学的愿望 研究有效和实际的临床应用。鉴于他的博士学位，他将独立地 在基于实验室的实验中发挥作用，并制定必要的方法， 项目他还将在实验室接受先进分子遗传学和细胞生物学技术的培训 沙阿实验室的成员此外，他将有机会审计研讨会和短期 课程，以提高他的分子生物学和表观遗传学的背景知识。博士 沙阿将每周与李博士一对一的会议，除了季度会议，其中 他们将审查李博士的职业发展计划。此外，李博士将在 如何查找、起草和提交基金申请、临床期刊论文和会议 出版物。我们的目标是在批准后的24个月内，李博士将非常适合申请 对于NIH资助（例如，F32），以及，获得工具来设计自己的生物实验 受酒精相关性肝病影响的系统

Project Summary/Abstract This diversity supplement to the NIAAA R37 grant is in support of the candidate Dr. Amani Lee. Dr. Amani Lee will pharmacologically inhibit epigenetic regulators of the mobility and matrix formation of hepatic stellate cells (HSCs). He will work with both commercial inhibitors (e.g. Tazemetostat, iBET151) and novel inhibitors, developed by collaborators at the University of Minnesota, to elucidate downstream effects that will influence activation/migration and matrix formation for HSCs. Co-inhibition is hypothesized to reduce both the migration of HSCs and fibrogenesis in liver disease models. In total, this approach has the potential to identify downstream targets that converge two regulatory pathways, as well as, highlight the potential for a pharmacological co-treatment of alcohol-associated liver fibrosis. This supplement will combine Dr. Lee’s expertise in chemistry with his desire to learn how to translate frontier biomedical research into effective and practical clinical applications. Given his PhD, he will independently function in bench-based experimentation and develop methodology necessary to advance the project. He will also be trained in advanced molecular genetics and cell biology techniques by lab members in the Shah Lab. Additionally he will have the opportunity to audit workshops and short courses at Mayo to enhance his background knowledge of molecular biology and epigenetics. Dr. Shah will have weekly one-on-one meetings with Dr. Lee, in addition to quarterly meetings, where they will review Dr. Lee’s career development plans. Furthermore, Dr. Lee will be co-mentored in how to find, draft, and submit grant applications, clinical journal papers, and conference publications. It is our goal that within 24 months of approval Dr. Lee will be well-suited to apply for NIH grants (e.g., F32), as well as, obtain the tools to design his own experiments on biological systems affected by alcohol-associated liver disease.