The primary research interests of my lab include
Cancer Immunology and Immunotherapy, Biodefense, Immunopharmacology and
Immunotoxicology. Currently, we are pursuing research in the following specific
areas.
a. Cancer Immunology and Immunotherapy:
Interleukin-2 (IL-2) has been shown to be effective in the treatment of certain
types of cancer including human melanomas and renal cell carcinomas. However,
IL-2 therapy is accompanied by severe life-threatening toxicity characterized by
endothelial cell injury leading to vascular leak syndrome (VLS). We are
interested in reducing the toxicity associated with such therapy by preventing
the interaction of a molecule known as CD44 present on cytotoxic lymphocytes
with their ligands found on endothelial cells. Our studies are aimed at
addressing the role of various CD44 isoforms present on the lymphocytes that may
be involved in endothelial cell injury and tumor rejection. (Supported by NIH
grants R01 AI053703 and R01 HL058641).
We are also working on another project which involves studying the cellular and
molecular mechanisms by which bryostatin-1, a pharmacological agent used in the
treatment of cancer, can induce immunomodulation and thereby cause rejection of
tumors. Our initial studies have demonstrated that bryostatin-1 induces
dendritic cell maturation. Further studies are underway to examine whether
bryostatin serves as a ligand for the toll-like receptors (TLRs) on the
dendritic cells.
b. Biodefense:
Yet another area of our research is to examine the role of immune cells
including NK, NKT and T cells involved in acute lung injury induced by
staphylococcal enterotoxin which is a select agent designated by the Centers for
Disease Control and US Department of Agriculture. Furthermore, studies will be
carried out to develop strategies to block the toxicity. (Supported by NIH grant
R01 058300)
c. Immunopharmacology:
In a collaborative study, we also wish to address the downstream signaling
mechanisms involved in induction of apoptosis of T cells and dendritic cells by
delta9-tetrahydrocannabinol (THC), the active ingredient in marijuana. We are
specifically determining whether the death-receptor pathway or the mitochondrial
pathway or both are involved in apoptosis. Attempts are also underway to
determine whether other natural or synthetic selective cannabinoid receptor
agonists could be used in the treatment of diseases such as cancer and
autoimmunity. (Supported by NIH grant R01 DA016545).
d. Immunotoxicology:
Lastly, studies from our lab are aimed at delineating the mechanism by which
environmental pollutants such as TCDD (dioxin) and other endocrine disruptors
cause immunotoxic effects. We have demonstrated that Fas+ mice are more
sensitive than Fas- mice in their susceptibility to TCDD-mediated thymic atrophy
suggesting that Fas may be a molecule involved in TCDD-induced apoptosis of
thymocytes. Studies are in progress to determine the role of AhR in
dioxin-induced upregulation of Fas and Fas ligand. We are also addressing the
immunotoxic effects induced by exposure to TCDD during pregnancy in both the
mothers and the fetuses. Such alterations in the immune system could lead to
susceptibility to infections as well as development of autoimmunity, allergies
and cancer. (Supported by NIH grant R01 ES009098).
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Board of Trustees of the University of South Carolina
