Hai Yan

Hai Yan
Henry S. Friedman Professor of Neuro-Oncology in the School of Medicine
CMB - Clinical/Other
DSCB - Neural Development
Third Year Mentor - Molmed - Regenerative Medicine Track
Campus mail: 199B MSRB, Research Drive, Durham, NC 27710
Phone: (919) 668-7850

Our research activities center on the molecular genetics and biology of cancer with a focus on the identification, characterization, and therapeutic targeting of driver mutations involved in the genesis and progression of brain cancers.  Gliomas are the most common type of primary brain tumor. Through genomic studies, we have identified mutations in IDH1 and IDH2 in 70% of progressive malignant gliomas. These are somatic missense mutations that alter a conserved arginine residue and gain a neomorphic activity. A new metabolite produced by the glioma cells impacts on chromatin modulation and genome methylation.  Malignant cells must maintain their telomeres. We identified several different tumor types exhibiting a high frequency of TERT promoter mutations, including several glioma subtypes. Conversely, we found a low frequency of TERT promoter mutations in many common epithelial tumors.  In gliomas, we found that TERT promoter mutations were mutually exclusive with ATRX alterations, which are associated with activation of the ALT pathway for telomere maintenance. These findings show that TERT promoter mutations are frequent driver events in many human cancers, particularly those that arise from tissues with low rates of self-renewal. Our long-term goal is to develop a novel molecular-based glioma classification system and a targeted therapy on the basis of IDH1 and TERT mutations. To provide novel avenues for development of anticancer therapeutics, studies involving cell line and animal models, enzymatic study, metabolome and epigenome, are being investigated to determine the consequences of IDH1 and TERT mutations on cancer cells.

Education and Training

  • Beijing Medical University (China), M.D. 1991
  • Columbia University, Ph.D. 1997
  • Johns Hopkins University, Research Associate, Howard Hughes Institute
  • Thomas Jefferson University, Faculty, Research Associate, Molecular Genetics

Publications

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