Binfeng Lu, PhD
Campus: 200 Lothrop St
Office: E1047 BSTWR
Pittsburgh, PA 15261
- Ph.D. - Columbia University (1998)
- Postdoc - Yale University (1998-2003)
- B.S. - Tsinghua University, Beijing (1992)
- Associate Professor
- Member, University of Pittsburgh Cancer Institute
The lab is interested in using data science for the discovery of novel molecular and cellular pathways regulating key steps of T cell-mediated tissue-focused immune responses in antitumor immunity and autoimmunity. Such studies have helped identifying key therapeutic targets in the immune oncology field.
Discovery of novel targets in tumor associated immune cells for improving T cell-mediated immunotherapy of cancer.
Our basic research is driven by biological Data science aiming at constructing and understanding the cellular and molecular immune networks in the tumor tissues. We are discovering new targets for immunotherapy of cancer through studying the molecular basis underlying effective antitumor T cell immune responses in human cancer.
We have found that the IL-33 receptor is up-regulated in effector Th1 and CD8 T cells. We further established that expression of IL-33 in tumor cells greatly inhibited tumor growth through enhancing the function of CD8 T cells and NK cells and inhibiting MDSC within tumor. Current interest is to explore IL-33 in immunotherapy of cancer and Mode of action by IL-33 class drugs in immune oncology.
Besides positive regulators of antitumor immune responses, we also have keen interest in understanding what are the “brakes” that limit an otherwise successful cancer immunotherapy. Our past work has identified several molecules that have such functions. We discovered that one such “immune brake” TIM-3 is highly expressed in tumor-infiltrating T cells in both human and mouse tumors. Blockade of TIM-3 should significantly improve immunotherapy of cancer. In close collaboration with clinicians and the biotech industry, we are actively involved in translating these new findings to the clinical setting, which should greatly benefit cancer patients.
Adaptive metabolic programing in T cells in autoimmunity and cancer immunity.
Our focus is on two major metabolic regulatory pathways namely Autophagy and the Integrated Stress Response pathway. Our studies have helped establish that these pathways are a critical intracellular process regulating T cell signaling, metabolism, clonal expansion and fate decision. Mechanistic studies of Beclin 1/Atg6 in autophagy and ATF4 in regulating amino acid metabolic reprogramming in T cells generate new insights to T cell Biology and immune related diseases.
Liu Z, McMichael EL, Shayan G, Li J, Chen K, Srivastava RM, Kane LP, Lu B, Ferris RL. Novel effector phenotype of Tim-3+ regulatory T cells leads to enhanced suppressive function in head and neck cancer patients. Clin Cancer Res. 2018 Apr 30.
Yang M, Feng Y, Yue C, Xu B, Chen L, Jiang J, Lu B*, Zhu Y*. Lower expression level of IL-33 is associated with poor prognosis of pulmonary adenocarcinoma. PLoS One. 2018 Mar 2;13(3):e0193428.*co-corresponding authors.
Chen Y, Xia R, Huang Y, Zhao W, Li J, Zhang X, Wang P, Venkataramanan R, Fan J, Xie W, Ma X, Lu B, Li S. An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy. Nat Commun. 2016 Nov 7;7:13443.
Shi L, Chen L, Wu C*, Zhu Y, Xu B, Zheng X, Sun M, Wen W, Dai X, Yang M, Lv Q, Lu B*, Jiang J* PD-1 blockade boosts radiofrequency ablation-elicited adaptive immune responses against tumor. Clinical Cancer Research 2015 (In press) * corresponding authors.
Wang X, Zhao X, Feng C, Weinstein A, Xia R, Wen W, Lv Q, Zuo S, Tang P, Yang X, Chen X, Wang H, Zang S, Stollings L, Denning TL, Jiang J, Fan J, Zhang G, Zhang X, Zhu Y, Storkus W, Lu B. IL-36γ Transforms the Tumor Microenvironment and Promotes Type 1 Lymphocyte-Mediated Antitumor Immune Responses. Cancer Cell. 2015 Aug 26. pii: S1535-6108(15)00266-4. doi: 10.1016/j.ccell.2015.07.014.
Gao X, Wang X, Yang Q, Zhao X, Wen W, Li G, Lu J, Qin W, Qi Y, Xie F, Jiang J, Wu C, Zhang X, Chen X, Turnquist H, Zhu Y, Lu B. Tumoral Expression of IL-33 Inhibits Tumor Growth and Modifies the Tumor Microenvironment through CD8+T and NK Cells. J Immunol. 2014 Nov 26.
Li G, Yang Q, Zhu Y, Wang HR, Chen X, Zhang X, Lu B. T-Bet and Eomes Regulate the Balance between the Effector/Central Memory T Cells versus Memory Stem Like T Cells. PLoS One. 2013 Jun 27;8(6):e67401.
Tang Y, Xu X, Guo S, Zhang C, Tang Y, Tian Y, Ni B*, Lu B*, Wang H*, An increased abundance of tumor-infiltrating regulatory T cells is correlated with the progression and prognosis of pancreatic ductal adenocarcinoma. PLoS One. 2014 Mar 17;9(3):e91551. doi: 10.1371/journal.pone.0091551. eCollection 2014. *co-corresponding authors.
Zeng T, Wang Q, Fu J, Lin Q, Bi J, Ding W, Qiao Y, Zhang S, Zhao W, Lin H, Wang M, Lu B, Deng X, Zhou D, Yin Z, Wang HR. Impeded Nedd4-1-mediated Ras degradation underlies Ras-driven tumorigenesis. Cell Rep. 2014 May 8;7(3):871-82.
Zhang L, Wu H, Lu D, Li G, Sun C, Song H, Li J, Zhai T, Huang L, Hou C, Wang W, Zhou B, Chen S, Lu B, Zhang X. The costimulatory molecule B7-H4 promote tumor progression and cell proliferation through translocating into nucleus. Oncogene. 2013 Nov 14;32(46):5347-58.
Chen LJ, Zheng X, Shen YP, Zhu YB, Li Q, Chen J, Xia R, Zhou SM, Wu CP, Zhang XG, Lu BF*, Jiang JT*. Higher numbers of T-bet(+) intratumoral lymphoid cells correlate with better survival in gastric cancer. Cancer Immunol Immunother. 2013 Mar;62(3):553-61.*co-corresponding authors.
Gao X, Zhu Y, Li G, Huang H, Zhang G, Wang F, Sun J, Yang Q, Zhang X, Lu B. TIM-3 expression characterizes regulatory T cells in tumor tissues and is
associated with lung cancer progression. PLoS One. 2012;7(2):e30676. doi: 10.1371/journal.pone.0030676.
Yang Q, Li G, Zhu Y, Liu L, Chen E, Turnquist H, Zhang X, Finn OJ, Chen X, Lu B. IL-33 synergizes with TCR and IL-12 signaling to promote the effector function of CD8(+) T cells. Eur J Immunol. 2011 Sep 2.
Chen LJ, Sun J, Wu HY, Zhou SM, Tan Y, Tan M, Shan BE, Lu BF*, Zhang XG*. B7-H4 expression associates with cancer progression and predicts patient's survival in human esophageal squamous cell carcinoma. Cancer Immunol Immunother. 2011 Jul;60(7):1047-55. *co-corresponding authors
Jiang J, Zhu Y, Wu C, Shen Y, Wei W, Chen L, Zheng X, Sun J, Lu B*, and Zhang X*, Tumor Expression of B7-H4 predicts poor Survival of Patients Suffering from Gastric Cancer. Cancer Immunology Immunotherapy 2010 Aug 20. *corresponding author.
Zhu Y, Ju S, Chen E, Dai S, Li C, Morel P, Liu L, Zhang X, Lu B. T-bet and Eomesodermin Are Required for T Cell-Mediated Antitumor Immune Responses. J Immunol. 2010 Aug 16.
Adaptive metabolic programing in T cells
Yang X, Xia R, Yue C, Zhai W, Du W, Yang Q, Cao H, Chen X, Obando D, Zhu Y, Chen X, Chen JJ, Piganelli J, Wipf P, Jiang Y, Xiao G, Wu C, Jiang J, Lu B. ATF4 Regulates CD4(+) T Cell Immune Responses through Metabolic Reprogramming. Cell Rep. 2018 May 8;23(6):1754-1766.
Kovacs J, Yang Q, Gonzalez-García I, Li C, Ju S, Gonzales-Garcia I, Chen X, Zhang X, and Lu B, Autophagy promotes T cell survival through degradation of proteins of the cell death machinery. Cell Death and Differentiation 2011 Jun 10.
Li C, Capan E, Zhao Y, Zhao J, Stolz D, Watkins S, Jin S, Lu B. Autophagy is induced in CD4+ T cells and important for the growth factor-withdrawal cell death. The Journal of Immunology 2006 Oct 15;177(8):5163-8.