|Institution||College of Medicine|
|Department||Biochemistry and Molecular Biology|
|Address||500 University Drive Hershey PA 17033|
Assistant Professor of Biochemistry and Molecular Biology
SECONDARY APPOINTMENT(S)/ INSTITUTE(S)/ CENTER(S):
The Huck Institutes of the Life Sciences
The Penn State Hershey Cancer Institute
GRADUATE PROGRAM AFFILIATIONS
Biomedical Sciences: Option in Biochemistry & Molecular Genetics
BS Biology, Bucknell University, 1994
Ph.D. Oncological Sciences, University of Utah, 2002
Post-doctoral training, Oregon Health & Sciences University, 2002-2009
The Wnt/ß-catenin signaling pathway is essential for normal intestinal growth and development and inappropriate activation of this pathway is associated with colon cancer. Mutations in components of this signaling pathway lead to high levels of the ß-catenin transcriptional co-activator in the nucleus. Nuclear ß-catenin associates with members of the T-cell factor/ lymphoid enhancer factor (TCF/LEF) family of sequence-specific transcription factors. ß-Catenin/TCF complexes activate target gene expression through recruitment of factors that remodel or modify chromatin structure. Because mutations in Wnt/ß-catenin signaling components are amongst the earliest detected lesions as cells progress from normal colonic epithelial cells to a transformed phenotype, we believe it is essential to identify direct ß-catenin target genes in order to understand the etiology of colon cancer.
My lab uses unbiased and genome-wide methodologies to identify direct ß-catenin binding sites in human colon cancer cell lines. We then use a combination of genetic and molecular biological approaches to determine which putative binding sites confer target gene activation in a Wnt/ß-catenin dependent manner. Using ß-catenin chromatin immunoprecipitation coupled with Serial Analysis of Chromatin Occupancy (SACO), we previously identified a novel Wnt responsive enhancer element (WRE) that resides 1.4 kb downstream of the c-Myc gene. We named this element the MYC 3'WRE. MYC is a proto-oncogene that promotes cell growth and proliferation by controlling expression of genes that regulate metabolism and cell cycle progression. We have shown that the MYC 3' WRE is the principal regulatory element that controls MYC expression in response to Wnt/ß-catenin and mitogen signaling in human colon cancer cells. We are currently determining whether this MYC 3' WRE is required for homeostasis in the mouse intestinal tract. In addition, we are employing ChIP coupled with massively parallel sequencing (ChIP-Seq) to profile ß-catenin binding sites in order to identify those targets whose ß-catenin occupancy changes in response to mitogen signaling.
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