Photo of Bin Zheng,  PhD

Bin Zheng, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 724-9958

Bin Zheng, PhD

Massachusetts General Hospital


  • Associate Professor, Dermatology, Harvard Medical School
  • Assistant Biologist, Dermatology, Massachusetts General Hospital


Research Abstract

The focus of our laboratory research is on metabolic signaling in melanoma. We are interested in understanding how rewired metabolism in cancer cells is coordinated with other hallmarks of cancer to influence cancer 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. Preclinical work from his laboratory on AMPK and phenformin have led to a Phase I clinical trial evaluating phenformin with the dabrafenib BRAF inhibitor and trametinib MEK inhibitor combination in patients with BRAF mutant melanoma.

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.


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  • Zhao H, Zheng B. Dual Targeting of Autophagy and MEK in KRAS Mutant Cancer. Trends Cancer 2019; 5:327-329. PubMed
  • Li S, Lavagnino Z, Lemacon D, Kong L, Ustione A, Ng X, Zhang Y, Wang Y, Zheng B, Piwnica-Worms H, Vindigni A, Piston DW, You Z. Ca-Stimulated AMPK-Dependent Phosphorylation of Exo1 Protects Stressed Replication Forks from Aberrant Resection. Mol Cell 2019. PubMed
  • Chen S, Zhuang K, Sun K, Yang Q, Ran X, Xu X, Mu C, Zheng B, Lu Y, Zeng J, Dai Y, Sushmita P, Ran Y. Itraconazole induces regression of infantile hemangioma via down-regulation of the PDGF-D/PI3K/Akt/mTOR pathway. J Invest Dermatol 2019. PubMed
  • Strub T, Ghiraldini FG, Carcamo S, Li M, Wroblewska A, Singh R, Goldberg MS, Hasson D, Wang Z, Gallagher SJ, Hersey P, Ma'ayan A, Long GV, Scolyer RA, Brown B, Zheng B, Bernstein E. SIRT6 haploinsufficiency induces BRAF melanoma cell resistance to MAPK inhibitors via IGF signalling. Nat Commun 2018; 9:3440. PubMed
  • Swanson KD, Zheng B. Supplementing Cancer? Mol Cell 2018; 69:917-918. PubMed
  • Kim SH, Li M, Trousil S, Zhang Y, Pasca di Magliano M, Swanson KD, Zheng B. Phenformin Inhibits Myeloid-Derived Suppressor Cells and Enhances the Anti-Tumor Activity of PD-1 Blockade in Melanoma. J Invest Dermatol 2017. PubMed
  • Casimiro MC, Di Sante G, Di Rocco A, Loro E, Pupo C, Pestell TG, Bisetto S, Velasco-Velázquez MA, Jiao X, Li Z, Kusminski CM, Seifert EL, Wang C, Ly D, Zheng B, Shen CH, Scherer PE, Pestell RG. Cyclin D1 Restrains Oncogene-Induced Autophagy by Regulating the AMPK-LKB1 Signaling Axis. Cancer Res 2017; 77:3391-3405. PubMed
  • Waldhart AN, Dykstra H, Peck AS, Boguslawski EA, Madaj ZB, Wen J, Veldkamp K, Hollowell M, Zheng B, Cantley LC, McGraw TE, Wu N. Phosphorylation of TXNIP by AKT Mediates Acute Influx of Glucose in Response to Insulin. Cell Rep 2017; 19:2005-2013. PubMed
  • Trousil S, Chen S, Mu C, Shaw FM, Yao Z, Ran Y, Shakuntala T, Merghoub T, Manstein D, Rosen N, Cantley LC, Zippin JH, Zheng B. Phenformin enhances the efficacy of ERK inhibition in NF1-mutant melanoma. J Invest Dermatol 2017. PubMed
  • Wu L, Zhou B, Oshiro-Rapley N, Li M, Paulo JA, Webster CM, Mou F, Kacergis MC, Talkowski ME, Carr CE, Gygi SP, Zheng B, Soukas AA. An Ancient, Unified Mechanism for Metformin Growth Inhibition in C. elegans and Cancer. Cell 2016; 167:1705-1718.e13. PubMed
  • Shen CH, Kim SH, Trousil S, Frederick DT, Piris A, Yuan P, Cai L, Gu L, Li M, Lee JH, Mitra D, Fisher DE, Sullivan RJ, Flaherty KT, Zheng B. Loss of cohesin complex components STAG2 or STAG3 confers resistance to BRAF inhibition in melanoma. Nat Med 2016. PubMed
  • Trousil S, Zheng B. Addicted to AA (Acetoacetate): A Point of Convergence between Metabolism and BRAF Signaling. Mol Cell 2015; 59:333-4. PubMed
  • Zheng B, Fisher DE. Metabolic vulnerability in melanoma: a ME2 (me too) story. J Invest Dermatol 2015; 135:657-9. PubMed
  • DeRan M, Yang J, Shen CH, Peters EC, Fitamant J, Chan P, Hsieh M, Zhu S, Asara JM, Zheng B, Bardeesy N, Liu J, Wu X. Energy stress regulates hippo-YAP signaling involving AMPK-mediated regulation of angiomotin-like 1 protein. Cell Rep 2014; 9:495-503. PubMed
  • Yuan P, Ito K, Perez-Lorenzo R, Del Guzzo C, Lee JH, Shen CH, Bosenberg MW, McMahon M, Cantley LC, Zheng B. Phenformin enhances the therapeutic benefit of BRAF(V600E) inhibition in melanoma. Proc Natl Acad Sci U S A 2013. PubMed
  • Shen CH, Yuan P, Perez-Lorenzo R, Zhang Y, Lee SX, Ou Y, Asara JM, Cantley LC, Zheng B. Phosphorylation of BRAF by AMPK impairs BRAF-KSR1 association and cell proliferation. Mol Cell 2013. PubMed
  • Wu N, Zheng B, Shaywitz A, Dagon Y, Tower C, Bellinger G, Shen CH, Wen J, Asara J, McGraw TE, Kahn BB, Cantley LC. AMPK-dependent degradation of TXNIP upon energy stress leads to enhanced glucose uptake via GLUT1. Mol Cell 2013; 49:1167-75. PubMed
  • Mack HI, Zheng B, Asara JM, Thomas SM. AMPK-dependent phosphorylation of ULK1 regulates ATG9 localization. Autophagy 2012; 8:1197-214. PubMed
  • Dagon Y, Hur E, Zheng B, Wellenstein K, Cantley LC, Kahn BB. p70S6 kinase phosphorylates AMPK on serine 491 to mediate leptin's effect on food intake. Cell Metab 2012; 16:104-12. PubMed
  • Tsou P, Zheng B, Hsu CH, Sasaki AT, Cantley LC. A fluorescent reporter of AMPK activity and cellular energy stress. Cell Metab 2011; 13:476-86. PubMed
  • 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. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab 2011; 13:376-88. PubMed
  • Zheng B,Jeong JH,Asara JM,Yuan YY,Granter SR,Chin L,Cantley LC. Oncogenic B-RAF negatively regulates the tumor suppressor LKB1 to promote melanoma cell proliferation. Mol Cell 2009; 33:237-47. PubMed