Qin Yan PhD
Assistant Professor of Pathology
Epigenetics; Transcription regulation; Cancer biology; Stem cell biology
Stable inheritance of epigenetic states is essential for the maintenance of tissue and cell type specific functions. Aberrations of epigenetic regulation often lead to cancer and other human diseases. Our laboratory is interested in epigenetic regulation by histone demethylases in cancer and stem cells. In particular, we focus on the roles and regulatory mechanisms of histone demethylases for tri- methylated lysine 4 in histone H3 (H3K4me3), the epigenetic mark for transcriptionally active chromatin. We have previously showed RBP2 is one of the first known histone demethylases for H3K4me3. Using the RBP2 knockout mouse model, we further showed that loss of RBP2 inhibits tumorigenesis in two genetically-engineered mouse models. We are currently studying how this enzyme contributes to oncogenesis using a combination of biochemical, molecular biological, cell biological and mouse genetic approaches. We are also investigating the roles of another H3K4me3 histone demethylase PLU-1. These enzymes are potential drug targets for epigenetic therapies against cancer, therefore we have developed first generation inhibitors against these enzymes.
- Sayegh J, Cao J, Zou MR, Morales A, Blair LP, Norcia M, Hoyer D, Tackett AJ, Merkel J, Yan Q. Identification of Small Molecule Inhibitors of Jumonji AT-Rich Interactive Domain 1B (JARID1B) Histone Demethylase by a Sensitive High Throughput Screen. J Biol Chem. 2013; doi: 10.1074/jbc.M112.419861.
- Blair LP, Yan Q. Epigenetic mechanisms in commonly occurring cancers. DNA and Cell Biology, Special issue on "Epigenetics: Methylation, Chromatin, and Beyond", 31(S1): S-49-S-61. doi: 10.1089/dna.2012.1654. (2012)
- Lin W, Cao J, Liu J, Beshiri ML, Fujiwara Y, Francis J, Cherniack AD, Geisen C, Blair LP, Zou MR, Shen X, Kawamori D, Liu Z, Grisanzio C, Watanabe H, Minamishima YA, Zhang Q, Kulkarni RN, Signoretti S, Rodig SJ, Bronson RT, Orkin SH, Tuck DP, Benevolenskaya EV, Meyerson M, Kaelin WG, and Yan Q. Loss of the RBP2 histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1. PNAS, doi: 10.1073/pnas.1110104108 (2011)
- Blair LP, Cao J, Zou MR, Sayegh J, and Yan Q. Epigenetic regulation by lysine demethylase 5 (KDM5) in cancer, Cancers, 3:1383-404 (2011)
- Klose RJ*, Yan Q*, Tothova Z, Yamane K, Erdjument-Bromage H, Tempst P, Gilliland DG, Zhang Y, Kaelin WG. The retinoblastoma binding protein RBP2 is an H3K4 demethylase. Cell. 128:889-900 (2007) *equal contribution
- Yan Q, Bartz S, Mao M, Li L, Kaelin WG. The HIF2alpha N-terminal and C-terminal transactivation domains cooperate to promote renal tumorigenesis in vivo. Mol Cell Biol. 27:2092-102 (2007)