Joseph A. Madri, Ph.D., M.D.

Training:

M.D. Indiana Univ., Bloomington, IN, 1975
Residency: Yale-New Haven Hospital
Fellowship: Yale School of Medicine
Ph.D. (Chemistry), Indiana Univ., Bloomington, IN, 1973
M.S. (Biology), St. John's University, Jamaica, NY, 1969
B.S. (Biology), St. John's University, Jamaica, NY, 1967

Expertise:

Connective tissue disorders. Cell- Matrix and Cell-Cell Interactions, Integrin-Mediated Signaling, Cardio-vascular development, Angiogenesis and Vascular Biology . Other interests include inflammation, T-cell-Endothelial cell interactions.

Research Interests:

Research Focus: The interests of my laboratory center around investigations of signaling pathways stimulated following endothelial cell-cell and endothelial cell-extracellular interactions and how they influence the processes of Vasculogenesis, angiogenesis and transendothelial migration.
Endothelial cells play central roles in the development, growth and maintenance of the vascular system as well as in the processes of inflammation, repair and metastasis. Vascular cell homotypic and heterotypic interactions and vascular cell interactions with the surrounding matrix, soluble factors and circulating blood cells (leukocytes, monocytes and lymphocytes), in part, direct the vascular cells' responses; yet little is known about these complex interactions and the mechanisms involved in information transduction from the extracellular environment to the cell nucleus.
We are currently investigating the roles of selected homotypic and heterotypic cell adhesion molecules (PECAM-1), integrins (selected beta1, beta 2 and beta 3 integrins), junction associated molecules and extracellular matrix components in modulating vascular cell and T cell behavior (attachment, spreading, proliferation, migration, interactions with mononuclear (T) cells and angiogenesis). Specific projects in the laboratory currently include:
1) Elucidation of the roles of the cytoplasmic domains of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1/CD31) in modulating endothelial and T cell behavior, vascular development and dermal wound healing as well as the signaling mechanisms involved. We are investigating how differential tyrosine and serine phosphorylation of the PECAM-1 cytoplasmic domain modulates associations with specific proteins including beta- and gamma-catenin; STAT3 & 5, c-src, SHP-2 and small G proteins.
2) Identification and elucidation of the signal transduction pathways activated following T cell alpha4beta1 integrin-endothelial cell VCAM-1 binding and T cell PECAM-1 signaling prior to, during and following T cell transmigration into tissues. We are investigating the mechanisms of induction, clustering and activation of T cell and endothelial cell matrix metalloproteinase-2 [MMP-2 ], membrane type matrix metalloproteinase [MT1-MMP/MMP-14], matrix metalloproteinases [MMP-9] and CD44. Several knock out mouse strains (MMP-2 KO, MMP-9 KO, MMP-14 and CD31 KO) are also utilized in animal models of autoimmune encephalomyelitis.
3) Elucidation of the mechanisms of hypoxia-driven cerebral angiogenic responses noted in the premature infant population and their association with neurodevelopmental handicaps. Animal, organ and tissue culture models of chronic hypoxia coupled with cDNA array analysis are used to investigate the responses of the cerebral microvascular endothelial cells and the roles of the vasculature in causing resultant neurodevelopmental handicaps.
4) Elucidation of the mechanisms of the hyperglycemia-driven vasculopathy in the vitilline and embryonic circulations of murine conceptuses noted in maternal diabetes. Cultures of whole murine conceptuses and endocardial cushions are utilized along with confocal immunofluorescence microscopy, immunoprecipitation and immunoblotting techniques. Specifically, we are investigating the roles of VEGF and VEGF receptors, PECAM-1 (CD31) and matrix metalloproteinases in this hyperglycemia-induced vasculopathy.

Professional Service:

American Heart Association
Member, Editoral Board of 'Laboratory Investigation 1991-95
Member, Editorial Board of Angiogenesis 1997-2006
Member, Editorial Board of Endothelium 1999-present
Member, Editorial Board of Arteriosclerosis 1983-99
Member, Editorial Board, American Journal of Pathology 1984-92
Associate Editor, Amercian Journal of Pathology 1992-96
Executive Editor, Laboratory Investigation 1995-2003
Associate Editor, FASEB Journal 2002-2006
Member, Editorial Board of Journal of Cellular Physiology 2006-present
Reviewer for Pathology A and Pathobiological Chemistry Study Sections, The Dental Institute, the Cancer Institute, the Atheroslerosis SCOR, Senior Fellowships Special Study Section and Developmental Cardiobiology Program Projects Study Section of The National Institutes of Health 1983-present
Sigma Xi
Phi Lambda Upsilon
American Chemical Society
American Association of Pathologists
International Academy of Pathology
American Society for Cell Biology
New York Academy of Science
Diplomate: American Board of Pathology 1979

Selected Publications: