颜光玗
中国医学科学院血液病医院
My research interest lies
in transcription regulation. Our goal is to understand how chromatin regulates
transcription in a spatiotemporal manner and apply this knowledge towards
better diagnosis and management of human diseases. We use the well-known hematopoietic
development as both a technological and conceptual model. To date, we have
identified a two-tipping point model to explain the dynamic progression of how
cell fate transits using in house bioinformatic tools and in vitro
differentiation system. We aim to gain an understanding of the molecular
mechanisms that trigger this phenomenon. The influence of a range of factors,
such as non-canonical nucleosomes and chromatin confirmation, on initiating the
overcoming of tipping point was investigated to ascertain if transcription
bursting and inflammation may potentially contribute to overcoming the first
and second tipping point, respectively. Function is then assessed through
CRISPR/Cas9-engineered depletion of factors, and through biochemical reconstitution
of protein/DNA complexes on a genomic scale. Parallel strategies are being
conducted in model human cell lines and clinical samples. We intend to identify
the contributors that facilitate the tipping point overcoming and their
treatment outcome so as to prevent precancer cells further mature into cancer
cells.