Simeon E. Goldblum, MD
Professor of Medicine and Pathology, ID
Associate Director for Basic Research, MBRC

MD: University of Pittsburgh, 1973

Phone:(410) 706-5504
Fax: (410) 706-5508
E-mail: sgoldblu@medicine.umaryland.edu
Address:
Veterans Affairs Medical Center
Medical Services (111)
10 N. Greene Street--Room 5D-137
Baltimore, MD 21201

RESEARCH INTERESTS

Regulation of endothelial cell-cell adherens junction integrity and paracellular pathway function.

Our laboratory is interested in the intracellular effector mechanisms that couple specific receptor-ligand interactions with opening of the endothelial paracellular pathway. More specifically, we have focused on the tyrosine phosphorylation signaling events that regulate protein-protein interactions within the zonula adherens multiprotein complex, actin organization, and cell-cell homophilic adhesion. Our studies have included bacterial constituents (eg: lipopolysaccharide or endotoxin, staphylococcal enterotoxin B) and members of a family of novel counteradhesive proteins (eg: thrombospondin-1 and SPARC i.e. Secreted Protein Acidic and Rich in Cysteine). More recently, we have begun to study a receptor protein tyrosine phosphatase (PTP), PTPmu, that associates with and restrains tyrosine phosphorylation of zonula adherens proteins.

In a collaborative project with the laboratory of Dr. Alan S. Cross, we are engaged in studies of endogenous sialidases and the role of desialylation of surface structures on neutrophils and the endothelial barrier and how these events regulate neutrophil adherence to and migration across the endothelium. In another collaboration with the laboratory of Dr. Alessio Fasano, we are studying the signaling events that couple stimulation by either the prokaryotic protein, zonula occludin toxin (ZOT), or the eukaryotic homologue, zonulin, with tight junction disassembly.

RECENT PUBLICATIONS

Bannerman DD, Sathyamoorthy M, and GOLDBLUM SE. Bacterial Lipopolysaccharide Disrupts Endothelial Monolayer Integrity and Signaling Events Through Caspase Cleavage of Adherens Junction Proteins. J Biol Chem 1998, 273:35371-35380.

GOLDBLUM SE. Young BA, Wang P, and Murphy-Ullrich JE. Thrombospondin-1 induces tyrosine phosphorylation of adherens junction proteins and regulates an endothelial paracellular pathway. Mol Biol Cell 1999, 10:1537-1551.

Fasano A, Not T, Wang W, Uzzau S, Berti I, Tommasini A, and GOLDBLUM SE. Zonulin, a newly discovered modulator of intestinal permeability and its expression in Coeliac Disease. Lancet 2000, 355:1518-1519.

Cross AS, Sakarya S, Rifat S, Held TK, Drysdale B-E, Grange PA, Cassels FJ, Wang L-X, Stamatos NM, Farese A, Casey D, Powell J, Bhattacharjee AK, Kleinberg M, and GOLDBLUM SE. Recruitment of murine neutrophils in vivo through endogenous sialidase activity. J Biol Chem 2003, 278:4112-4120.

Young BA, Sui X, Kiser TD, Hyun SW, Wang P, Sakarya S, Angelini DJ, Schaphorst KL, Hasday JD, Cross AS, Romer LH, Passaniti A, and GOLDBLUM SE. Protein tyrosine phosphatase activity regulates endothelial cell-cell interactions, the paracellular pathway and capillary tube stability. Am J Physiol 2003, 285:L63-L75.

Sakarya S, Rifat S, Zhou J, Bannerman DD, Stamatos NM, Cross AS, and GOLDBLUM SE. Mobilization of neutrophil sialidase activity desialylates the pulmonary vascular endothelial surface and increases resting neutrophil adhesion to and migration across the endothelium. Glycobiology 2004;14:481-94.

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To contact us:

Phone: 410-706-7560
Fax: 410-706-4619
E-mail: kvardjan@ihv.umaryland.edu

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