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Research Interests
We are studying the mechanisms by which programmed cell death (apoptosis)
is regulated during T cell development and immune responses. Our previous
work have demonstrated that activation of immature T cells and T cell
hybridomas leads to apoptosis. We have also shown that proto-oncogene
c-myc plays a pivotal role in this process. Our recent studies have demonstrated
that c-myc is required for activation-induced expression of Fas ligand
(FasL). Although Fas is also induced by activation, its expression does
not require c-myc; instead it requires translocation of protein kinase
C (PKC). Since the expression and subsequent interaction of Fas and FasL
is absolutely required for activation-induced T cell apoptosis, the determination
of the molecular mechanisms of c-myc-mediated FasL expression and PKC-mediated
Fas expression will lead to fundamental understanding of the regulation
of the immune system.
Cell proliferation also requires coordinated activation of genes involved
in the cell cycle as well as genes for maintaining cell viability. In
another project, we have investigated the relationship between cell proliferation
and apoptosis by activating cells with mitogenic cytokines in the absence
of serum. When stimulated with cytokines without serum, several cell types
underwent apoptosis. In the presence of serum, or simply in the presence
of transferrin, apoptosis does not occur. Either serum or transferrin
activated the cell survival gene bcl-2, while mitogenic cytokines mainly
induced Bax. By transfecting cells with an expression cDNA, we have identified
a novel cell survival gene, SRG-1, bearing putative Bcl-2 homology domain
1 (BH1) of the Bcl-2 family proteins. This gene is differentially induced
upon cytokine and serum stimulation and is expressed in selected tumors,
but is not detected in most normal tissues. We are currently characterizing
SRG-1 and determining its role in regulation of cell viability and tumorigenesis.
Selected Publications Top
Contact Information Top
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