Hua-Ying Fan, PhD
Cellular and Molecular Oncology
New York University (1996)
Mass General Hospital / Harvard Medical School (2006)
Visit for More Information
Fan Lab - http://cancer.unm.edu/research/programs/cancer-genetics-epigenetics-genomics/fan-lab/
Published Works - http://www.ncbi.nlm.nih.gov/sites/myncbi/hua-ying.fan.1/bibliography/40329768/public/?sort=date&direction=descending
The goal of this proposal is to unravel epigenetic mechanisms; specifically, how transcription factors are selectively bound to mitotic chromatin and their impact on cell identity maintenance. We will use RBPJ, the major downstream effector of the Notch signaling, as a model protein for this proposal. We have recently developed strategies to manipulate RBPJ-mitotic chromatin interactions and these had fruitfully provided a handle for us to elucidate a regulatory mechanism of RBPJ-mitotic chromatin interaction in the mouse embryonal carcinoma cells (Dreval, Lake and Fan, manuscript in revision). This is the first example in our knowledge that one could manipulate the interaction of sequence-specific transcription factors and mitotic chromatin. Equally important, we demonstrate that this altered RBPJ-mitotic chromatin interaction impacts transcription reactivation upon mitotic exit. Together these results support that notion that RBPJ functions as a mitotic bookmarking factor and that may contribute the maintenance of specific transcription programs through cell divisions and thus cell identity. Our preliminary data had led us to propose a model that accounts for selective binding of sequence-specific transcription factors in different cells with different transcription programs. In this grant application, we propose to valid our preliminary results using genome-wide approaches. In addition, we’d like to extend to the human T-ALL, since aberrant Notch activation is found in more than 50% of T-ALL patients. This work will not provide insights into how specific transcription programs may propagated through cell division, it may reveal new therapeutic targets.
We are very excited about our recent breakthrough in the project and we have reagents, expertise and collaborators in place. I have extensive experience in epigenetic regulations, especially on how chromatin structure is regulated by energy-dependent chromatin structure regulators and transcription factors, and how defects in these proteins lead to disease. My research has been funded by NIH since I was a postdoctoral fellow, including K01 and R01s and that had rendered me experience in project management. My laboratory has worked out the protocols to obtain highly purified mitotic cells (both adherent and suspension cells) and to perform chromatin immunoprecipitation followed by deep sequencing (ChIP-seq). Dr. Guo will process all the next-gen data analysis. Dr. Lake has an extensive training in the field of Notch biology during his postdoctoral studies with Dr. S. Artavanis-Tsakonas in Harvard Medical School. In addition, we have two local experts in T-cells biology (Dr. Cannon and Dr. Matlawska-Wasowska) as our consultants. They will assist our endeavor to study mitotic bookmarking by RBPJ in T cells. I believe my expertise in chromatin biology, amble preliminary results and excellent collaborators will ensure the success of completion of this proposal and provide novel insights into the mechanisms underlies mitotic transcriptional memory.