Cutaneous Biology Research Center

photo

Bin Zheng, Ph.D

Our lab studies metabolic signaling in skin diseases, particular in melanoma.

Bin Zheng Ph.D.
Cutaneous Biology Research Center

Massachusetts General Hospital

Harvard Medical School

Building 149, 13th Street, Room 3217

Charlestown, MA 02129

Email: bin.zheng@cbrc2.mgh.harvard.edu
Tel:  617-724-9958        Fax: 617-726-4453

Research Summary

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 thatserves 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 therapeuticpotential 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.

 Bin Zheng Ph.D.

Education

Ph.D. Molecular Pathology, University of California, San Diego 2002

Postdoctoral Training

Beth Israel Deaconess Medical Center, Harvard Medical School. Signal Transduction / Cancer Biology. 2008

University of California, San Diego. Cell Biology. 2003

Honors

1997-2000  Huang Memorial Scholarship, University of California San Diego

2002-2003 Postdoctoral Fellowship, American Heart Association

2005-2007  Charles King Trust Postdoctoral Fellowship

2008  AACR Scholar-in-training Award

2008-2013  The Pathway to Independence Award (K99/R00), NIH/NCI

2010  Keystone Symposia Scholarship

2011-2014  Elizabeth and Oliver Stanton - MRA (Melanoma Research Alliance) Young Investigator Award

2011  Alexander and Margaret Stewart Trust Pilot Project Award

2011  V Scholar, The V Foundation for Cancer Research

 2013   Irma T. Hirschl Trust Career Scientist Award

Selected publications

Che-Hung Shen, Rolando Perez-Lorenzo, Ping Yuan, Yang Ou, Sze Xian Lee, John Asara, Lewis C. Cantley and Bin Zheng. 2013. AMPK phosphorylates BRAF to regulate BRAF-KSR1 association and cell proliferation. Molecular Cell.  52:161-172

Ping Yuan, Koichi Ito, Rolando Perez-Lorenzo, Christina Del Guzzo, Jung Hyun Lee, Che-Hung Shen, Marcus W. Bosenberg, Martin McMahon, Lewis C. Cantley, Bin Zheng. 2013 Phenformin enhances the therapeutic benefit of BRAFV600E inhibition in melanoma. Proc. Natl. Acad. Sci. USA  110(45). www.pnas.org/cgi/doi/10.1073/pnas.1317577110

Ning Wu, Bin Zheng, Adam Shaywitz, Yossi Dagon, Christine Tower, Gary Bellinger, Che-Hung Shen, John Asara, Barbara Kahn, Lewis C. Cantley. AMPK-dependent degradation of TXNIP in response to energy stress results in enhanced glucose uptake via GLUT1. Molecular Cell 49:1167-75.

Dagon, Y., E. Hur, B. Zheng, K. Wellenstein, L.C. Cantley, and B. B. Kahn. 2012. p70S6-kinase phosphorylates AMPK on serine 491 to mediate leptin’s effect on food intake. Cell Metab. 16(1):104-112.

Tsou, P., B. Zheng, C.H. Hsu, A.T. Sasaki, and L.C. Cantley. 2011. A fluorescent reporter of AMPK activity and cellular energy stress. Cell Metab. 13:476-86.

Amato, S., X. Liu, B. Zheng, L. Cantley, P. Rakic, and H.Y. Man. 2011. AMP-activated protein kinase regulates neuronal polarization by interfering with PI 3-kinase localization. Science. 332:247-51.

Li, Y., S. Xu, M.M. Mihaylova, B. Zheng, X. Hou, B. Jiang, O. Park, Z. Luo, E. Lefai, J.Y. Shyy, B. Gao, M. Wierzbicki, T.J. Verbeuren, R.J. Shaw, R.A. Cohen, and M. Zang. 2011. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 13:376-88.

Zheng, B., Jeong, J.H., Asara, J.M., Yuan, Y., Granter, S.R., Chin, L. & Cantley, L.C. Oncogenic B-RAF Negatively Regulates the Tumor Suppressor LKB1 to Promote Melanoma Cell Proliferation. Molecular Cell 33, 237-247 (2009)

Tang, T., Zheng, B., Chen, S., Murphy, A.N., Kudlicka, K., Zhou, H. & Farquhar, M.G. hNOA1 Interacts With Complex I and DAP3 and Regulates Mitochondrial Respiration and Apoptosis. J Biol Chem 284:5414-24 (2009).

Zheng, B., and L.C. Cantley. 2007. Regulation of epithelial tight junction assembly and disassembly by AMP-activated protein kinase. Proc. Natl. Acad. Sci. USA 104:8-11.

Asara, J.M., Zhang, X., Zheng, B., Maroney, L.A., Christofk, H.H., Wu, N., and L.C. Cantley. 2006. In-Gel Stable Isotope Labeling for relative quantification using mass spectrometry. Nature Protocols. 1:46-51.

Zheng, B., Tang, T., Tang, N., Kudlicka, K., Ohtsubo, K., Ma, P., Marth, J.D., Farquhar, M.G., and E. Lehtonen.  2006. Essential role of RGS-PX1/sorting nexin 13 in mouse development and regulation of endocytosis dynamics.  Proc. Natl. Acad. Sci. USA 103: 16776-81.

Zheng, B., Lavoie, C., Tang, T.D., Ma, P., Meerloo, T., Beas, A., and M. G. Farquhar 2004.  Regulation of EGF Receptor Degradation by Heterotrimeric  G-alpha-s Protein. Mol. Biol. Cell. 15:5538-5550.

Zheng, B., Berrie, C., Corda, D. and M. G. Farquhar. 2003.  GDE1/MIR16 is a Glycerophosphoinositol Phosphodiesterase Regulated by Stimulation of G Protein-Coupled Receptors.  Proc. Natl. Acad. Sci. USA 100:1745-1750.

Zheng, B., Ma, Y-C, Ostrom, R.S., Lavoie, C., Gill, G., Insel, P.A., Huang, X-Y, and M. G. Farquhar, 2001.  RGS-PX1, GAP for G-alpha-s and a sorting nexin in vesicular trafficking.  Science 294:1939-1942.

Zheng, B., Chen, D. and M.G. Farquhar  2000.  MIR16, a putative membrane glycerophosphodiester phosphodiesterase, interacts with RGS16.  Proc. Natl. Acad. Sci. USA 97:3999-4004.

De Vries, L., Zheng, B., Fischer, T., Elenko, E., and M. G.  Farquhar  2000. The Regulator of G Protein Signaling (RGS) family.   Annu. Rev. Pharmacol. & Toxicol. 40:235-271.

Zheng, B., De Vries, L., and M. G. Farquhar.  1999.  Divergence of RGS proteins: Evidence for the existence of six mammalian RGS subfamilies. Trends Biochem. Sci.  24:411-414.

Bin Zheng, Ph.D

Cutaneous Biology Research Center
Massachusetts General Hospital
Building 149 , 13th Street. Room 3217
Charlestown, MA 02129

Phone: 617-724-9958
Fax: 617-726-4453
Email: bin.zheng@cbrc2.mgh.harvard.edu

Public Transportation Access: yes
Disabled Access: yes

Directions to Charlestown Navy Yard MGH East - Building 149

From Storrow Drive

  • From the end of Storrow Drive (Leverett Circle) keep to the far right and take a sharp right (do not go up the ramp), and continue beneath the underpass one quarter mile to the light.
  • Turn left onto Causeway street under the elevated subway tracks. The Fleet Center will be on your left, the North Station T station on your right.
  • One block past the Garden, turn left on to N. Washington Street, passing over the Charlestown Bridge. 
  • At the first light after the bridge, take a right. Go through three traffic control lights. 
  • At the fourth light, turn right into Navy Yard (Gate 5 - 13th Street). To park, take first left onto Fifth Avenue. Building 149 is one block on the right.
  • The parking garage entrance is on the right about half way down the block.
From 93 North
  • Take the Mass Pike (I-90) to I-93 North (Exit 24B)
  • Take the Storrow Drive Exit (Exit 26)Stay in the left lane once getting on the exit ramp. Follow signs for North Station/Leverett Circle Go through 1 light and take left at the 2nd light (almost immediately after the first)
  • Get immediately into the right lane 
  • Take a right at the light onto Route 28N 
  • The Museum of Science will be on your left 
  • Take a right at the 3rd light (there is a sign at the corner for Charlestown) 
  • Go over the bridge and get in the right lane (City Square)
  • Take your 1st right and get into the left lane 
  • Turn left at the 2nd light (immediately before Charlestown Bridge, at City Square) onto Chelsea Street (If you go over bridge, you've gone too far). 
  • Go through three traffic control lights
  • At the 4th light, turn right into the Navy Yard (Gate 5 - 13th Street).
  • To park, take first left onto Fifth Avenue. Parking Garage entrance is on the right above half way down the block. Building 149 is one block on the right once you turn into Gate 5. Building 149 is also connected to the parking garage.
From 93 South
  • Take Exit 28 (Charlestown/Sullivan Square).
  • At the end of the exit where the read forks stay to the right and proceed past the bus terminal to the rotary at Sullivan Square.
  • Go halfway around the rotary towards Charlestown (the Schrafts building with a large American flag on top of it will be on your left).
  • Cross the railroad tracks and take a left at the fire station onto Medford Street.
  • At the end of Medford street turn left onto Chelsea Street and make an immediate right into the Navy Yard.
  • The MGH East Research Building (Bldg. 149) will be on the right and is connected to the parking garage by overhead walkways.
By Taxi
  • Direct the driver to the MGH East, Building 149 in the Charlestown Navy Yard.
  • The CBRC is on the 3rd Floor of Building 149.
By Public Transportation & the MGH/Partners Shuttle
  • Take the T (Green Line) to North Station
  • Take the MGH/Partners Shuttle bus to the Charlestown Navy Yard MGH East Research Building (Building 149). 
  • The CBRC is on the 3rd Floor.
  • The MGH/Partners Shuttle bus leaves MGH on Blossom Street and stops at North Station on Canal Street by the Green Line T stop. The shuttle goes every 15 minutes during working hours. (Less often on the weekends and holidays).
The CBRC
  • To get to the CBRC, take the first set of elevators to the left of the main entrance by the Security Desk to the third floor. You may need to check in with security on the main level of Building 149.
  • From the elevator, exit to the East to the CBRC offices, or in the opposite direction for the laboratories.