Bin Zheng Ph.D.
Cutaneous Biology Research Center
Massachusetts General Hospital
Harvard Medical School
Building 149, 13th Street, Room 3217
Charlestown, MA 02129
Tel: 617-724-9958 Fax: 617-726-4453
The focus of our laboratory research is metabolic signaling in melanoma. We are interested in understanding how rewired metabolism in cancer cells is coordinated with other hallmarks of cancer to influence caner initiation, promotion and progression. Approximately half of all melanomas harbor an activating mutation in BRAF (BRAFV600E) that drives cancer growth due to the constitutive activation of the downstream MEK/ERK pathway. The “addiction” of melanomas harboring this BRAF mutation has stimulated the development of BRAF inhibitors (BRAFi), such as Vemurafenib and Dabrafenib. These BRAFi have shown great clinical benefits in malignant melanoma with BRAFV600E mutations in the initial phase of treatment. However, the vast majority of the responsive melanoma patients treated with BRAF inhibitors develop resistance during the course of treatment and relapsed. In addition to the BRAF-targeted therapy, another recent major groundbreaking approach in melanoma treatment is to target the immune checkpoints that exploit melanoma’s intrinsically high immunogenicity. Biological drugs that target CTLA-4, PD-1 or PD-L1 have shown significant clinical benefits in melanoma patients with a high degree of durable responses, but only in a subset of patients. Therefore, improving the response rates of immunotherapies and overcoming BRAFi resistance represent two of the greatest challenges facing this field. The overarching goal of our research is to address this by gaining a better understanding of metabolic programming in melanoma and to translate these basic research findings into better strategies for melanoma prevention, diagnosis and treatment. In particular, we currently focus on the following areas of research:
1) BRAF-dependent metabolic wiring and rewiring;
2) Metabolic heterogeneity in cancer;.
3)Metabolic regulation of tumor immunity;
|4)Roles of AMPK at the interface of metabolism and Cancer;|
|5)Reviving Phenformin for Cancer Therapy.|
Bin Zheng Ph.D.
Ph.D. Molecular Pathology, University of California, San Diego 2002
Beth Israel Deaconess Medical Center, Harvard Medical School. Signal Transduction / Cancer Biology. 2008
University of California, San Diego. Cell Biology. 2003
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
Sebastian Trousil and Bin Zheng. 2015. Addicted to AA (Acetoacetate): A Point of Convergence between Metabolism and BRAF Signaling. Mol. Cell. 59(3), 333-334.
Bin Zheng and David Fisher. 2015. Metabolic Vulnerability in Melanoma: A ME2 (Me Too) Story. J. Inv. Derm. 135, 657–659.
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.
Public Transportation Access: yes
Disabled Access: yes
Directions to Charlestown Navy Yard MGH East - Building 149
From Storrow Drive
From 93 North
- 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 South
- 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.
- 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 Public Transportation & the MGH/Partners Shuttle
- Direct the driver to the MGH East, Building 149 in the Charlestown Navy Yard.
- The CBRC is on the 3rd Floor of Building 149.
- 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).
- 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.