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
  • Genes
  • Colorectal Neoplasms
  • Diverticulitis
  • Gene Expression
  • Chromatin
  • DNA
  • Transcription Factors
  • Proteins
  • Crohn Disease
  • Ulcerative Colitis
  • TCF Transcription Factors

Recent Publications

2021

Ganapathy, AS, Saha, K, Suchanec, E, Singh, V, Verma, A, Yochum, G, Koltun, W, Nighot, M, Ma, T & Nighot, P 2021, 'AP2M1 mediates autophagy-induced CLDN2 (claudin 2) degradation through endocytosis and interaction with LC3 and reduces intestinal epithelial tight junction permeability', Autophagy. https://doi.org/10.1080/15548627.2021.2016233
Schieffer, KM, Emrich, SM, Yochum, GS & Koltun, WA 2021, 'CD163L1+CXCL10+ Macrophages are Enriched Within Colonic Lamina Propria of Diverticulitis Patients', Journal of Surgical Research, vol. 267, pp. 527-535. https://doi.org/10.1016/j.jss.2021.06.016
Kline, BP, Yochum, GS, Brinton, DL, Schieffer, KM, Weaver, T, Harris, L, Deiling, S, Berg, AS & Koltun, WA 2021, 'COLQ and ARHGAP15 are associated with diverticular disease and are expressed in the colon', Journal of Surgical Research, vol. 267, pp. 397-403. https://doi.org/10.1016/j.jss.2021.05.043
Kline, BP, Weaver, T, Brinton, DL, Harris, L, Yochum, GS, Berg, AS & Koltun, WA 2021, 'Clinical and Genetic Factors Impact Time to Surgical Recurrence After Ileocolectomy for Crohn's Disease', Annals of surgery, vol. 274, no. 2, pp. 346-351. https://doi.org/10.1097/SLA.0000000000003660
Grim, C, Noble, R, Uribe, G, Khanipov, K, Johnson, P, Koltun, WA, Watts, T, Fofanov, Y, Yochum, GS, Powell, DW, Beswick, EJ & Pinchuk, IV 2021, 'Impairment of Tissue-Resident Mesenchymal Stem Cells in Chronic Ulcerative Colitis and Crohn's Disease', Journal of Crohn's and Colitis, vol. 15, no. 8, pp. 1362-1375. https://doi.org/10.1093/ecco-jcc/jjab001
Teye, EK, Lu, S, Chen, F, Yang, W, Abraham, T, Stairs, DB, Wang, HG, Yochum, GS, Brodsky, RA & Pu, JJ 2021, 'PIGN spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression', Scientific reports, vol. 11, no. 1, 19022. https://doi.org/10.1038/s41598-021-98218-y
Jeganathan, NA, Davenport, ER, Yochum, GS & Koltun, WA 2021, 'The microbiome of diverticulitis', Current Opinion in Physiology, vol. 22, 100452. https://doi.org/10.1016/j.cophys.2021.06.006

2020

Kline, BP, Weaver, T, Brinton, DL, Deiling, S, Yochum, GS, Berg, AS & Koltun, WA 2020, 'Clinical and Genetic Factors Associated With Complications After Crohn's Ileocolectomy', Diseases of the colon and rectum, vol. 63, no. 3, pp. 357-364. https://doi.org/10.1097/DCR.0000000000001574
Pathak, T, Gueguinou, M, Walter, V, Delierneux, C, Johnson, MT, Zhang, X, Xin, P, Yoast, RE, Emrich, SM, Yochum, GS, Sekler, I, Koltun, WA, Gill, DL, Hempel, N & Trebak, M 2020, 'Dichotomous role of the human mitochondrial na+ /ca2+ /li+ exchanger nclx in colorectal cancer growth and metastasis', eLife, vol. 9, e59686, pp. 1-41. https://doi.org/10.7554/ELIFE.59686
Rawat, M, Nighot, M, Al-Sadi, R, Gupta, Y, Viszwapriya, D, Yochum, G, Koltun, W & Ma, TY 2020, 'IL1B Increases Intestinal Tight Junction Permeability by Up-regulation of MIR200C-3p, Which Degrades Occludin mRNA', Gastroenterology, vol. 159, no. 4, pp. 1375-1389. https://doi.org/10.1053/j.gastro.2020.06.038
Aguirre, JE, Beswick, EJ, Grim, C, Uribe, G, Tafoya, M, Palma, GC, Samedi, V, McKee, R, Villeger, R, Fofanov, Y, Cong, Y, Yochum, G, Koltun, W, Powell, D & Pinchuk, IV 2020, 'Matrix metalloproteinases cleave membrane-bound PD-L1 on CD90+ (myo-)fibroblasts in Crohn’s disease and regulate Th1/Th17 cell responses', International immunology, vol. 32, no. 1, pp. 57-68. https://doi.org/10.1093/intimm/dxz060
Singh, V, Gowda, CP, Singh, V, Ganapathy, AS, Karamchandani, DM, Eshelman, MA, Yochum, GS, Nighot, P & Spiegelman, VS 2020, 'The mRNA-binding protein IGF2BP1 maintains intestinal barrier function by up-regulating Occludin expression', Journal of Biological Chemistry, vol. 295, no. 25, pp. 8602-8612. https://doi.org/10.1074/jbc.ac120.013646
Eshelman, MA, Harris, L, Deiling, S, Koltun, WA, Jeganathan, NA & Yochum, GS 2020, 'Transcriptomic analysis of ileal tissue from crohn’s disease patients identifies extracellular matrix genes that distinguish individuals by age at diagnosis', Physiological genomics, vol. 52, no. 10, pp. 478-484. https://doi.org/10.1152/physiolgenomics.00062.2020

2019

Eshelman, MA, Jeganathan, NA, Schieffer, KM, Kline, BP, Mendenhall, M, Deiling, S, Harris, L, Koltun, WA & Yochum, GS 2019, 'Elevated colonic mucin expression correlates with extended time to surgery for ulcerative colitis patients', Journal of Gastrointestinal and Liver Diseases, vol. 28, no. 4, pp. 405-413. https://doi.org/10.15403/jgld-250
Matthews, SM, Eshelman, MA, Berg, AS, Koltun, WA & Yochum, GS 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
Eshelman, MA, Matthews, SM, Schleicher, EM, Fleeman, RM, Kawasawa, YI, Stumpo, DJ, Blackshear, PJ, Koltun, WA, Ishmael, FT & Yochum, GS 2019, 'Tristetraprolin targets Nos2 expression in the colonic epithelium', Scientific reports, vol. 9, no. 1, 14413. https://doi.org/10.1038/s41598-019-50957-9

2018

Schieffer, KM, Kline, BP, Harris, LR, Deiling, S, Koltun, WA & Yochum, GS 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, GS & Koltun, WA 2019, 'Multifocal Versus Conventional Unifocal Diverticulitis: A Comparison of Clinical and Transcriptomic Characteristics', Digestive Diseases and Sciences, vol. 64, no. 11, pp. 3143-3151. 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, GS, Morgan, DJ & Vrana, KE 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

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