Dr. Jianmin Zhang received his Ph.D. from the Department of Cellular Biochemistry & Human Genetics, Hadassah Medical School, Hebrew University of Jerusalem on 2004. He finished his postdoctoral training at the Cancer Center, Massachusetts General Hospital. In 2011, he joined Roswell Park Comprehensive Cancer Center as Assistant Member and Assistant Professor of Oncology.
Currently, he involves in Cellular and Molecular Biology Graduate Program and Genetics, Genomics and Bioinformatics Graduate Program of University at Buffalo.
Tumorigenesis in humans is a multi-step process, which reflects various genetic and epigenetic alterations. Tumor invasion and metastasis account for ~90% of all cancer deaths, and the process involves transitions between the epithelial and mesenchymal states (EMT and MET, which also occur during normal organ development). In particular, the EMT process has been implicated in promoting carcinoma invasion and metastasis. Initiation and progression of the EMT programming involves extensive crosstalk between various extracellular and intracellular signaling pathways, as well as regulatory components such as transcription factors (e.g., Twist, Snail1/2, Zeb1/2) and microRNAs (e.g., mir-200). However, the precise mechanisms of EMT are yet to be fully elucidated.
The Hippo signaling pathway is regarded as being critical in the regulation of organ size and tumorigenesis in both mammals and Drosophila. Dysregulation of Hippo pathway components, such as MST1/2, LATS1/2 and YAP, has been observed in human cancers, including hepatocellular carcinoma (HCC), oral squamous cell carcinoma, sarcomas, astrocytomas and breast cancer.
Using molecular, cellular and biochemical approaches as well as the 3-D cell culture system and mouse models, we are intensively investigating the roles of EMT and the Hippo signaling pathway in the initiation and progression of solid carcinomas, e.g., breast cancer.
The ultimate goal of my lab is to unravel the mechanisms of tumor development and metastasis, in the hope of revealing important new diagnostic and prognostic biomarkers, and more importantly, therapeutic strategies for the treatment of human cancer.
- Elucidation of the physiological regulation of the Hippo pathway and its dysregulation in cancer
- Study of mechanisms underlying the EMT in tumorigenesis and metastasis
- Epigenetic regulation of EMT and its cancer stem cell (CSC) properties
Li, YW, Shen, H, Frangou, C, Yang, N, Guo, J, Xu, B, Bshara, W, Shepherd, L, Zhu, Q, Wang, J, Hu, Q, Liu, S, Morrison, CD, Sun, P, Zhang J. Characterization of TAZ domains important for the induction of breast cancer stem cell properties and tumorigenesis. Cell cycle 2015; 14(1):146-56. PMID: 25602524
Frangou, C, Li, YW, Shen, H, Yang, N, Wilson, KE, Blijlevens, M, Guo, J, Nowak, NJ, Zhang J. Molecular profiling and computational network analysis of TAZ-mediated mammary tumorigenesis identifies actionable therapeutic targets. Oncotarget 2014 Dec 15; 5 (23):12166-76. PMID: 25361000
Wilson, KE, Li, YW, Yang, N, Shen, He, Orillion, AR, Zhang, J. PTPN14 forms complex with Kibra and LATS1 proteins and negatively regulates the YAP oncogenic function. The Journal of Biological Chemistry 2014; Aug 22; 289 (34): 23693-700 PMID: 25023289
Liu X, Yang N, Figel S, Wilson K, Morrison C, Gelman I, Zhang J. PTPN14 interacts with and negatively regulates the oncogenic function of YAP. Oncogene 2013; 32: 1266-1273. PMID: 22525271
Yang N., Morrison C.D., Liu P., Miecznikowski J., Bshara W., Han S., Zhu Q., Omilian A. R. Li X. and Zhang J. TAZ induces growth factor-independent proliferation through activation of EGFR ligand amphiregulin. Cell Cycle Aug 1; 11 (15): 2922-30, 2012
Zhang J, Ji J, Yu M, Overholtzer M, Smolen GA, Wang R, Brugge JS, Dyson NJ, Haber DA. YAP-dependent induction of amphiregulin identifies a non-cell autonomous component of the Hippo pathway. Nat Cell Biol 11(12): 1444-50, 2009
Zhang J, Smolen GA, Haber DA. Negative regulation of YAP by LATS1 underscores evolutionary conservation of the Drosophila Hippo pathway in mammals. Cancer Res 68(8): 2789-94, 2008
Shen H, Yang N, Truskinovsky A, Chen Y, Mussell AL, Nowak NJ, Kobzik L, Frangou C, Zhang J. Targeting TAZ-Driven Human Breast Cancer by Inhibiting a SKP2-p27 Signaling Axis. Mol Cancer Res. 2019 Jan;17(1):250-262. doi: 10.1158/1541-7786.MCR-18-0332. Epub 2018 Sep 20. PubMed PMID: 30237296; PubMed Central PMCID: PMC6318031.
Yang X, Shen H, Buckley B, Chen Y, Yang N, Mussell AL, Chernov M, Kobzik L, Frangou C, Han SX, Zhang J. NTRK1 is a positive regulator of YAP oncogenic function. Oncogene. 2019 Apr;38(15):2778-2787. doi: 10.1038/s41388-018-0609-1. Epub. 2018 Dec 12. PubMed PMID: 30542115.
Mussell AL, Denson KE, Shen H, Chen Y, Yang N, Frangou C, Zhang J. Loss of KIBRA function activates EGFR signaling by inducing AREG. Oncotarget,. 2018 Jul 6;9(52):29975-29984. doi: 10.18632/oncotarget.25724. eCollection 2018 Jul 6. PubMed PMID: 30042827; PubMed Central PMCID: PMC6057453.
Azad T, Janse van Rensburg HJ, Lightbody ED, Neveu B, Champagne A, Ghaffari A, Kay VR, Hao Y, Shen H, Yeung B, Croy BA, Guan KL, Pouliot F, Zhang J, Nicol CJB, Yang X. A LATS biosensor screen identifies VEGFR as a regulator of the Hippo pathway in angiogenesis. Nat Commun,. 2018 Mar 13;9(1):1061. doi: 10.1038/s41467-018-03278-w. PubMed PMID: 29535383; PubMed Central PMCID: PMC5849716.
Denson KE, Mussell AL, Shen H, Truskinovsky A, Yang N, Parashurama N, Chen Y, Frangou C, Yang F, Zhang J. The Hippo Signaling Transducer TAZ Regulates Mammary Gland Morphogenesis and Carcinogen-induced Mammary Tumorigenesis. Sci Rep. 2018 Apr 24;8(1):6449. doi: 10.1038/s41598-018-24712-5. PubMed PMID: 29691438; PubMed Central PMCID: PMC5915420.
Zhang Y, Shen H, Withers HG, Yang N, Denson KE, Mussell AL, Truskinovsky A, Fan Q, Gelman IH, Frangou C, Zhang J.VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer. Sci Rep. .2017 Jul 21;7(1):6190. doi: 10.1038/s41598-017-06227-7. PubMed PMID: 28733631; PubMed Central PMCID: PMC5522454.
Ciamporcero E, Shen H, Ramakrishnan S, Yu Ku S, Chintala S, Shen L, Adelaiye R, Miles KM, Ullio C, Pizzimenti S, Daga M, Azabdaftari G, Attwood K, Johnson C, Zhang J, Barrera G, Pili R. YAP activation protects urothelial cell carcinoma from treatment-induced DNA damage. Oncogene. 2016 Mar 24;35(12):1541-53. doi: 10.1038/onc.2015.219. Epub. 2015 Jun 29. PubMed PMID: 26119935; PubMed Central PMCID: PMC4695331.
Zhang J, Yao S, Hu Q, Zhu Q, Liu S, Lunetta KL, Haddad SA, Yang N, Shen H, Hong CC, Sucheston-Campbell L, Ruiz-Narvaez EA, Bensen JT, Troester MA, Bandera EV, Rosenberg L, Haiman CA, Olshan AF, Palmer JR, Ambrosone CB.Genetic variations in the Hippo signaling pathway and breast cancer risk in African American women in the AMBER Consortium. Carcinogenesis. 2016 Oct;37(10):951-956. doi: 10.1093/carcin/bgw077. Epub 2016 Aug 1. PubMed PMID: 27485598; PubMed Central PMCID: PMC5035397.