Zheng lab
Massachusetts General Hospital
Field(s) of Research: Cancer, Signal Transduction
Disease Focus: Melanoma, Skin Cancer
Website: http://www.lablife.org/labs/2770
LabLife URL: http://www.lablife.org/labs/2770
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Contact Us
Email: bin.zheng@cbrc2.mgh.harvard.edu
Phone: 617-724-9958
Fax: 617-726-4453
Building 149, 13th Street, Room 3217
Charlestown, MA 02129
United States
Lab Members
Cancer Cell Metabolism
Our laboratory is interested in deciphering the molecular mechanisms of metabolic signaling in cancer, with special emphasis on melanoma, and translating these basic research findings into potential personalized targeted therapies. The focus of our current research is on the LKB1-AMPK signaling pathway, which couples energy metabolism to cell growth, proliferation and survival. AMPK (AMP-activated protein kinase) is a Ser/Thr protein kinase that serves as a cellular energy sensor. The activity of AMPK is regulated by the AMP/ATP ratio and by upstream activating kinases, including the tumor suppressor LKB1. Metformin, one of the most prescribed drugs for treating type II diabetes, has been shown to target the LKB1-AMPK pathway and is currently being evaluated for the treatment of cancer in clinical trials. Understanding the complex LKB1-AMPK signaling circuitries underlying tumorigenesis will contribute to the development of effective therapeutic strategies.

Our current research directions include:

1) Identification of novel substrates of AMPK and characterization of their roles in cancer biology. We are using a combination of bioinformatics, proteomics and metabolomics approaches to uncover critical AMPK substrates relevant to cancer biology, especially those involved in cancer cell metabolism and EMT (Epithelial Mesenchymal Transition).

2) Down-regulation of LKB1 and AMPK in Cancer. The LKB1-AMPK pathway serves as an "energy brake" to suppress cell growth and proliferation under energy stress conditions. Cancer cells need to inactivate this pathway in order to gain a growth advantage over normal cells. We are studying various mechanisms by which the LKB1-AMPK "energy brake" is "overridden" in cancer.

3) Cross-talk between LKB1-AMPK and RAF-MEK-ERK signaling pathways. RAF signaling pathway is one of the other most important signaling pathways in cancer. We have recently discovered that this pathway is tightly linked to the LKB1-AMPK pathway. Currently we are continuing to investigate the biochemical mechanism by which these two pathways interact and regulate each other’s functions. Moreover, we are assessing the therapeutic potential of combining drugs targeting both of these pathways (metformin and RAF/MEK inhibitors) in melanoma treatment using various preclinical models, such as xenograft and genetically engineered mouse models.

Our projects are supported by:
-- National Cancer Institute (http://www.cancer.gov/)
-- Elizabeth and Oliver Stanton MRA Young Investigator Award from Melanoma Research Alliance (http://www.melanomaresearchalliance.org/)
-- The V Foundation (http://www.jimmyv.org/)
-- The Alexander and Margaret Stewart Trust (http://www.stewart-trust.org/)
-- The Irma T. Hirschl Trust Career Scientist Award

Other Websites:



Yuan P, Ito K, Perez-Lorenzo R, Del Guzzo C, Lee JH, Shen CH, Bosenberg MW, McMahon M, Cantley LC, Zheng B
Proc Natl Acad Sci U S A. 2013 Oct 21. ():.
Shen CH, Yuan P, Perez-Lorenzo R, Zhang Y, Lee SX, Ou Y, Asara JM, Cantley LC, Zheng B
Mol Cell. 2013 Oct 1. ():.
Wu N, Zheng B, Shaywitz A, Dagon Y, Tower C, Bellinger G, Shen CH , Wen J, Asara J, McGraw TE, Kahn BB, Cantley LC
Mol Cell. 2013 Feb 26. ():.
Mack HI, Zheng B, Asara J, Thomas SM
Autophagy. 2012 Aug 1. 8(8):.
Yang Y, Wu J, Demir A, Castillo-Martin M, Melamed RD, Zhang G, Fukunaga-Kanabis M, Perez-Lorenzo R, Zheng B, Silvers DN, Brunner G, Wang S, Rabadan R, Cordon-Cardo C, Celebi JT
Oncogene. 2012 Aug 27. ():.
Dagon Y, Hur E, Zheng B, Wellenstein K, Cantley LC, Kahn BB
Cell Metab. 2012 Jun 21. ():.
Pérez-Lorenzo R , Zheng B
Biosci Rep. 2012 Feb 1. 32(1):25-33.
Tsou P, Zheng B, Hsu CH, Sasaki AT, Cantley LC
Cell Metab. 2011 Apr 6. 13(4):476-86.
Li Y, Xu S, Mihaylova MM, Zheng B, Hou X, Jiang B, Park O, Luo Z, Lefai E, Shyy JY, Gao B, Wierzbicki M, Verbeuren TJ, Shaw RJ, Cohen RA, Zang M
Cell Metab. 2011 Apr 6. 13(4):376-88.
Amato S, Liu X, Zheng B, Cantley L, Rakic P, Man HY
Science. 2011 Mar 24. ():.
Zheng B, Jeong JH, Asara JM, Yuan YY, Granter SR, Chin L, Cantley LC
Mol Cell. 2009 Jan 30. 33(2):237-47.
Asara JM, Zhang X, Zheng B, Maroney LA, Christofk HR, Wu N, Cantley LC
Nat Protoc. 2006 . 1(1):46-51.
Zheng B, Cantley LC
Proc Natl Acad Sci U S A. 2007 Jan 16. 104(3):819-22.