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Chris Vakoc

Christopher Vakoc

Professor

M.D., Ph.D., University of Pennsylvania, 2007

vakoc@cshl.edu | (516) 367-5045

Vakoc Lab

Cancer cells achieve their pathogenicity by changing which genes are on and off. To maintain these changes in gene expression, cancer cells rely on proteins that interact with DNA or modify chromatin. My group investigates how such factors sustain the aberrant capabilities of cancer cells, thereby identifying new therapeutic targets.

Cancer can be understood as a disease of dysfunctional gene expression control. Research in Chris Vakoc’s lab investigates how transcription factors and chromatin regulators cooperate to control gene expression and maintain the cancer cell state. This work makes extensive use of genetic screens to reveal cancer-specific functions for transcriptional regulators, as well as genomic and biochemical approaches to identify molecular mechanisms. One theme that has emerged from their efforts is that blood cancers are often vulnerable to targeting transcriptional coactivators, such as BRD4 and the SWI/SNF chromatin remodeling complex. Vakoc’s team demonstrated that chemical inhibition of BRD4 exhibits therapeutic effects in mouse models of leukemia, a finding that has motivated ongoing clinical trials in human leukemia patients. The Vakoc lab has also developed a CRISPR-Cas9 screening approach that can reveal individual protein domains that sustain cancer cells. Their lab is now deploying this technology in a diverse array of human cancers to reveal therapeutic opportunities and basic mechanisms of cancer gene control.

AACR Outstanding Achievement in Cancer Research Award 
Forbeck Scholar Award
"V Scholar" by The V Foundation for Cancer Research
Burroughs Welcome Fund Career Award for Medical Scientists
Pershing Square Sohn Prize
Leukemia and Lymphoma Society Scholar Award

Roe, J. S. and Hwang, C. I. and Somerville, T. D. D. and Milazzo, J. P. and Lee, E. J. and Da Silva, B. and Maiorino, L. and Tiriac, H. and Young, C. M. and Miyabayashi, K. and Filippini, D. and Creighton, B. and Burkhart, R. A. and Buscaglia, J. M. and Kim, E. J. and Grem, J. L. and Lazenby, A. J. and Grunkemeyer, J. A. and Hollingsworth, M. A. and Grandgenett, P. M. and Egeblad, M. and Park, Y. and Tuveson, D. A. and Vakoc, C. R. (2017) Enhancer Reprogramming Promotes Pancreatic Cancer Metastasis. Cell, 170(5) pp. 875-888.

Hohmann, A. F. and Martin, L. J. and Minder, J. L. and Roe, J. S. and Shi, J. and Steurer, S. and Bader, G. and McConnell, D. and Pearson, M. and Gerstberger, T. and Gottschamel, T. and Thompson, D. and Suzuki, Y. and Koegl, M. and Vakoc, C. R. (2016) Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition. Nat Chem Biol, 12(9) pp. 672-9.

Shen, Chen and Ipsaro, Jonathan J and Shi, Junwei and Milazzo, Joseph P and Wang, Eric and Roe, Jae-Seok and Suzuki, Yutaka and Pappin, Darryl J and Joshua-Tor, Leemor and Vakoc, Christopher R (2015) NSD3-Short Is an Adaptor Protein that Couples BRD4 to the CHD8 Chromatin Remodeler. Molecular Cell, 60(6) pp. 847-859.

Shi, J. and Wang, E. and Milazzo, J. P. and Wang, Z. and Kinney, J. B. and Vakoc, C. R. (2015) Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains. Nat Biotechnol, 33(6) pp. 661-67.

Zuber, J. and Shi, J. and Wang, E. and Rappaport, A. R. and Herrmann, H. and Sison, E. A. and Magoon, D. and Qi, J. and Blatt, K. and Wunderlich, M. and Taylor, M. J. and Johns, C. and Chicas, A. and Mulloy, J. C. and Kogan, S. C. and Brown, P. and Valent, P. and Bradner, J. E. and Lowe, S. W. and Vakoc, C. R. (2011) RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature, 478(7370) pp. 524-528.

Additional materials of the author at
CSHL Institutional Repository