Gregory Yochum, PhD - Penn State Cancer Institute
Researcher Profile
Gregory Yochum, PhD
Associate Professor, Department of Biochemistry and Molecular Biology
Associate Professor, Department of Surgery
Associate Professor, Department of Surgery
Scientific Program:Mechanisms of Carcinogenesis
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
- Genes
- Diverticulitis
- Gene Expression
- DNA
- Chromatin
- Transcription Factors
- Proteins
- Crohn Disease
- Ulcerative Colitis
- TCF Transcription Factors
Recent Publications
2024
Ding, W, Marx, OM, Mankarious, MM, Koltun, WA & Yochum, GS 2024, 'Disease Severity Impairs Generation of Intestinal Organoid Cultures From Inflammatory Bowel Disease Patients', Journal of Surgical Research, vol. 293, pp. 187-195. https://doi.org/10.1016/j.jss.2023.08.027
Marx, OM, Mankarious, MM, Koltun, WA & Yochum, GS 2024, 'Identification of differentially expressed genes and splicing events in early-onset colorectal cancer', Frontiers in Oncology, vol. 14, 1365762. https://doi.org/10.3389/fonc.2024.1365762
King, CM, Ding, W, Eshelman, MA & Yochum, GS 2024, 'TCF7L1 regulates colorectal cancer cell migration by repressing GAS1 expression', Scientific reports, vol. 14, no. 1, 12477. https://doi.org/10.1038/s41598-024-63346-8
2023
Ganapathy, AS, Saha, K, Wang, A, Arumugam, P, Dharmaprakash, V, Yochum, G, Koltun, W, Nighot, M, Perdew, G, Thompson, TA, Ma, T & Nighot, P 2023, 'Alpha-tocopherylquinone differentially modulates claudins to enhance intestinal epithelial tight junction barrier via AhR and Nrf2 pathways', Cell Reports, vol. 42, no. 7, 112705. https://doi.org/10.1016/j.celrep.2023.112705
Saha, K, Subramenium Ganapathy, A, Wang, A, Arumugam, P, Michael Morris, N, Harris, L, Yochum, G, Koltun, W, Perdew, GH, Nighot, M, Ma, T & Nighot, P 2023, 'Alpha-tocopherylquinone-mediated activation of the Aryl Hydrocarbon Receptor regulates the production of inflammation-inducing cytokines and ameliorates intestinal inflammation', Mucosal Immunology, vol. 16, no. 6, pp. 826-842. https://doi.org/10.1016/j.mucimm.2023.09.003
Saha, K, Subramenium Ganapathy, A, Wang, A, Michael Morris, N, Suchanec, E, Ding, W, Yochum, G, Koltun, W, Nighot, M, Ma, T & Nighot, P 2023, 'Autophagy Reduces the Degradation and Promotes Membrane Localization of Occludin to Enhance the Intestinal EpithelialTight Junction Barrier against Paracellular Macromolecule Flux', Journal of Crohn's and Colitis, vol. 17, no. 3, pp. 433-449. https://doi.org/10.1093/ecco-jcc/jjac148
Finnegan, E, Ding, W, Ude, Z, Terer, S, McGivern, T, Blümel, AM, Kirwan, G, Shao, X, Genua, F, Yin, X, Kel, A, Fattah, S, Myer, PA, Cryan, SA, Prehn, JHM, O’Connor, DP, Brennan, L, Yochum, G, Marmion, CJ & Das, S 2024, 'Complexation of histone deacetylase inhibitor belinostat to Cu(II) prevents premature metabolic inactivation in vitro and demonstrates potent anti-cancer activity in vitro and ex vivo in colon cancer', Cellular oncology (Dordrecht), vol. 47, no. 2, pp. 533-553. https://doi.org/10.1007/s13402-023-00882-x
Xiao, L, Warner, B, Mallard, CG, Chung, HK, Shetty, A, Brantner, CA, Rao, JN, Yochum, GS, Koltun, WA, To, KB, Turner, DJ, Gorospe, M & Wang, JY 2023, 'Control of Paneth cell function by HuR regulates gut mucosal growth by altering stem cell activity', Life Science Alliance, vol. 6, no. 11, e202302152. https://doi.org/10.26508/lsa.202302152
Mankarious, MM, Connelly, TM, Harris, L, Deiling, S, Yochum, GS & Koltun, WA 2023, 'Creating a Surgical Biobank: The Hershey Medical Center Experience', Diseases of the colon and rectum, vol. 66, no. 9, pp. 1174-1184. https://doi.org/10.1097/DCR.0000000000002944
Sinha, S, Aizawa, S, Nakano, Y, Rialdi, A, Choi, HY, Shrestha, R, Pan, SQ, Chen, Y, Li, M, Kapelanski-Lamoureux, A, Yochum, G, Sher, L, Monga, SP, Lazaris, A, Machida, K, Karin, M, Guccione, E & Tsukamoto, H 2023, 'Hepatic stellate cell stearoyl co-A desaturase activates leukotriene B4 receptor 2 - β-catenin cascade to promote liver tumorigenesis', Nature communications, vol. 14, no. 1, 2651. https://doi.org/10.1038/s41467-023-38406-8
Nighot, M, Liao, PL, Morris, N, McCarthy, D, Dharmaprakash, V, Ullah Khan, I, Dalessio, S, Saha, K, Ganapathy, AS, Wang, A, Ding, W, Yochum, G, Koltun, W, Nighot, P & Ma, T 2023, 'Long-Term Use of Proton Pump Inhibitors Disrupts Intestinal Tight Junction Barrier and Exaggerates Experimental Colitis', Journal of Crohn's and Colitis, vol. 17, no. 4, pp. 565-579. https://doi.org/10.1093/ecco-jcc/jjac168
Panganiban, RP, Tuan, A, Hart, M, Pelton, M, Mikhail, D, Akhtar, S, Bogale, K, Deiling, S, Zhou, S, Coates, MD, Yochum, GS & Koltun, W 2023, 'Pyoderma Gangrenosum Is Associated With Increased Risk of Inflammatory Pouch-Related Complications: A Retrospective Cohort Study', Crohn's and Colitis 360, vol. 5, no. 3, otad024. https://doi.org/10.1093/crocol/otad024
King, CM, Marx, OM, Ding, W, Koltun, WA & Yochum, GS 2023, 'TCF7L1 Regulates LGR5 Expression in Colorectal Cancer Cells', Genes, vol. 14, no. 2, 481. https://doi.org/10.3390/genes14020481
Portolese, AC, McMullen, BN, Baker, SK, Chen See, JR, Yochum, GS, Koltun, WA, Lamendella, R & Jeganathan, NA 2023, 'The Microbiome of Complicated Diverticulitis: An Imbalance of Sulfur-Metabolizing Bacteria', Diseases of the colon and rectum, vol. 66, no. 5, pp. 707-715. https://doi.org/10.1097/DCR.0000000000002647
2022
Zhao, X, Yang, W, Yu, T, Yu, Y, Cui, X, Zhou, Z, Yang, H, Yu, Y, Bilotta, AJ, Yao, S, Xu, J, Zhou, J, Yochum, GS, Koltun, WA, Portolese, A, Zeng, D, Xie, J, Pinchuk, IV, Zhang, H & Cong, Y 2023, 'Th17 Cell-Derived Amphiregulin Promotes Colitis-Associated Intestinal Fibrosis Through Activation of mTOR and MEK in Intestinal Myofibroblasts', Gastroenterology, vol. 164, no. 1, pp. 89-102. https://doi.org/10.1053/j.gastro.2022.09.006
Marx, OM, Mankarious, MM, Eshelman, MA, Ding, W, Koltun, WA & Yochum, GS 2022, 'Transcriptome Analyses Identify Deregulated MYC in Early Onset Colorectal Cancer', Biomolecules, vol. 12, no. 9, 1223. https://doi.org/10.3390/biom12091223
2021
Ganapathy, AS, Saha, K, Suchanec, E, Singh, V, Verma, A, Yochum, G, Koltun, W, Nighot, M, Ma, T & Nighot, P 2022, 'AP2M1 mediates autophagy-induced CLDN2 (claudin 2) degradation through endocytosis and interaction with LC3 and reduces intestinal epithelial tight junction permeability', Autophagy, vol. 18, no. 9, pp. 2086-2103. 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