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Sanford Shattil

Affiliation: UCSD SOM

Professor of Medicine

sshattil@ucsd.edu
Phone: (858)822-6425

Biography

1985-95 Professor of Medicine and Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA.
1994 Visiting Scientist, Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA.
1995-2001 Professor, Departments of Vascular Biology and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA.
1996-2004 Professor, Graduate Program in Macromolecular and Cellular Structure and Chemistry, The Scripps Research Institute, La Jolla, CA.
2001-2004 Professor, Division of Vascular Biology, Department of Cell Biology and Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA.
2004- Professor of Medicine, University of California San Diego, La Jolla, CA

Research Summary

The long term goal of Dr. Shattil's research program is to understand the mechanisms by which platelets become activated at sites of vascular injury and yet are quiescent in the normal circulation. His research program is currently focused in three principal areas related to b3 integrin adhesion receptors.
 
1) Mechanisms of regulation of b3 integrin affinity and avidity. Integrins aIIbb3 and aVb3 play central roles in platelet aggregation and endothelial cell function, respectively. Recombinant monoclonal antibodies have been developed in this laboratory that discriminate between different states of activation of the extracellular portions of these integrins. These antibodies have been constructed such that they recognize integrins from multiple species, including mouse and man, and they have demonstrated that the activation states of aIIbb3 and aVb3 are tightly regulated in normal cells. These probes are currently being used in genetic screens of primary cells, including platelets and megakaryocytes, to identify genes involved in integrin activation. They are also being used to study the role of aVb3 affinity and avidity modulation in endothelial cell adhesion and migration.
 
2)  Mechanisms of "outside-in" signaling across b3 integrins. Many proteins undergo increased phosphorylation on tyrosine residues when adhesive ligands bind to platelet integrins. A series of molecular and cell biological approaches are being used to identify the enzymes, substrates and adaptor molecules involved in integrin-mediated cell signaling and to establish their roles in adhesion dependent events, particularly cytoskeletal reorganization.
 
3) Development of new mouse models of platelet involvement in hemostasis and thrombosis. We are developing transgenic mice that express conditional alleles of aIIbb3 and relevant signaling molecules in a tissue-specific fashion (e.g., platelets and megakaryocytes). Expression of these alleles will allow us to cluster aIIbb3 or specific signaling molecules in a controlled manner using chemical inducers of dimerization, and thereby activate platelets in vivo. This experimental system will be used to identify the basic mechanisms of platelet stimulus-response coupling and to assess the precise roles of platelet and aIIbb3 activation in murine hemostasis and arterial thrombosis.

References

References From PubMed (NCBI)

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