Department: Medical Oncology
Medical School: Tsinghua University School of Life Science, China
Academic Rank: Researcher
Determine to what extent oncohistones promote the formation of tumors
Screen the potential drug targets for tumors harboring oncohistone
Determine how epigenetic information is precisely distributed
Natural Science Award of Ministry of Education, First Prize
Recent genetic studies have identified two somatic oncohistone mutations, H3.3K27M and H3.3K36M, in over 75% DIPG cases and in more than 90% chondroblastoma cases, respectively. With the high incidence of histone H3 lysine to methionine mutations, it is critically important to understand how these methionine substitutions promote tumorigenesis. Dr. Fang's team has shown that oncohistone H3.3K27M reprograms H3K27 methylation and gene expression in DIPG cases, as well as oncohistone H3.3K36M inhibits H3K36 methyltransferases to reprograms the epigenome of chondroblastomas. Dr. Fang will use biochemistry, molecular biology, epigenomic approaches, and large screening to study the function of oncohistone mutations and the molecular mechanisms for the inheritance of epigenetic information.
Sun Z*, Zhang Y*, Jia J, Fang Y, Tang Y, Wu H, Fang D#, H3K36me3, message from chromatin to DNA damage repair, Cell & Bioscience, 2020, 10(9): 2045-3701.
Fang D*, Gan H*, Cheng L, Lee J, Zhou H, Sarkaria J, Daniels D, Zhang Z#. H3.3K27M mutant proteins reprogram epigenome by sequestering the PRC2 complex to poised enhancers. eLife, 2018, 7:e36696.
Fang D, Gan H, Wang H, Zhou H, Zhang Z. Probe the function of histone lysine 36 methylation using histone H3 lysine 36 to methionine mutant transgene in mammalian cells. Cell Cycle, 2017, 16(19): 1781-1789.
Fang D*, Gan H*, Lee J*, Han J*, Wang Z*, Riester S, Jin L, Chen J, Zhou H, Wang J, Zhang H, Yang N, Bradley E, Ho T, Rubin B, Bridge J, Thibodeau S, Ordog T, Chen Y, Wijnen A, Oliveira A, Xu R, Westerdorf J, Zhang Z. The histone H3.3K36M mutation reprograms the epigenome of chondroblastomas. Science, 2016, 352(6291): 1344-1348.
Hashizume R, Andor N, Ihara Y, Lerner R, Gan H, Chen X, Fang D, Huang X, Tom MW, Ngo V, Solomon D, Mueller S, Paris PL, Zhang Z, Petritsch C, Gupta N, Waldman TA, James CD. Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nature Medicine, 2014, doi:10.1038/nm.3716.
Pan C, Fang D, Xu G, Liang J, Zhang G, Wang H, Xie L, Zhang R. A novel acidic matrix protein, PfN44, stabilizes magnesium calcite to inhibit the crystallization of aragonite. Journal of Biological Chemistry, 2014: 289(5), 2776-87.
Chan KM*, Han J*, Fang D*, Gan H, Zhang Z. A lesson learned from the H3.3K27M mutation found in pediatric glioma: A new approach to the study of the function of histone modifications in vivo. Cell Cycle, 2013:12:2546 – 2552.
Chan KM*, Fang D*, Gan H, Hashizume R, Yu C, Schroeder M, Gupta N, Mueller S, James CD, Jenkins R, Sarkaria J, Zhang Z. The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression. Genes and Development, 2013, 27(9):985-990.
Fang D, Pan C, Lin HJ, Lin Y, Zhang GY, Wang HZ, He MX, Xie LP, Zhang RQ. Novel Basic Protein, PfN23, Functions as a Key Macromolecule during Nacre Formation. Journal of Biological Chemistry, 2012: 287(19), 15776–15785.
Fang D, Pan C, Lin HJ, Lin Y, Xu GR, Zhang GY, Wang HZ, Xie LP, Zhang RQ. Ubiquitylation Functions in the Calcium Carbonate Biomineralization in the Extracellular Matrix. PLOS ONE, 2012: 7(4): e35715.
Fang D, Xu GR, Hu YL, Pan C, Xie LP, Zhang, RQ. Identification of genes directly involved in shell formation and their functions in pearl oyster, Pinctada fucata. PLOS ONE, 2011: 6(7): e21860.