Stanley E. D'Souza, Ph.D.

Stanley E. D'Souza, Ph.D.


Stanley E. D'Souza, Ph.D.
sedsou01@louisville.edu
Professor
University of Melbourne, Australia, 1985



Thrombosis and atherosclerosis are diseases that can occlude the blood vessel occlusion and obstruction of blood flow to organs. My laboratory is interested in dissecting the mechanisms that mediate cellular adhesive interactions on endothelial cells lining the inner wall of blood vessels that mediate vessel obstruction. Leukocytes and platelets adhere to the endothelium through cytokine-activated adhesion molecules, ICAM-1 and VCAM-1. We studied the signals generated upon ICAM-1 engagement and found that two unique tyrosine residues within the cytoplasmic sequence of ICAM- I become phosphorylated that results in the binding of a phosphatase (SHP-2) to ICAM-1. This association regulates various endothelial cells functions.

Our current research investigations are focused on:

The mechanisms mediating ICAM-1 processing and defining the enzymes involved in ICAM-1 shedding that may regulate the inflammatory process of leukocyte transmigration. In elucidating the role of unsaturated aldehydes such as acrolein and hexenal, products found as environmental pollutants, in the causation of cardiovascular diseases. Finally, we have a collaborative project on the vascular damage caused by water-borne metal toxicant, arsenic.

Publications:

  1. Gardiner, E.E. and D’Souza S.E. Sequences within fibrinogen and intercellular adhesion molecule-1 (ICAM-1) modulate signals required for mitogenesis. J. Biol. Chem. 274: 11930-11936, 1999.
  2. Pluskota, E., Chen, Y. and D’Souza, S.E. Tyrosine phosphatase SHP-2 associates with ICAM-1 to regulate cell survival. J. Biol. Chem. 275: 30029-30036, 2000.
  3. Tsakadze NL, Srivastava S, Awe SO, Adeagbo ASO, Bhatnagar A and D’Souza, S.E. Effect of unsaturated aldehyde acrolein on vasomotor responses in rat aortic rings. Am. J. Physiol., 285: H727-H734, 2003
  4. Tsakadze NL, Sithu SD, Sen U, English W, Murphy G, D’Souza, S.E. Tumor Necrosis Factor-α converting enzyme (TACE/ADAM-17) mediates the ectodomain cleavage of Intercellular Adhesion Molecule-1 (ICAM-1). J. Biol. Chem. 281: 3157-3164, 2006.
  5. Sithu SD, English WR, Olson P, Krubasik D, D Baker AH, Murphy G, D’Souza SE. Membrane Type 1- Matrix Metalloproteinase (MT1-MMP) Regulates Intracellular Adhesion Molecule-1 (ICAM-1) Mediated Monocyte Transmigration. J. Biol. Chem. 282 (34): 25010-25019, 2007.