Steroid hormones act through a family of transcription factors that are able to initiate genetic programs associated with virtually all aspects of physiology. Receptors respond to steroid binding by initiating a cascade of events leading to the activation or repression of target genes. These genetic programs are tightly regulated through various steps of this activation process including receptor localization, DNA binding, cofactor binding, and chromatin reorganization. These mechanisms of control are frequently deregulated in cancers, most notably breast and prostate. My group focuses on the molecular mechanisms governing the control of receptor specificity and identifying the changes that occur in disease states.
A particular interest of my group is the potential of environmental compounds known as endocrine disruptors to influence estrogen receptor activity. Both man-made, industrial chemicals, such as bisphenol A, and naturally occurring plant compounds are able to bind and activate the estrogen receptor in a manner similar to the canonical ligand, estradiol. Nonetheless, activation of the receptor by these alternative ligands results in different transcriptional programs. One aim of my group is to dissect the mechanistic differences of activation by these ligands with the hope of better assessing the risk of exposure.
Burd CJ, Archer TK. Chromatinarchitecture defines the glucocorticoid response. Mol Cell Endocrinol. 2013 Mar 29. doi:pii: S0303-7207(13)00116-0. 10.1016/j.mce.2013.03.020. [Epub ahead of print] PubMed PMID: 23545159.
Augello MA, Burd CJ, Birbe R, McNair C, Ertel A, Magee MS, Frigo DE, Wilder-Romans K, Shilkrut M, Han S, Jernigan DL, Dean JL, Fatatis A, McDonnell DP, Visakorpi T, Feng FY, Knudsen KE. Convergence of oncogenic and hormone receptor pathways promotes metastatic phenotypes. J Clin Invest. 2013 Jan 2;123(1):493-508. doi: 10.1172/JCI64750. Epub 2012 Dec 21. PubMed PMID: 23257359; PubMed Central PMCID: PMC3533295
Burd CJ, Ward JM, Crusselle-Davis VJ, Kissling GE, Phadke D, Shah RR, Archer TK: Analysis of Chromatin Dynamics during Glucocorticoid Receptor Activation. Mol Cell Biol 2012;32:1805-1817. PMID: 22451486
Comstock CE, Augello MA, Schiewer MJ, Karch J, Burd CJ, Ertel A, Knudsen ES, Jessen WJ, Aronow BJ, Knudsen KE: Cyclin D1 is a selective modifier of androgen-dependent signaling and androgen receptor function. J Biol Chem 2011;286:8117-8127. PMID: 21212260
Burd CJ, Kinyamu HK, Miller FW, Archer TK: UV radiation regulates Mi-2 through protein translation and stability. J Biol Chem 2008;283:34976-34982. PMID: 18922793
Wang Y, Dean JL, Millar EK, Tran TH, McNeil CM, Burd CJ, Henshall SM, Utama FE, Witkiewicz A, Rui H, Sutherland RL, Knudsen KE, Knudsen ES: Cyclin D1b is aberrantly regulated in response to therapeutic challenge and promotes resistance to estrogen antagonists. Cancer Res 2008;68:5628-5638. PMID: 18632615
Olshavsky NA, Groh EM, Comstock CE, Morey LM, Wang Y, Revelo MP, Burd C, Meller J, Knudsen KE: Cyclin D3 action in androgen receptor regulation and prostate cancer. Oncogene 2008;27:3111-3121. PMID: 18084330
Burd CJ, Petre CE, Morey LM, Wang Y, Revelo MP, Haiman CA, Lu S, Fenoglio-Preiser CM, Li J, Knudsen ES, Wong J, Knudsen KE: Cyclin D1b variant influences prostate cancer growth through aberrant androgen receptor regulation. Proc Natl Acad Sci U S A 2006;103:2190-2195. PMID: 16461912
Petre-Draviam CE, Williams EB, Burd CJ, Gladden A, Moghadam H, Meller J, Diehl JA, Knudsen KE: A central domain of cyclin D1 mediates nuclear receptor corepressor activity. Oncogene 2005;24:431-444. PMID: 15558026
Link KA, Burd CJ, Williams E, Marshall T, Rosson G, Henry E, Weissman B, Knudsen KE: BAF57 governs androgen receptor action and androgen-dependent proliferation through SWI/SNF. Mol Cell Biol 2005;25:2200-2215. PMID: 15743818
Burd CJ, Petre CE, Moghadam H, Wilson EM, Knudsen KE: Cyclin D1 binding to the androgen receptor (AR) NH2-terminal domain inhibits activation function 2 association and reveals dual roles for AR corepression. Mol Endocrinol 2005;19:607-620. PMID: 15539430
Singleton DW, Feng Y, Burd CJ, Khan SA: Nongenomic activity and subsequent c-fos induction by estrogen receptor ligands are not sufficient to promote deoxyribonucleic acid synthesis in human endometrial adenocarcinoma cells. Endocrinology 2003;144:121-128.PMID: 12488337