Dr. Gregory Yochum's research focuses on Wnt/ß-catenin signaling in intestinal homeostasis, inflammatory bowel disease (IBD) and colorectal cancer (CRC).

ß-catenin is a transcriptional co-activator that binds the T-cell factor/Lymphoid enhancer factor (TCF/Lef) family of transcription factors. TCF/ß-catenin transcription complexes associate with Wnt-responsive DNA elements (WREs) to increase expression of downstream target genes.

Much of Dr. Yochum's work has focused on the MYC proto-oncogene, where his lab has identified novel WREs that inappropriately regulate MYC expression by directly modifying the chromatin architecture at the MYC promoter region, in some cases through the formation of long-range chromatin loops. The lab uses a combination of biochemical approaches in established CRC cell lines, mouse model systems and human-derived intestinal tissues to support this research.

Current efforts in the lab are focused on how TCF/ß-catenin complex function is muted on chromatin to ensure "just-right" levels of target expression.

A second line of study centers on the function of the RNA-binding protein tristetraprolin (TTP) in the intestinal epithelium. TTP binds AU-rich elements in the 3'UTRs of target mRNAs and facilitates their degradation. The Yochum lab has uncovered a critical role of TTP in regulating the epithelial barrier in the intestine and is investigating this relationship in ulcerative colitis (UC) and CRC.

In 2016, the Yochum lab joined with Dr. Walter Koltun’s lab. Dr. Koltun, chief of Colon and Rectal Surgery in the Department of Surgery at Penn State College of Medicine, established an extensive colorectal disease and IBD biobank that contains more than 4,500 consented patients treated at Penn State Health Milton S. Hershey Medical Center for intestinal disease. In addition to serum and blood DNA from these patients, the biobank has full-thickness tissues from more than half of the patients, stored in a variety of media.

Together, the Yochum and Koltun teams are using these samples to understand the genetic basis of intestinal disease, how genetics can inform surgical decision-making and how environmental factors, including the microbiome, contributes to the disease process.