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Jack Lawler, PhD

Professor, Department of Pathology, Harvard Medical School

Director, Division of Cancer Biology and Angiogenesis, Pathology, Beth Israel Deaconess Medical Center

Contact Info

Jack Lawler
Beth Israel Deaconess Medical Center
99 Brookline Avenue
Boston, MA, 02215
Mailstop: Research North, Rm 270C
Phone: 617-667-1694
Fax: 617-667-3591
jlawler@bidmc.harvard.edu

Assistant

Ibelca (Evey) Fernandez
Division of Molecular & Vascular Medicine, Center for Vascular Biology Research
Beth Israel Deaconess Medical Center
99 Brookline Ave
Boston, MA, 02215
Mailstop: RN-280
Phone: 617-667-2918
Fax: 617-667-3591
iafernan@bidmc.harvard.edu

DF/HCC Program Affiliation

Angiogenesis, Invasion and Metastasis, Leader

DF/HCC Associations

Member, Center Scientific Council

Research Abstract

Thrombospondin-1 (TSP-1) and -2 are extracellular, calcium-binding proteins that regulate cellular phenotype by orchestrating the assembly of multiprotein complexes on the cell surface. These complexes include CD36, transforming growth factor beta, proteoglycans, integrins and integrin associated proteins. Thrombospondin-1 on the cell surface inhibits (1) proliferation of endothelial cells and tumor cells in vitro, (2) endothelial cell migration and angiogenesis, and (3) the growth of experimental and naturally occurring tumors in vivo. To establish a role for TSP-1 in the progression of spontaneously occurring tumors that arise at orthotopic sites in vivo, we have crossed mice that are deficient in TSP-1 with mice that are deficient in p53. Mice that lack TSP-1 exhibit decreased survival and altered tumor specturm. Consistent with these observations, overexpression of TSP-1 inhibits tumor growth and angiogenesis. In addition, systemic injection of recombinent type 1 repeats of TSP-1 inhibits the growth of tumors formed from the subcutaneous injection of B16F10 melanoma cells. These data indicate that tumor growth is inversely proportional to TSP-1 protein expression and that down-regulation of TSP-1 is involved in tumor progression.

Publications

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