Date & Time
Time: 3:00-4:00 pm (CST), May.14th
Venue: WDR1003
Zoom ID: 937 7164 3410, Passcode: dku
Speaker：
Prof. Kui Ming CHAN
Associate Professor
Department of Biomedical Sciences
City University of Hong Kong
Abstract：
Histones are small nuclear proteins essential for DNA packaging and epigenetic gene regulation. Recent studies on the various cancer associated-histone mutations have revealed the significance of oncohistones in driving different types of cancers. Others and work done by us have previously revealed the identification and characterization of the first oncogenic mutation in genes encode histone H3 (H3K27-to-M in diffuse intrinsic pontine gliomas “DIPG”). The H3K27M mutation occurs in the N-terminal tail domain and affect gene expression via inhibiting PRC2/EZH2 activity and modulating histone post-translational modifications.
In addition to the onco-mutations found in histone H3, we have recently identified three oncogenic mutations in genes encode histone H2B in pancreatic ductal adenocarcinoma “PDAC” and breast cancer. The H2BG53D mutation weakens the interaction between the histone octamer and the nucleosomal DNA. Through analyzing the ATAC-seq, PRO-seq, CUT&RUN and RNA-seq on the CRISPR-Cas9 generated H2BG53D knockin PDAC cells, our data demonstrated that the G53D mutant H2B elevated the transcription of genes involved in cancer properties including cell migration. Depletion of one of the target genes ANXA3 reduced the oncogenic properties in H2BG53D mutant cells, revealing the significance of the H2BG53D mutation in PDAC development. The H2BE76K mutation alters the interaction between Histone H2B and H4, destabilizes the nucleosomes and affects the expression of genes in multiple cancer pathways. I will present our ongoing work of the roles of the above two mutations in pancreatic and breast cancers.
BIO：
Dr K. M. CHAN graduated with BSc and received his PhD at the department of Biochemistry, the University of Hong Kong (HKU). He then moved to Mayo Clinic (Rochester MN, USA) for postdoctoral training and obtained the Edward C. Kendall Research Fellowship in Biochemistry. In February 2015 he joined the Department of Biomedical Sciences (BMS), City University of Hong Kong as a tenure-track Assistant Professor and was promoted to Associate Professor in 2021. Dr Chan is interested in understanding the role of epigenetics in regulating gene expression under physiological and pathological conditions. His group is currently focusing on 1) identifying new cancer driving histone mutations and developing therapeutics for these diseases using different animal models and 2) the role of novel protein factors and RNA binding proteins in X Chromosome inactivation.
