Walker, Cheryl L.

Walker, Cheryl L. Ph.D.

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Research Interests

Cell signaling pathways, endocrine disruptors, cellular responses to oxidative stress and DNA damage, genitourinary and female reproductive tract cancers, polycystic kidney disease (PKD), Tuberous Sclerosis Complex 2 (TSC2) tumor suppressor gene

Current Research

The current focus of my research program is to identify mechanisms responsible for the development of cancers of the male genitourinary tract (kidney and prostate) and female reproductive tract (uterus) with the goal of utilizing this information to develop new targeted therapies for these diseases. Our research is focused on:

Identifying cell signaling pathways that regulate the TSC2 tumor suppressor
TSC2 functions as the gatekeeper for mTOR signaling, a master regulator of protein synthesis and cell growth. We have found that the activity of TSC2 is regulated by AKT phosphorylation, causing TSC2 to partition out of the membrane into the cytosol, separating it from its activation partner TSC1 and its target Rheb. In addition, we have found that TSC2 is regulated by genotoxic and oxidative damage, identifying a new signaling node connecting damage response and cell growth pathways.

Elucidating how TSC2 and PKD1 interact to regulate key cellular functions
Polycystic kidney disease is the most common, potentially lethal genetic alteration in humans. The TSC2 and PKD1 genes lie adjacent to each other on chromosome 16 and are transcribed in a tail-to-tail orientation. We were the first to demonstrate that the protein products of these genes, tuberin and polycystin, are functionally related. Recently, we have found that PKD1 can modulate mTOR repression by TSC2, and studies are underway to determine the nature of this interaction and how it is regulated by cell signaling proteins

Understanding how early life exposures to endocrine disruptors in our environment promote development of cancer in adults
We have recently identified developmental programming as a novel type of gene-environment interaction that determines cancer risk in genetically susceptible individuals. We found that a brief exposure to a xenoestrogen (chemicals in our environment that mimic the female hormone estrogen) early in life while a tissue is developing can reprogram gene expression in such as way as to promote tumor development in that tissue later in adult life. We have found that epigenetic alterations, specifically alterations in patterns of histone methylation, are one mechanism by which xenoestrogens change the “methyl marks” on chromatin to induce developmental reprogramming.

Selected Publications

  1. Lu KH, Wu W, Dave B, Slomovitz BM, Burke TW, Munsell MF, Broaddus RR, Walker CL. Loss of tuberous sclerosis complex-2 function and activation of mammalian target of rapamycin signaling in endometrial carcinoma, Clin Cancer Res, 14 (9), 2543-50, 2008
  2. Short JD, Houston KD, Dere R, Cai SL, Kim J, Johnson CL, Broaddus RR, Shen J, Miyamoto S, Tamanoi F, Kwiatkowski D, Mills GB, Walker CL. AMP-activated protein kinase signaling results in cytoplasmic sequestration of p27, Cancer Res, 68 (16), 6496-506, 2008
  3. Laping NJ, Everitt JI, Frazier KS, Burgert M, Portis MJ, Cadacio C, Gold LI, Walker CL. Tumor-specific efficacy of transforming growth factor-beta RI inhibition in Eker rats, Clin Cancer Res, 13 (10), 3087-99, 2007
  4. Liang J, Shao SH, Xu ZX, Hennessy B, Ding Z, Larrea M, Kondo S, Dumont DJ, Gutterman JU, Walker CL, Slingerland JM, Mills GB. The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis, Nat Cell Biol, 9 (2), 218-24, 2007
  5. Cai SL, Tee AR, Short JD, Bergeron JM, Kim J, Shen J, Guo R, Johnson CL, Kiguchi K, Walker CL. Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning, J Cell Biol, 173 (2), 279-89, 2006
  6. Cook JD, Davis BJ, Cai SL, Barrett JC, Conti CJ, Walker CL. Interaction between genetic susceptibility and early-life environmental exposure determines tumor-suppressor-gene penetrance, Proc Natl Acad Sci U S A, 102 (24), 8644-9, 2005
  7. Walker CL, Stewart EA. Uterine fibroids: the elephant in the room, Science, 308 (5728), 1589-92, 2005
  8. Cai S, Everitt JI, Kugo H, Cook J, Kleymenova E, Walker CL. Polycystic kidney disease as a result of loss of the tuberous sclerosis 2 tumor suppressor gene during development, Am J Pathol, 162 (2), 457-68, 2003

Contact Information


Mailing Address: P.O. Box 389, Smithville, Texas 78957
Physical Address: 1808 Park Road 1C, Smithville, Texas 78957
Phone: (512) 237-9525