The Sachais Lab
602/605A Stellar-Chance
University of Pennsylvania
|
The Sachais Lab 602/605A Stellar-Chance University of Pennsylvania |
||
|
|||
|
Bruce Sachais, MD, PhD Assistant Professor Director of Transfusion Services, HUP Pathology and Laboratory Medicine University of Pennsylvania 605A Stellar Chance 422 Curie Bvd. Philadelphia, PA 19104 Office: 215-898-0568 Lab: 215-898-0569 Fax: 215-573-0252 |
My laboratory is primarily interested in the biology and structure of platelet factor 4 (PF4). PF4 is a cationic protein found in the a-granules of platelets and is released upon platelet activation. It binds avidly to glycosaminoglycans on the surface of endothelial cells and is known to inhibit anti-thrombin III, resulting in increased clotting. We
are interested in the role of PF4 in several diseases, specifically atherosclerosis
and heparin induced thrombocytopenia (HIT).
We have found that PF4 is localized in atherosclerotic lesions
and that the presence of PF4 correlated with pathological and clinical
disease progression. Further,
we have found that in vitro PF4 inhibits endocytosis of the LDL
receptor, resulting in decreased LDL degradation and retention of LDL
on the cell surface. Current studies are underway to further understand the cellular
and molecular mechanisms responsible for this phenomenon and to examine
the effects of PF4 on other lipoproteins and lipoprotein receptors.
In vivo experiments are currently underway to further our
understanding of these phenomena. Another project in the lab is examining the molecular mechanisms of HIT. This rare but serious complication of heparin therapy is known to involve the recognition of PF4:heparin complexes by pathogenic auto-antibodies. It is also known that altering the ratio of heparin to PF4 alters the recognition of the complexes. Our working hypothesis is that the structure of the complexes formed at different heparin:PF4 ratios differs and that the structural changes are important for the expression of disease. We are investigating these structural changes and how these changes effect pathogenesis of HIT. Both in vitro and in vivo systems are being employed. |
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
