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Faculty Zihai (Zack) Li
Associate Professor of Immunology and Medical Oncology
zli@up.uchc.edu
- M.S., Chinese Academy of Medical Sciences
- M.D., Henan Medical College
- Ph.D., Mount Sinai School of Medicine
- Medical Intern/Residency, Albert Einstein College of Medicine
- Oncology Fellowship, University of Washington and Fred Hutchinson
Cancer Research Center
- Immunology Graduate
Program
- Accepting Lab Rotation Students: Summer '08, Fall '08,
Spring '09
Areas of Interest:
Dr. Li’s laboratory is primarily interested in the mechanism of immune
regulation by the innate immunity in the context of tumors, infections
and autoimmune diseases. By understanding how the immune system deals
with microbes, tumors and self, we aim to design effective vaccines and
therapeutics against cancer and infectious diseases. Presently our study
focuses on two classes of proteins: heat shock proteins (HSPs) and
Toll-like receptors (TLRs), both of which have been implicated as master
regulators of immunity. We and others have discovered recently that the
function of TLRs is dependent on the integrity of a HSP gp96 (or grp94)
in the endoplasmic reticulum (Harding C.V. gp96 leads the way for
Toll-like receptors. Immunity. 2007 26:141-3). Furthermore,
depending on the level and location, changes of gp96 expression can
initiate systemic autoimmune diseases as well as tumor-specific
immunity, which have a significant clinical relevance. Using a
combination of genetic, cell biological, biochemical and immunological
tools, we aim to pinpoint the precise mechanism of TLR-gp96 interaction
and the implications of such in hematopoiesis and in the functions of
various cellular components in the immune system. Our study has a broad
implication in understanding how the immune system operates in light of
the critical roles of TLR in the evolution, function and regulation of
the immune system.
Lab Rotation Projects:
We take pride in sharing our expertise with trainees at all levels
including graduate students, medical residents, clinical fellows as well
as postdoctoral fellows. At the same time, trainees are expected to be
challenged experimentally and intellectually in the laboratory. They are
encouraged to choose projects under the general conceptual frame as
outlined above and are expected to function independently.
Post Docs:
We are seeking highly motivated postdoctoral fellows to lead a recent
NIH-awarded project. Ideal candidates should have a Ph.D. in immunology
and have a strong background in cellular immunology and biochemistry.
Send your CV and names of three references to Dr. Li (zli@up.uchc.edu).
We have
demonstrated recently that HSP gp96 is a master chaperone for TLRs and
macrophage-specific
gp96 null mice are highly susceptible to Listeria infection. Shown are
confocal images of spleen sections from uninfected wild type mice
(left), Listeria-infected wild type mice (middle) and macrophage-specific
gp96 null mice (right) (red: Listeria, green: Gr1+
granulocytes, blue: B220+ B cells) (Images from Yi Yang in
the laboratory)
Selected Publications:
Yang Y, Liu B, Dai J, Srivastava PK, Zammit DJ, Lefrancois L, Li Z
(2007) Heat shock protein gp96 is a master chaperone for Toll-like
receptors and is important in the innate function of macrophages.
Immunity 26(2):215-26.
Dai J, Liu B, Ngoi SM, Sun S, Vella AT, Li Z (2007) TLR4
Hyperresponsiveness via cell surface expression of heat shock protein
gp96 potentiates suppressive function of regulatory T cells. J
Immunol 178(5):3219-25.
Dai J, Liu B, Cua DJ, Li Z (2007) Essential roles of IL-12 and
dendritic cells but not IL-23 and macrophages in lupus-like diseases
initiated by cell surface HSP gp96. Eur J Immunol 37(3):706-715.
Liu B, Yang Y, Dai J, Medzhitov R, Freudenberg MA, Zhang PL, Li Z.
(2006) TLR4 up-regulation at protein or gene level is pathogenic for
lupus-like autoimmune disease. J Immunol 177(10):6880-8.
Li Z, Qiao Y, Liu B, Laska EJ, et al. (2005) Combination of imatinib
mesylate with autologous leukocyte-derived heat shock protein 70 and
chronic myelogenous leukemia. Clin Cancer Res 11(12):4460-8.
Yang Y, Li Z (2005) Roles of heat shock protein gp96 in the ER
quality control: redundant or unique function? Mol Cells
20(2):173-82.
Zheng H and Li Z (2004) Cutting Edge: Cross-presentation of
cell-associated antigens to MHC class I molecule is regulated by a major
transcription factor for molecular chaperones. J Immunol 173(10):5929-33.
DeFillipo AM, Dai J, Li Z (2004) Heat shock-induced dendritic cell
maturation is coupled by transient aggregation of ubiquitinated proteins
independently of heat shock factor 1 or inducible heat shock protein 70.
Mol Immunol 41(8):785-92.
Millar DG, Garza KM, Odermatt B, Elford AR, Li Z and Ohashi PS (2003)
Hsp70 promotes antigen presenting cell function and converts T cell
tolerance to autoimmunity in vivo. Nat Med 9(12):1469
–1476.
Liu B, Dai J, Zheng H, Stoilova D, Sun S and Li Z (2003) Cell surface
expression of an endoplasmic reticulum resident heat shock protein gp96
triggers MyD88-dependent systemic autoimmune diseases. Proc Natl Acad
Sci USA 100:15824-15829.
Zheng H, Benjamin IJ, Basu S and Li Z (2003) Heat shock factor 1 -
independent activation of dendritic cells by heat shock: implication for
the uncoupling of heat-mediated immunoregulation from heat shock
response. Eur J Immunol 33:1754-1762.
Dai J, Liu B, Caudill MM, Zheng H, Qiao Y, Podack E AND Li Z (2003)
Cell surface expression of heat shock protein gp96 enhances
cross-presentation of cellular antigens and the generation of
tumor-specific T cell memory. Cancer Immun 3:1.
Liu B, DeFilippo A and Li Z (2002) Overcoming immune tolerance to
cancer by heat shock protein vaccines. Mol Cancer Ther 1:
1147-1151.
Li Z, Dai J, Zheng H, Liu B and Caudill M (2002) An integrated view
of the roles and mechanisms of heat shock protein gp96-peptide complex
in eliciting immune response. Front Biosci 7:731-751.
Li Z, Menoret A and Srivastava PK (2002) Roles of heat shock proteins
in antigen presentation and cross-presentation. Curr Opin Immunol
14:45-51.
Zheng H, Dai J, Stoilova D and Li Z (2001) Surface targeting of an
intracellular heat shock protein gp96 induces dendritic cell maturation
and anti-tumor immunity. J Immunol 167:6731-6735 (*co-first
authors).
Caudill M and Li Z (2001) HSPPC-96: a personalized cancer vaccine.
Exp Opin Bio Ther 1(3):539-548.
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