M.D., Ph.D. University of Pennsylvania, 2007
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.
Roe, Jae-Seok and Mercan, Fatih and Rivera, Keith and Pappin, Darryl J and Vakoc, Christopher R (2015) BET Bromodomain Inhibition Suppresses the Function of Hematopoietic Transcription Factors in Acute Myeloid Leukemia. Molecular Cell 58(6) pp. 1028-1036.
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
Wang, E. and Kawaoka, S. and Roe, J. S. and Shi, J. and Hohmann, A. F. and Xu, Y. and Bhagwat, A. S. and Suzuki, Y. and Kinney, J. B. and Vakoc, C. R. (2015) The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer. Elife 4
Shi, J. and Whyte, W. A. and Zepeda-Mendoza, C. J. and Milazzo, J. P. and Shen, C. and Roe, J. S. and Minder, J. L. and Mercan, F. and Wang, E. and Eckersley-Maslin, M. A. and Campbell, A. E. and Kawaoka, S. and Shareef, S. and Zhu, Z. and Kendall, J. and Muhar, M. and Haslinger, C. and Yu, M. and Roeder, R. G. and Wigler, M. A. and Blobel, G. A. and Zuber, J. and Spector, D. L. and Young, R. A. and Vakoc, C. R. (2013) Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation. Genes and Development 27(24) pp. 264-273.
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
‘Druggable’ protein complex identified as a therapeutic target in acute myeloid leukemia
Unconventional hunt for new cancer targets leads to a powerful drug candidate for leukemia
‘A’ award from Alex’s Lemonade Stand Foundation
"V Scholar" for 2012 by The V Foundation for Cancer Research