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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
E-mail: zhenghe.wang@case.edu


About Zhenghe Wang

John Wang received his Ph.D. in Microbiology from University of Virginia in 2001. He was a postdoctoral fellow with Dr. Bert Vogelstein in the Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins University. Dr. Wang joined the Department of Genetics and the Case Comprehensive Cancer Center in August, 2005. He has been co-leader of the GI cancer genetics program at Case Comprehensive Cancer Center since 2014. He was named as a co-leader of the Standup to Cancer (SU2C) Colorectal Cancer Dream Team in 2017.


Research

Dr. Wang's research program focuses on defining mechanisms of oncogenesis at the molecular, regulatory and phenotypic levels and translating these discoveries to new cancer therapies.

Dr. Wang co-discovered that PIK3CA, which encodes p110a catalytic subunit of PI3 kinase, is frequently mutated in human cancers. His laboratory recently found that PIK3CA mutations render colorectal cancer dependent on glutamine. He has successfully translated these discoveries into ongoing phase I/II clinical trials. This line of research is currently funded by a SU2C colorectal cancer Dream Team award, the Case GI SPORE and an RO1 from the National Cancer Institute.

Dr. Wang also is interested in defining the roles of pseudo-kinases and pseudo-phosphatases in tumorigenesis. The human genome encodes 48 pseudo-kinases and 17 pseudo-phosphatases, which are thought to be enzymatically inactive. However, his laboratory recently discovered that the pseudo-phosphatase domain of protein tyrosine phosphatase receptor T (PTPRT) is in fact an active enzyme which removes nitration (NO2) from tyrosine residues in proteins. His lab has demonstrated that this denitrase functions as a tumor suppressor (https://www.biorxiv.org/content/early/2017/12/22/238980).


Selected Publications

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

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

Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancer.
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
Nat Commun (2016);7:11971
See PubMed abstract

Genetic alterations of protein tyrosine phosphatases in human cancers.
Zhao S, Sedwick D, Wang Z
Oncogene (2015);34(30):3885-94
See PubMed abstract

TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration.
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
Science (2015);348(6240):aaa2340
See PubMed abstract

Novel recurrently mutated genes in African American colon cancers.
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
Proc Natl Acad Sci U S A (2015);112(4):1149-54
See PubMed abstract

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

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

DNMT1 Stability Is Regulated by Proteins Coordinating Deubiquitination and Acetylation-Driven Ubiquitination.
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
Sci Signal (2010);3(146):ra80
See PubMed abstract

Identification and functional characterization of paxillin as a target of protein tyrosine phosphatase receptor T.
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
Proc Natl Acad Sci U S A (2010);:
See PubMed abstract

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

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

Mutational analysis of the tyrosine phosphatome in colorectal cancers.
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.
Science (2004);304(5674):1164-6
See PubMed abstract

High frequency of mutations of the PIK3CA gene in human cancers.
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.
Science (2004);304(5670):554
See PubMed abstract