Molecular Mechanisms of Liver Fibrosis (Diversity Supplement)

项目摘要/摘要 这项对NIAAA R37拨款的多样性补充是为了支持候选人Amani Lee博士。 Amani Lee博士将从药物上抑制流动性和基质的表观遗传调节 肝星状细胞(HSCs)的形成。他将使用这两种商业抑制剂(例如， TazemTostat，iBET151)和新型抑制剂，由德克萨斯大学的合作者开发 以阐明将影响激活/迁移和基质的下游效应 为HSCs编队。共同抑制被认为可以减少HSCs的迁移和 肝病模型中的肝纤维化。总而言之，这种方法有可能确定 下游目标汇聚了两条监管途径，以及突显了 酒精性肝纤维化的药理联合治疗。本副刊将结合 李博士在化学方面的专业知识与他学习如何将前沿生物医学 研究有效和实用的临床应用。鉴于他的博士学位，他将独立 在基于实验台的实验中的作用，并开发必要的方法学来推进 项目。他还将在实验室接受高级分子遗传学和细胞生物学技术方面的培训 沙阿实验室的成员。此外，他还将有机会审核研讨会和短片 在梅奥的课程，以加强他的分子生物学和表观遗传学的背景知识。Dr。 沙阿将与李博士每周举行一对一的会议，此外还将每季度举行一次会议， 他们将审查李博士的职业发展计划。此外，李博士还将在 如何查找、起草和提交拨款申请、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的拨款(例如，F32)，以及获得工具来设计他自己的生物学实验 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.