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Genetics Faculty

Zhenghe Wang
Professor/Vice Chair for Faculty Development Department of Genetics and Genome Sciences
Ph.D. Training Faculty
Department of Genetics
School of Medicine
Case Western Reserve University
Wolstein Research Building
2103 Cornell Road
Cleveland, Ohio 44106
Tel: (216) 368-0446
Fax: (216) 368-3432

About Zhenghe Wang

John Wang received his Ph.D. in Microbiology from University of Virginia in 2001 for work on the molecular mechanism of sister chromatid cohesion in yeast. He was a postdoctoral fellow with Dr. Bert Vogelstein in the Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins University, where he used high throughput sequence-based mutational analysis to identify somatic mutations in human colorectal cancer. He also dissected the APC/β-catenin pathways in colorectal cells using somatic cell knockout technique. Dr. Wang joined the Department of Genetics and the Case Comprehensive Cancer Center in August, 2005.


Dr. Wang and his research group are interested in dissecting the signaling pathways controlled by phosphatases that are mutated in cancer. The role of phosphatases in tumorigenesis is less well-defined than that of kinases. However, increasing evidence suggests that phosphatases are an important component of tumor development. We have recently identified six protein tyrosine phosphatase genes mutated in colorectal cancers using high throughput sequence-based mutational analysis. The majority of mutations in phosphatases characterized in colon cancers clearly cause inactivation of these genes suggesting that these phosphatases function as tumor suppressor genes in normal colon cells. We are currently studying the signal pathways regulated by the two frequently mutated phosphatases, PTPRT and PTPN13, using genetic and biochemical approaches to determine how these genes prevent cancer development.

These studies are part of our overall laboratory program focused on identifying novel genetic alterations, such as somatic mutations, gene amplifications and deletions, which alter critical gene functions involved in development of colon and gastric cancers.

Selected Publications

Wang Z, Li L, Guda K, Chen Z, Barnholtz-Sloan J, Park YS, Markowitz SD, Willis J (2016)
Adverse Clinical Outcome Associated With Mutations That Typify African American Colorectal Cancers.
J Natl Cancer Inst;108(12):
See PubMed abstract

Zhao Y, Scott A, Zhang P, Hao Y, Feng X, Somasundaram S, Khalil AM, Willis J, Wang Z (2016)
Regulation of paxillin-p130-PI3K-AKT signaling axis by Src and PTPRT impacts colon tumorigenesis.
See PubMed abstract

Hao Y, Samuels Y, Li Q, Krokowski D, Guan BJ, Wang C, Jin Z, Dong B, Cao B, Feng X, Xiang M, Xu C, Fink S, Meropol NJ, Xu Y, Conlon RA, Markowitz S, Kinzler KW, Velculescu VE, Brunengraber H, Willis JE, LaFramboise T, Hatzoglou M, Zhang GF, Vogelstein B, Wang Z (2016)
Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancer.
Nat Commun;7:11971
See PubMed abstract

Zhao S, Sedwick D, Wang Z (2015)
Genetic alterations of protein tyrosine phosphatases in human cancers.
See PubMed abstract

Zhang Y, Desai A, Yang SY, Bae KB, Antczak MI, Fink SP, Tiwari S, Willis JE, Williams NS, Dawson DM, Wald D, Chen WD, Wang Z, Kasturi L, Larusch GA, He L, Cominelli F, Di Martino L, Djuric Z, Milne GL, Chance M, Sanabria J, Dealwis C, Mikkola D, Naidoo J, Wei S, Tai HH, Gerson SL, Ready JM, Posner B, Willson JK, Markowitz SD (2015)
TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration.
See PubMed abstract

Guda K, Veigl ML, Varadan V, Nosrati A, Ravi L, Lutterbaugh J, Beard L, Willson JK, Sedwick WD, Wang ZJ, Molyneaux N, Miron A, Adams MD, Elston RC, Markowitz SD, Willis JE (2015)
Novel recurrently mutated genes in African American colon cancers.
Proc Natl Acad Sci U S A;112(4):1149-54
See PubMed abstract

Feng X, Scott A, Wang Y, Wang L, Zhao Y, Doerner S, Satake M, Croniger CM, Wang Z (2014)
PTPRT regulates high-fat diet-induced obesity and insulin resistance.
PLoS One;9(6):e100783
See PubMed abstract

Hao Y, Wang C, Cao B, Hirsch BM, Song J, Markowitz SD, Ewing RM, Sedwick D, Liu L, Zheng W, Wang Z (2013)
Gain of Interaction with IRS1 by p110α-Helical Domain Mutants Is Crucial for Their Oncogenic Functions.
Cancer Cell;:
See PubMed abstract

Zhang P, Guo A, Possemato A, Wang C, Beard L, Carlin C, Markowitz SD, Polakiewicz RD, Wang Z (2012)
Identification and functional characterization of p130Cas as a substrate of protein tyrosine phosphatase nonreceptor 14.
See PubMed abstract

Du Z, Song J, Wang Y, Zhao Y, Guda K, Yang S, Kao HY, Xu Y, Willis J, Markowitz SD, Sedwick D, Ewing RM, Wang Z (2010)
DNMT1 Stability Is Regulated by Proteins Coordinating Deubiquitination and Acetylation-Driven Ubiquitination.
Sci Signal;3(146):ra80
See PubMed abstract

Zhao Y, Zhang X, Guda K, Lawrence E, Sun Q, Watanabe T, Iwakura Y, Asano M, Wei L, Yang Z, Zheng W, Dawson D, Willis J, Markowitz SD, Satake M, Wang Z (2010)
Identification and functional characterization of paxillin as a target of protein tyrosine phosphatase receptor T.
Proc Natl Acad Sci U S A;:
See PubMed abstract

Zhang X, Guo C, Chen Y, Shulha HP, Schnetz MP, LaFramboise T, Bartels CF, Markowitz S, Weng Z, Scacheri PC, Wang Z (2008)
Epitope tagging of endogenous proteins for genome-wide ChIP-chip studies.
Nat Methods;5(2):163-5
See PubMed abstract

Zhang X, Guo A, Yu J, Possemato A, Chen Y, Zheng W, Polakiewicz RD, Kinzler KW, Vogelstein B, Velculescu VE, Wang ZJ (2007)
Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T.
Proc Natl Acad Sci U S A;104(10):4060-4
See PubMed abstract

Wang Z, Shen D, Parsons W, Bardelli A, Sager J, Szabo S, Ptak J, Silliman N, Peters BA, van der Heijden MS, Parmigiani G, Yan H, Wang TL, Riggins G, Powell S, M,James, Willson KV, Markowitz S, Kinzler KW, Vogelstein B, and Velculescu VE. (2004)
Mutational analysis of the tyrosine phosphatome in colorectal cancers.
See PubMed abstract

Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE. (2004)
High frequency of mutations of the PIK3CA gene in human cancers.
See PubMed abstract

Wang Z, Castano IB, De Las Penas A, Adams C, and Christman MF. (2000)
Pol kappa: A DNA polymerase required for sister chromatid cohesion
See PubMed abstract