Faculty Profile
Dr. Shattil
Sanford Shattil, M.D.
Professor of Medicine
Chief, Division of Hematology-Oncology
Director, Hematology-Oncology Fellowship Program
Office Address:
Division of Hematology-Oncology
University of California Medical Center
9500 Gilman Drive, MC-0726
La Jolla, CA 92093sshattil@ucsd.edu
FAX: (858) 822-6444
Education and Training
| BA | Psychology, University of Illinois | 1961-1964 |
| MD | University of Illinois College of Medicine | 1964-1968 |
| Intern/Resident | Boston City Hospital (Harvard) | 1968-1970 |
| Fellow | Hematology, Boston City Hospital, Thorndike Lab, Harvard | 1970-1971 |
Research Interests
Signaling Through Integrin Adhesion Receptors in Blood Cell Development and Function
Integrins represent a ubiquitous family of transmembrane adhesion receptors that transfer biological information between the extracellular and intracellular environments. The general term “integrin signaling” is often used to refer to this process, which is involved in regulating processes as diverse as embryonic development, synaptic plasticity of the nervous system, innate and adaptive immunity and the functions of circulating blood cells. Integrin signaling encompasses both “inside-out” signals that regulate integrin affinity and avidity for extracellular ligands and “outside-in” signals, whereby ligated integrins regulate anchorage-dependent cellular responses, such as cell motility and changes in gene expression. Defects in integrin signaling promote certain vascular, inflammatory and neoplastic disorders.
The focus of this laboratory is to unravel the molecular basis of integrin signaling as it pertains to hematopoietic and vascular cells, particularly platelets, their precursors cells- megakaryocytes, and endothelial cells. In this context, integrins are required for proliferation and differentiation of stem cells and hematopoietic progenitors into megakaryocytes, for platelet function in hemostasis and thrombosis, and for endothelial cell participation in wound healing and angiogenesis. Recent work from this laboratory using a number of experimental systems, including human platelets, genetically-modified mice, zebrafish and Drosophila, indicates that integrin signaling in these cell types is initiated by the interaction of these adhesion receptors with specific protein kinases, phosphatases and molecular adapters. One current challenge is to integrate the wealth of information obtained from these and other studies into a complete understanding of integrin signaling, with potential clinical implications for cardiovascular and neoplastic diseases.
Publications
Arias-Salgado, E.G., Haj, F., Dubois, C., Moran, B., Kasirer-Friede, A., Furie, B.C., Furie, B., Neel, B.G. and Shattil, S.J.: PTP-1B is an essential positive regulator of platelet integrin signaling. J. Cell Biol. 170:837-845, 2005.
Gaur, M., Kamata, T., Wang, S., Moran, B., Shattil, S.J. and Leavitt, A.D.: Megakaryocytes derived from human embryonic stem cells: a genetically tractable system to study megakaryocytopoiesis and integrin function. J. Thromb. Haemost. 4:436-442, 2006.
Han, J., Lim, C.J., Watanabe, N., Soriani, A., Ratnikov, B., Calderwood, D.A., Puzon-McLaughlin, W., Lafuente, E.M., Boussiotis, V.A., Shattil, S.J. and Ginsberg, M.H.: Reconstructing and deconstructing agonist-induced activation of integrin αIIbβ3 (platelet GP IIb-IIIa). Current Biology 16:1796-1806, 2006.
Kasirer-Friede, A., Moran, B.P., Nagrampa-Orje, J., Swanson, K., Ruggeri, Z.M., Schraven, B., Neel, B., Koretzky, G. and Shattil, S.J.: ADAP is required for normal αIIbβ3 activation by VWF/GP Ib-IX-V and other agonists. Blood 109:1026-1033, 2007.
Ablooglu, A., Kang, J., Handin, R., Traver, D. and Shattil, S.J.: The Zebrafish vitronectin receptor: Characterization of αV and β3 expression patterns in early vertebrate development. Dev. Dyn. 236:2268-2276, 2007.
Helsten, T.L., Bunch, T.A., Kato, H., Yamanouchi, J., Choi, S.H., Jannuzi, A.L., Ginsberg, M.H., Brower, D.L. and Shattil, S.J.: Differences in talin regulation of Drosophila and vertebrate integrin affinity by talin. Molecular Biol. Cell 19:3589-3598, 2008.
Watanabe, N., Bodin, L., Pandey, M., Krause, M., Coughlin, S., Boussiotis, V.A., Ginsberg, M.H. and Shattil, S.J.: Mechanisms and consequences of agonist-induced talin recruitment to platelet integrin αIIbβ3. J. Cell Biol. 181:1211-1222, 2008.
Coller, B.S. and Shattil, S.J.: The GP IIb/IIIa (integrin αIIbβ3) odyssey: a technology driven saga of a receptor with twists, turns and even a bend. Blood 112:3011-3025, 2008.
Ablooglu, A.J., Kang, J., Petrich, B.G., Ginsberg, M.H. and Shattil, S.J.: Anti-thrombotic effects of targeting αIIbβ3 signaling in platelets. Blood. Prepublished online November 12, 2008; 10.1182/blood-2008-09-180687.
Laboratory
Dr. Shattil moved his research laboratory from the Scripps Research Institute to the Department of Medicine at UC San Diego in July 2004. |
||
Laboratory Personnel
|
||
| Name | Title | Laboratory Focus |
| Ararat J. Ablooglu, Ph.D. | Assistant Project Scientist | Integrin biology in zebrafish and mice |
| Bryan Kahner, Ph.D. | Postdoctoral Fellow | G-protein signaling to integrins |
| Jian Kang, Ph.D. | Staff Research Associate | Integrin biology in zebrafish and mice; recombinant integrin antibodies |
| Ana Kasirer-Friede, Ph.D. | Associate Project Scientist | Platelet receptor signaling in flowing blood |
| Hisashi Kato, Ph.D. | Postdoctoral Fellow | Integrin signaling in neoplasia |
| Zhongji Liao, Ph.D. | Posdoctoral Fellow | Integrin/Src interactions in endothelial functions |
| John Mitsios, Ph.D. | Postdoctoral Fellow | Conditional vinculin knockout in platelets |
| Manjula Pandey | Staff Research Associate | Integrins and stem cells |
