Department of Regenerative Medicine and Cell biology
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Samar M. Hammad, Ph.D.
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Education: BS Zoology, Kuwait
Univ. |
Research Activity: The Hammad laboratory is interested primarily in
lipoprotein-related research. Recently, our focus has
been on investigating the sphingolipid signaling mechanisms
which mediate the survival of foam cells (lipid laden
macrophages) and their sustained cell activation in response
to modified lipoproteins and lipoprotein-immune
complexes. The transformation of macrophages into foam
cells is a critical event in the development of
atherosclerosis and defining mechanisms mediating foam cell
formation and determining the role of foam cells in the
pathology of atherosclerosis is an area of great clinical
relevance. Our goal is to uncover targets in the
signaling pathway such as receptors and/or sphingolipids that
can have therapeutic implications for blocking cytokine
release and prevention of vulnerable atherosclerotic
plaques. Macrophages internalize oxidized LDL immune
complexes (oxLDL-IC) via the Fc-y receptor and transform into activated foam cells. Our
data demonstrated that exposure of human monocytic cells to
oxLDL-IC leads to increased cell survival compared to oxLDL
alone. We examined the effect of oxLDL-IC on sphingosine
kinase 1 (SK1), an enzyme implicated in mediating pro-survival
and inflammatory responses through the generation of the
signaling molecule sphingosine-1-phosphate (S1P).
Intriguingly, oxLDL-IC, but not oxLDL alone, induced an
immediate translocation and release of SK1 into the
conditioned medium. This finding indicates that S1P may
be generated extracellularly in response to modified LDL
immune complexes and may therefore promote cell survival and
prolong cytokine release by activated macrophages. Our
goal is to uncover mechanisms by which oxLDL-IC suppress
apoptosis of foam cells, and reveal specific targets in the
signaling pathway that can have therapeutic implications for
blocking cytokine release and to prevent formation of
vulnerable plaques. Another area of research, with which I am involved and
collaborating with Dr. W.S. Argraves in the department, is the
function of the newly discovered HDL receptor, Cubilin, in
mediating uptake, degradation and transcytosis/exocytosis of
HDL. Cubilin is expressed in the renal proximal tubule,
intestine, and yolk sac endoderm. Our goal is to
determine the physiological significance of cubilin-mediated
renal uptake of filterable forms of HDL to HDL
homeostasis. A decreased level of plasma HDL is a major
risk factor for coronary atherosclerosis. |
Recent Publications:
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