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Transcriptional Mechanism of BRD4 in Solid Tumor

BRD4在实体瘤中的转录机制

基本信息

批准号：
10025103
负责人：
Ming-Ming Zhou
金额：
$ 11.87万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10025103
关键词：
Acetylation Address Affect Amino Acids Antineoplastic Agents BRD2 gene Binding Biochemical Biology Biomedical Research Breast Cancer Cell Bromodomain Cell Cycle Regulation Cell Proliferation Cells Cellular biology Characteristics Chemicals Chemistry Chromatin Complex DNA Repair Data Dependence Disease Drug Targeting Enhancers Epigenetic Process Family Funding Gene Activation Genes Genetic Transcription Genomics Geometry Hematologic Neoplasms Histones Human Human Biology In Vitro Inflammation Inflammatory Investigation Length Lysine Malignant Neoplasms Mediating Mediator of activation protein Mentorship Molecular Nature Oncogenes Oncogenic Plant Roots Positive Transcriptional Elongation Factor B Property Proteins RNA Repression Research Research Personnel Research Project Grants Research Project Summaries Resistance Role Signal Transduction Solid Neoplasm Structure Techniques Testis Therapeutic Time Transcription Coactivator Transcription Elongation Transcriptional Activation acute myeloid leukemia cell base biophysical techniques cancer clinical trial cancer stem cell cancer therapy cell type cohesin combat design drug discovery effective therapy epigenetic regulation gene repression human disease inhibitor/antagonist insight malignant breast neoplasm member neoplastic cell next generation novel novel therapeutic intervention parent grant post-doctoral training recruit small molecule structural biology targeted treatment therapy resistant tool transcription factor triple-negative invasive breast carcinoma tumor

项目摘要

PROJECT SUMMARY The research project planned in this diversity research supplement for Dr. Wilnelly Martinez-Ortiz is constructed based on her research expertise in chemistry, computational structural biology and molecular/cell biology and desire to further her postdoctoral training in chemical biology and small molecule cancer drug discovery for epigenetic proteins. At the same time, this research project that is being developed and refined by Dr. Martinez-Ortiz under the mentorship from Dr. Ming-Ming Zhou is expected to facilitate the Zhou lab’s ongoing efforts in deciphering the fundamental molecular mechanisms that underlie major transcription regulator proteins as they pertain to the epigenetic regulation of gene transcription in biology and human cancers, as described in the parent grant (1R01CA239165-01, PI: MMZ). Specifically, Dr. Wilnelly Martinez-Ortiz will employ the structure-based rational design strategy to develop novel small molecule compounds, which will be used as powerful research tools to study the functional role of BET transcription proteins as key components of the important transcriptional activation complex for gene transcription in chromatin. We expect that this planned research project will help prepare Dr. Wilnelly Martinez-Ortiz to become fully an independent investigator in academic research, who will be capable of identifying most challenging problems in biomedical research, and conceiving and developing scientific approaches to address such problems in human biology and disease.

项目摘要该研究项目计划在这个多样性研究补充博士威尔内利马丁内斯-奥尔蒂斯是基于她在化学，计算结构生物学和分子/细胞生物学，并希望进一步她在化学生物学和小博士后培训分子癌症药物发现表观遗传蛋白。与此同时，这个研究项目，由Martinez-Ortiz博士在周明明博士的指导下开发和完善，预计将促进周实验室正在进行的破译基本分子的努力，主要转录调节蛋白的基础机制，因为它们与表观遗传生物学和人类癌症中基因转录的调节，如父母资助中所述（1R01CA239165-01，PI：MMZ）。具体来说，威尔内利·马丁内斯-奥尔蒂斯博士将采用基于结构的合理的设计策略，开发新的小分子化合物，这将是强大的研究工具，以研究BET转录蛋白的功能作用，作为关键组成部分，染色质中基因转录重要转录激活复合物。我们期望这计划中的研究项目将有助于准备博士威尔内利马丁内斯-奥尔蒂斯成为一个完全独立的研究人员在学术研究，谁将能够确定最具挑战性的问题，生物医学研究，以及构思和发展解决这些问题的科学方法在人类生物学和疾病中。