Emily C. Dykhuizen
2002-2008 PhD (chemistry) UW-Madison under Laura L. Kiessling
2009-2013 Postdoc (chromatin biology) Stanford University under Gerald R. Crabtree
See our website for more information: www.dykhuizenlab.com
Recent cancer genome sequencing studies have uncovered frequent mutations in genes encoding subunits of nuclear protein complexes involved in epigenetic regulation. We are interested in using a combination of chemical and biochemical techniques to uncover the role of chromatin structure in tumor suppression. Uncovering the mechanisms of these complexes will reveal potential therapeutic avenues for cancers that currently have few therapeutic options, such as renal clear cell carcinoma and ovarian clear cell carcinoma. Three areas of research we are currently pursuing are:
1- Proteomic analysis of chromatin modifying complexes. While different subunits of the SWI/SNF chromatin remodeling complexes are mutated in approximately 20% of human malignancies, in any particular cancer the mutations are often found only in one particular subunit. Cell type specific expression of homologous subunits or interaction with cell type specific factors may explain this phenomenon. We plan to use mass spec to analyze the complex subunits and associated factors in cancer to define cancer-specific SWI/SNF and polcomb repressive complexes (PRC).
2-High throughput screening to identify inhibitors of chromatin regulators. Aberrant function of chromatin remodelers can occur upon the deletion of a tumor-suppressive particular subunit. These tumors are dependent on the function of the remaining complex, making it a potential drug target. In addition, we are interested in developing inhibitors of chromatin-binding domains important in the progression and chemoresistance of cancer.
3-Elucidating the function and genome-wide targeting of proteins containing chromatin binding domains, such as bromodomains, PHD domains and chromodomains. We wish to understand how the targeting domains found in subunits of chromatin remodeling complexes contribute to their biological function. We plan to identify histone modifications bound by these domains and to relate this information to genome wide ChIP-seq studies performed with and without deletions of these domains. Through these studies we hope to identify if the deletion of specific subunits of chromatin remodelers in cancer leads to changes in targeting across the genome and a subsequent alteration in the transcription of known oncogenes or tumor suppressors.
Porter EG, Dykhuizen EC. J Biol Chem. 2017 Jan 4. pii: jbc.M116.746875. doi: 10.1074/jbc.M116.746875. [Epub ahead of print]
Connelly KE, Martin EC, Dykhuizen EC. Yale J Biol Med. 2016 Dec 23;89(4):431-440.
Connelly KE, Dykhuizen EC. Biochim Biophys Acta. 2016 Dec 20;1860(2):233-245. doi: 10.1016/j.bbagrm.2016.12.006. [Epub ahead of print] Review.
Chowdhury B, Porter EG, Stewart JC, Ferreira CR, Schipma MJ, Dykhuizen EC. PLoS One. 2016 Apr 21;11(4):e0153718. doi: 10.1371/journal.pone.0153718.
Stoszko M, De Crignis E, Rokx C, Khalid MM, Lungu C, Palstra RJ, Kan TW, Boucher C, Verbon A, Dykhuizen EC, Mahmoudi T. EBioMedicine. 2015 Nov 27;3:108-21. doi: 10.1016/j.ebiom.2015.11.047.
Dykhuizen EC, Hargreaves DC, Miller EL, Cui K, Korshunov A, Kool M, Pfister S, Cho YJ, Zhao K, Crabtree GR. Nature. 2013 May 30;497(7451):624-7. doi: 10.1038/nature12146.
Dykhuizen EC, Carmody LC, Tolliday N, Crabtree GR, Palmer MA. J Biomol Screen. 2012 Oct;17(9):1221-30.
Dykhuizen EC, Kiessling LL. Org Lett. 2009 Jan 1;11(1):193-6. doi: 10.1021/ol802094p.
Dykhuizen EC, May JF, Tongpenyai A, Kiessling LL. J Am Chem Soc. 2008 May 28;130(21):6706-7. doi: 10.1021/ja8018687.
Carlson CB, Mowery P, Owen RM, Dykhuizen EC, Kiessling LL. ACS Chem Biol. 2007 Feb 20;2(2):119-27.
Stevens SL, Shaw TE, Dykhuizen E, Lessov NS, Hill JK, Wurst W, Stenzel-Poore MP. J Cereb Blood Flow Metab. 2003 Oct;23(10):1151-9.