Researcher Profile

Researcher Profile

Gregory Yochum, PhD

Gregory Yochum, PhD

Associate Professor, Department of Biochemistry and Molecular Biology
Associate Professor, Department of Surgery
Scientific Program:Mechanisms of Carcinogenesis
gsy3@psu.edu

Research Interests

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.

  • Catenins
  • Colorectal Neoplasms
  • Transcription Factors
  • Chromatin
  • DNA
  • Gene Expression
  • Genes
  • Diverticulitis
  • Proteins
  • TCF Transcription Factors
  • Carcinogenesis
  • Wnt Signaling Pathway

Recent Publications

2019

Matthews, SM, Eshelman, MA, Berg, A, Koltun, W & Yochum, G 2019, 'The Crohn’s disease associated SNP rs6651252 impacts MYC gene expression in human colonic epithelial cells' PloS one, vol. 14, no. 2, e0212850. https://doi.org/10.1371/journal.pone.0212850

2018

Schieffer, KM, Kline, BP, Harris, LR, Deiling, S, Koltun, W & Yochum, G 2018, 'A differential host response to viral infection defines a subset of earlier-onset diverticulitis patients', Journal of Gastrointestinal and Liver Diseases, vol. 27, no. 3, pp. 249-255. https://doi.org/10.15403/jgld.2014.1121.273.sch
Kline, BP, Schieffer, KM, Choi, CS, Connelly, T, Chen, J, Harris, L, Deiling, S, Yochum, G & Koltun, W 2018, 'Multifocal Versus Conventional Unifocal Diverticulitis: A Comparison of Clinical and Transcriptomic Characteristics', Digestive Diseases and Sciences. https://doi.org/10.1007/s10620-018-5403-y
Schieffer, KM, Kline, BP, Yochum, G & Koltun, W 2018, 'Pathophysiology of diverticular disease', Expert Review of Gastroenterology and Hepatology, vol. 12, no. 7, pp. 683-692. https://doi.org/10.1080/17474124.2018.1481746
Raup-Konsavage, WM, Johnson, M, Legare, CA, Yochum, G, Morgan, D & Vrana, K 2018, 'Synthetic cannabinoid activity against colorectal cancer cells', Cannabis and Cannabinoid Research, vol. 3, no. 1, pp. 272-281. https://doi.org/10.1089/can.2018.0065

2017

Schieffer, KM, Poritz, L, Yochum, G & Koltun, W 2017, 'Development of a total colectomy and ileorectal anastomosis rat model to evaluate colonic metaplasia', Journal of Surgical Research, vol. 218, pp. 217-225. https://doi.org/10.1016/j.jss.2017.05.120
Coble, JL, Yue, F, Salameh, TJ, Harris, LR, Deiling, S, Ruggiero, FM, Eshelman, MA, Yochum, GS, Koltun, WA, Gerhard, GS & Broach, JR 2017, 'Identification of a rare LAMB4 variant associated with familial diverticulitis through exome sequencing', Human Molecular Genetics, vol. 26, no. 16, ddx204, pp. 3212-3220. https://doi.org/10.1093/hmg/ddx204
Schieffer, KM, Wright, JR, Harris, LR, Deiling, S, Yang, Z, Lamendellab, R, Yochum, G & Koltun, W 2017, 'NOD2 genetic variants predispose one of two familial adenomatous polyposis siblings to pouchitis through microbiome dysbiosis' Journal of Crohn's and Colitis, vol. 11, no. 11, pp. 1393-1397. https://doi.org/10.1093/ecco-jcc/jjx083
Schieffer, KM, Choi, CS, Emrich, S, Harris, L, Deiling, S, Karamchandani, D, Salzberg, A, Imamura, Y, Yochum, G & Koltun, W 2017, 'RNA-seq implicates deregulation of the immune system in the pathogenesis of diverticulitis', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 313, no. 3, pp. G277-G284. https://doi.org/10.1152/ajpgi.00136.2017
Schieffer, KM, Bruffy, SM, Rauscher, R, Koltun, W, Yochum, G & Gallagher, CJ 2017, 'Reduced total serum bilirubin levels are associated with ulcerative colitis', PloS one, vol. 12, no. 6, e0179267. https://doi.org/10.1371/journal.pone.0179267
Eshelman, MA, Shah, M, Raup-Konsavage, WM, Rennoll, SA & Yochum, G 2017, 'TCF7L1 recruits CtBP and HDAC1 to repress DICKKOPF4 gene expression in human colorectal cancer cells', Biochemical and Biophysical Research Communications, vol. 487, no. 3, pp. 716-722. https://doi.org/10.1016/j.bbrc.2017.04.123
Schieffer, KM, Sabey, K, Wright, JR, Toole, DR, Drucker, R, Tokarev, V, Harris, LR, Deiling, S, Eshelman, MA, Hegarty, JP, Yochum, G, Koltun, W, Lamendella, R & Stewart, D 2017, 'The Microbial Ecosystem Distinguishes Chronically Diseased Tissue from Adjacent Tissue in the Sigmoid Colon of Chronic, Recurrent Diverticulitis Patients', Scientific reports, vol. 7, no. 1, 8467. https://doi.org/10.1038/s41598-017-06787-8

2016

Raup-Konsavage, WM, Cooper, T & Yochum, G 2016, 'A Role for MYC in Lithium-Stimulated Repair of the Colonic Epithelium After DSS-Induced Damage in Mice', Digestive Diseases and Sciences, vol. 61, no. 2, pp. 410-422. https://doi.org/10.1007/s10620-015-3852-0
Song, C, Pan, X, Ge, Z, Gowda, C, Ding, Y, Li, H, Li, Z, Yochum, G, Muschen, M, Li, Q, Payne, KJ & Dovat, S 2016, 'Epigenetic regulation of gene expression by Ikaros, HDAC1 and Casein Kinase II in leukemia', Leukemia, vol. 30, no. 6, pp. 1436-1440. https://doi.org/10.1038/leu.2015.331
Schieffer, KM, Williams, E, Yochum, G & Koltun, W 2016, 'Review article: the pathogenesis of pouchitis', Alimentary Pharmacology and Therapeutics, vol. 44, no. 8, pp. 817-835. https://doi.org/10.1111/apt.13780
Rennoll, SA, Eshelman, MA, Raup-Konsavage, WM, Imamura, Y & Yochum, G 2016, 'The MYC 3′ Wnt-responsive element drives oncogenic MYC expression in human colorectal cancer cells', Cancers, vol. 8, no. 5, 52. https://doi.org/10.3390/cancers8050052
Eshelman, MA & Yochum, G 2016, 'The Wnt/β-catenin pathway is activated by miR-1246 in liver cancer stem cells', Translational Cancer Research, vol. 5, pp. S1457-S1460. https://doi.org/10.21037/tcr.2016.12.57

2015

Shah, M, Rennoll, SA, Raup-Konsavage, WM & Yochum, G 2015, 'A dynamic exchange of TCF3 and TCF4 transcription factors controls MYC expression in colorectal cancer cells' Cell Cycle, vol. 14, no. 3, pp. 232-332. https://doi.org/10.4161/15384101.2014.980643

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