- Professor, Department of Pathology, Committee on Immunology, Committee on Cancer Biology, Committee on Molecular Medicine/MPMM
Ph.D., University of Miami, 1990
M.D., Shanghai Medical University, 1983
The University of Chicago
924 East 57th Street
Chicago, Illinois 60637
Phone: (773) 702-0929
Website (Department of Pathology)
My clinical background and strong interest in basic immunobiology have led me to integrate basic research into more pathogenesis and treatment of diseases. The basic research in my laboratory is focused on understanding the biological consequences arising from the interaction between core molecules of the TNF superfamily, lymphotoxin (LT or TNFSF1) and LIGHT (TNFSF14), on lymphocytes, and their receptor, LTbR, on stromal cells. This research has contributed substantially to the definition of the critical role these molecules play in the development and function of lymphoid tissues. Our recent studies have defined the roles of these molecules in infectious and tumor immunity in mouse models and human patients. Our research includes four major themes.
Critical role for lymphotoxin in the development and function of primary, secondary, and tertiary lymphoid tissues
The relative contributions of lymphoid tissues and non-lymphoid tissues to various immune responses had not been defined previously due to the lack of appropriate animal models and the complicated nature of the issues involved. Our pioneering studies have revealed the essential role of LT and TNF for the development and maintenance of lymphoid tissues. Using LT-deficient mice, or antibody or soluble receptor blockade, we generated unique mouse models that lack various sets of secondary lymphoid tissues to define the roles of these structures in various tissues for different types of immune responses. We have been studying the development and maintenance of complex lymphoid architecture using these models; Lately, we are exploring novel LTbR-stimulated NFkB pathways shape the development and function of lymphoid tissues which are important for priming and tolerance.
1. To explore the role of LT-controlled gut immunity in bacterial and autoimmune colitis through regulating microbiota.
2. To define the role of ILC3 in regulating microbiota and immune responses. We have generated various conditional KO mice that defective RORgt or related regulatory factors such as STAT3 and Id2.
3. To study how lymphoid tissues are regulated at early and late phase.
Target tumor tissues to generate systemic immune responses
Lack of effective infiltration of immune cells and proper expression of co-stimulatory molecule prevent effective immune response against established tumor. Our understanding of the role of LIGHT on the LTbR-mediated lymphoid microenvironment and on its another receptor, HVEM (a costimulatory receptor) has allowed us to study the role of lymphoid-like microenvironment in autoimmune diseases and develop new strategies to target tumor with LIGHT to attract immune cells by LTbR signaling and activate T cells by HVEM inside tumor tissues. Indeed, local expression of LIGHT inside tumors causes development of lymphoid-like structures within those tumors. This allows the rapid recruitment of naïve and activated T cells into tumor sites and generates an effective anti-tumor response. Our future studies will attempt to reveal the cellular and molecular mechanisms governing tumor evasion and barriers in tumor bearing host. These basic studies will also guide us in the development of novel approaches to immunotherapy to break tumor barriers and tumor induced tolerance.
1. To investigate the mechanisms by which antibody based immunotherapy. We will explore the role of antibodies in induction of cytokines, stress molecules, and Fc receptor mediated cross-priming. Currently, we have targeted CD20, HER2/neu and EGFR.
2. To investigate the mechanisms ablative radiation initiates DNA damage, stress induction for innate and adaptive immunity that control tumor. We will explore cellular and molecular mechanisms that are essential at initiating RT-mediated immunity
3. To investigate whether targeting tumors with a novel fusion protein, consisting of anti-tumor antibody genetically fused to various cytokines or danger signals can further amplify the ablative RT or anti-oncogenic antibody mediated immunity. We are exploring new fusion proteins that can change tumor environment and break tolerance inside tumor tissues.
4. To determine the effects of currently used chemotherapeutic agents on host immune responses
5. To determine the effect of endogenous danger signaling on triggering innate and adaptive immunity against tumor