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FRISC: The Faculty Research Interests Science Comparator |
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Assistant Professor of Pathology
Immunology
Office: (214) 648-4111
FAX: (214) 648-4070
Email: estess.pila@pathology.swmed.edu
My laboratory studies structure/function relationships in
adhesion receptors of the immune system. These molecules are critical for the specialized
movement of leukocytes from blood into lymphoid organs and into inflamed tissues. They may
also have a role in the traffic of malignant cells into sites of metastasis. We use
molecular biology in conjunction with in vitro and in vivo mouse models to
characterize these receptors and the effects resulting from their manipulation. Our
interests are focused on lymphocyte adhesion molecules and their counter-ligands on
vascular endothelial cells.
Effector and/or memory T cells are known to express
increased surface levels of the receptor CD44. We have shown that the interaction of
activated CD44 with its major ligand on vascular endothelium (hyaluronan) can mediate
primary lymphocyte adhesion, resulting in extravasation at inflammatory sites. We have
also shown that the activation of CD44 and induction of primary adhesion occurs directly
through T cell receptor initiated signaling. These studies have been extended to in
vivo murine models of inflammation, including superantigen induced inflammation,
psoriasis, arthritis, SLE, and diabetes. Concurrent studies on endothelial cells have
demonstrated that hyaluronan expression is regulated in response to proinflammatory
cytokines. The signaling pathways for induction of both CD44 (lymphocyte) and hyaluronan
(endothelial cell) expression are actively under investigation.
We are also analyzing CD44-mediated primary adhesion in
patients with autoimmune disease and have demonstrated a correlation between disease
exacerbation and expression of activated CD44 on peripheral blood lymphocytes. In
addition, we are evaluating hematopoietic malignancies to determine if the association
between CD44 and malignancy is related to its participation in the process of metastasis.
Selected Publications:
Siegelman, M.H. , DeGrendele, H.C., and Estess, P.
(1999) Activation and interaction of CD44 and hyaluronan in immunological systems. J.
of Leukocyte Biology 66:in press.
Estess, P., Nandi, A., Mohamadzadeh, M., and Siegelman,
M.H. (1999) IL-15 induces endothelial hyaluronan expression in vitro and promotes
activated T cell extravasation through a CD44 dependent pathway in vivo. J. of
Experimental Medicine 190:9.
Catalina, M.D., Estess, P., Siegelman, M.H. (1999)
Selective Requirements for Leukocyte Adhesion Molecules in Models of Acute and Chronic
Cutaneous Inflammation: Participation of E- and P- but not L-selectin. Blood
93:580.
Estess, P., DeGrendele, H.C., Pascual, V., Siegelman, M.H.
(1998) Functional Activation of Lymphocyte CD44 in Peripheral Blood is a Marker of
Autoimmune Disease Activity. J. of Clinical Investigation 102:1173
Mohamadzadeh M., DeGrendele HC, Arizpe H, Estess P, and
Siegelman MH (1998) Proinflammatory Stimuli Regulate Endothelial Hyaluronan Expression and
CD44/HA Dependent Primary Adhesion. J. of Clin Investigation 101:97
DeGrendele HC, Estess P and Siegelman MH (1997) Activated
T Cell Extravasation into an Inflammatory Site is Mediated by CD44 Interactions with
Hyaluronate. Science 278:672
DeGrendele HC, Kosfiszer M., Estess P and Siegelman MH
(1997) CD44 Activation and Associated Primary Adhesion Is Inducible via T cell Receptor
Stimulation. J. of Immunology 159:2549
DeGrendele HC, Estess P, Picker LJ and Siegelman MH (1996)
CD44 and its ligand hyaluronate mediate rolling under physiologic flow: A novel
lymphocyte/endothelial cell primary adhesion pathway. J. of Exp Medicine 183:1119
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Last updated: 17 Nov 2000
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