Christy R. Hagan, Ph.D.
Biochemistry and Molecular Biology
Colorado College, Colorado Springs, CO, B.A. in Biochemistry, cum laude, 1998
Human Gene Therapy Research Institute, Des Moines, IA, Pre-Doctoral Fellow, 1998 - 2000
University of Chicago, Chicago IL, PH.D. in Cancer Biology, 2006
Northwestern University, Postdoctoral Fellowship, 2006 – 2008
University of Minnesota, Postdoctoral Fellowship, 2008-2014
University of Kansas Medical Center, Kansas City, KS, Assistant Professor, 2015 – present
Publications: Click here
Office: 1063 Hemenway
Lab: 1022 Hemenway
My lab studies the role of hormones in breast cancer. In particular, we are interested in how the ovarian steroid hormone, progesterone, works together with its receptor, the progesterone receptor (PR), to influence breast cancer biology. Mounting clinical data continues to implicate progesterone and PR in breast cancer progression. Upon diagnosis, nearly 70% of breast cancers express PR and the estrogen receptor (ER). In contrast, only 7-10% of normal luminal epithelial cells express ER and PR. ER action in breast cancer has been well studied and as a result, ER has proven to be an excellent target for current endocrine-based therapies. However, despite convincing clinical trial data implicating progesterone in the development of invasive breast cancer, the role of progesterone/PR in breast cancer has been largely understudied. Despite maintaining receptor (ER/PR) expression, many breast cancer patients eventually progress to hormone-independence, failing current (largely ER/estrogen based) endocrine therapies. Therefore, ER-independent functions of PR are of great clinical interest.
Moreover, many protein kinases (MAPK, ck2) known to modify and activate PR have been shown to be dysregulated in breast cancer. These same kinases are also known contributors to breast cancer development/progression. This creates a scenario whereby PR can be inappropriately activated by aberrant kinases in the absence of hormones (progesterone) normally required for full receptor activation. PR is highly post-translationally modified, largely though phosphorylation. These phosphorylation events have been shown to dramatically alter reception function, turnover, subcellular localization, protein binding partners, and recruitment to specific gene regulatory regions. PR modification through phosphorylation is a potent way to alter PR action and may in part explain why somatic mutations are not often observed in breast cancer. We are very interested in understanding how post-translational modifications determine genomic PR binding profiles, and subsequently, highly context-specific transcriptional programs.
Finally, preliminary data from our lab suggests that PR, together with the potent pro-inflammatory signaling molecule STAT5A, may drive pro-inflammatory gene signatures in breast cancer. Understanding cross-talk between PR and inflammation is critical to developing better treatments, and could expose a novel mechanism through which PR drives breast cancer growth that may be exploited for novel PR-based endocrine therapies.