BRCA1 AND X CHROMOSOME INACTIVATION

候选人：Shridar Ganesan的职业目标是成为一名独立的癌症研究人员，专注于乳腺癌生物学，对BRCA1肿瘤抑制基因及其参与染色质结构的调节有特殊的兴趣。这项关于乳腺癌发展机制的基础研究将通过他参与乳腺癌患者的临床护理来补充。Howard Temin奖将帮助他过渡到一个完全独立的位置，作为科学研究者和教员。在接下来的几年里，大卫·利文斯顿博士对他的指导将是提高他的研究技能和在BRCA1生物学领域建立存在的关键，从而使他能够顺利过渡到独立的研究职位。

DESCRIPTION (provided by applicant): Candidate: Shridar Ganesan's career goal is to become an independent cancer researcher focused on the biology of breast cancer with a specific interest in the BRCA1 tumor suppressor gene and its involvement in the regulation of chromatin structure. This basic research in the mechanism of breast cancer development will be complemented by his clinical involvement in the care of breast cancer patients. The Howard Temin Award will assist his transition to a fully independent position as scientific investigator and faculty member. His mentorship by Dr. David Livinston over the next several years will be critical for refining his research skills and establishing a presence in the field of BRCA1 biology, and thus, allow a smooth transition to an independent research position. Environment: The Dana-Farber Cancer Institute and Harvard Medical School provide an excellent environment with the resources and collaborative opportunities required for the completion of the research goals outline in this proposal. His mentor Dr. Livingston has an outstanding record as an excellent mentor and his laboratory provides a stimulating, supportive, and productive intellectual and scientific environment. Research: The hypothesis and specific aims are: Hypothesis: BRCA1 interacts with XlST RNA and is required for proper maintenance of chromatin structure necessary for silencing of the inactive X chromosome. BRCA1 may interact similarly with other RNA species to participate in regulation of chromatin structure elsewhere in the genome. Specific Aims: 1. Identify and characterize the regions of interaction between BRCA1 and XIST RNA. 2. Determine the effects of BRCA1 loss on the state of histone methylation of the inactive X chromosome. 3. Determine if BRCA1 interacts with other RNA species besides XIST RNA.