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Faculty
 
lu_small.jpg Binfeng Lu , Ph.D.
Associate Professor
E1047 BST (Office)
E1017 BST (Lab)
Pittsburgh, PA 
Phone: 412.648.9339
Email: binfeng@pitt.edu
Fax: 412.383.8098
Faculty Research Interests
 
Research Interests
The lab is interested in discovery of novel molecular and cellular pathways regulating key steps of T cell-mediated immune responses in antitumor immunity and autoimmunity. Such studies will shed new light on immunotherapy for cancer and autoimmune diseases.

1: Regulation of ROS-triggered molecular responses in T cells and other immune cells in autoimmunity and cancer immunity.

ROS are important for T cells both as a second messenger and as a key inflammatory mediator within the cancer microenvironment and inflamed tissues. The molecular mechanisms underlying T cell responsiveness to ROS is unclear. In addition, how ROS shapes T-cell-mediated immune responses in vivo and how T cells adapt to high levels of ROS in inflamed tissues are largely unknown. We have recently found that ROS homeostasis in T cells is regulated by autophagy. This leads to our current interest in defining the role of autophagy in regulating ROS in T cells. We are also interested in studying the transcriptional factors induced by ROS in T cells as well as innate cells. Our current interest is to delineate key transcription factors in response to ROS in T cells and further understand how these transcription factors regulate T cell-mediated autoimmune responses and antitumor immune responses.

2: Discovery of novel targets for improving T cell-mediated immunotherapy of cancer.

We are interested in discovering new targets for immunotherapy of cancer through studying the molecular basis underlying effective antitumor T cell immune responses in human and mice. We have found that IL-33R is up-regulated by T-bet and Eomes and 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. Although IL-33 and other cytokines such as IL-12 and IL-2 can inhibit tumor progression in mice, the cytokine-based approach has only achieved modest and transient antitumor effects in human. Therefore, another interest of ours is to understand what are the “brakes” that limit an otherwise successful cancer immunotherapy by cytokines. Our recent work has identified several molecules that have such functions. We found 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, we are interested in translating these new findings to the clinical setting, which should greatly benefit cancer patients.
 
Education
Postdoc - Yale University (1998-2003)

Ph.D. - Columbia University (1998)

B.S. - Tsinghua University, Beijing (1992)
 
Academic Affiliation
Associate Professor of Immunology, University of Pittsburgh

Member, University of Pittsburgh Cancer Institute
 
Selected Publications
Gang Li, Qianting Yang, Yibei Zhu, Hongrui Wang, Xinchun Chen, Xueguang Zhang, Binfeng Lu, T-bet and Eomes regulate the balance between the effector/central memory T cells versus memory stem T cells. 2013 June 27. PLoS ONE 8(6): e67401. doi:10.1371/journal.pone.0067401

Lu-jun Chen, Xiao Zheng, Yue-ping Shen, Yi-bei Zhu, Qing Li, Chang-ping Wu, Xue-guang Zhang, Bin-feng Lu*, Jing-ting Jiang*. Higher numbers of T-bet+ intratumoral lymphoid cells correlate with better survival in gastric cancer. Cancer Immunol Immunother. 2012 Oct 23. [Epub ahead of print] PubMed PMID: 23090288. *co-corresponding authors.

X Gao, Y Zhu, G Li, H Huang, G Zhang, F Wang, J Sun, Q Yang, X Zhang, B Lu. TIM-3 Expression Characterizes Regulatory T Cells in Tumor Tissues and Is Associated with Lung Cancer Progression. PLoS One. 2012;7(2):e30676. Epub 2012 Feb 17.

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. doi: 10.1002/eji.201141629. [Epub ahead of print] PMID: 21887788

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. doi: 10.1038/cdd.2011.78. [Epub ahead of print]

Lu-jun Chen, Jing Sun, Hong-ya Wu, Shu-ming Zhou, Yan Tan, Ming Tan, Bao-en Shan, Bin-feng Lu*, Xue-guang Zhang*. B7-H4 expression associates with cancer progression and predicts patient's survival in human esophageal squamous cell carcinoma. Cancer Immunol Immunother. 2011 Apr 26. [Epub ahead of print], *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. [Epub ahead of print] PMID: 20725832. *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. [Epub ahead of print]

Ju S, Zhu Y, Liu L, Dai S, Li C, Chen E, He Y, Zhang X, Lu B. Gadd45b and Gadd45g are important for anti-tumor immune responses. Eur J Immunol. 2009 Nov;39 (11):3010-8. PMID: 19688743

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.
 
Grants
Title: Cellular and molecular mechanisms underlying IL-33-mediated anti-tumor immunity
Agency: NIH
Role: P.I.
Funding Period: 2012-2014

Title: Gene Expression Profiling of Thymic Epithelial Cells from Thymona
Agency: CTSI
Role: P.I.
Funding Period: 2013
 
Lab Personnel
Postdoctoral Associates
Ines Gonzalez-Garcia, Ph.D.
Lin Liu, Ph.D.
Yibei Zhu, Ph.D.

Research III
Christen Shiber

Visiting Scholar
Qianting Yang, MD
 
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