Simeon Goldblum, M.D. Professor of Medicine and Pathology
Department:
Medicine
UMGCC Research Program:
Hormone Responsive Cancers Program
Education/Training:
College Degree:
University of Michigan, Ann Arbor, MI
Medical Degree:
University of Pittsburgh, School of Medicine, Pittsburgh, PA
Residency:
Junior Medical Resident, Montefiore Hospital Medical Center, Einstein College of Medicine, Bronx, NY
Senior and Chief Medical Resident, Montefiore Hospital Medical Center, Einstein College of Medicine, Bronx, NY
Fellowship:
Infectious Disease, University of New Mexico School of Medicine
Certification:
National Board of Medical Examiners
Diplomate, American Board of Internal Medicine
Diplomate, American Board of Internal Medicine
Contact
Information:
Mailing Address:
The Mucosal Biology Research Center
20 Penn Street, HSFII Rm. 351
Baltimore, MD 21201
Email:
sgoldblu@medicine.umaryland.edu
Phone:
410-706-5504
Fax:
410-706-5508
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 constituent(e.g.: lipopolysaccharide or endotoxin, staphylococcal enterotoxin B) and members of a family of novel counteradhesive proteins (e.g.: 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.
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.
Sui X, Kiser TD, Hyun SW, Angelini DJ, Del Vecchio RL, Young BA, Hasday JD, Romer LH, Passaniti A, Tonks NK, and Goldblum SE. Receptor Protein Tyrosine Phosphatase m Regulates the Paracellular Pathway in Human Lung Microvascular Endothelia. Am J Pathol 2005;166:1247-1258.
Angelini DJ, Hasday JD, Goldblum SE, and Bannerman DD. Tumor necrosis factor-a-mediated pulmonary endothelial barrier dysfunction. Curr Respir Med Rev 2005; 1:233-246.
Lillehoj E, Lu W, Kiser T, Goldblum SE, Kim C. MUC1 inhibits cell proliferation by a beta-catenin-dependent mechanism. Biochimica et Biophsica Acta 2007; 1773:1028-1038.
Kalakonda S, Nallar SC, Gong P, Lindner DJ, Goldblum SE, Reddy SP and Kalvakolanu DV. Tumor Suppressive Protein Gene Associated with Retinoid-Interferon-Induced Mortality (GRIM)-19 Inhibits src-Induced Oncogenic Transformation at Multiple Levels. Am J Pathol 2007; 171:1353-1368.
Gong P, Angelini DJ, Yang S, Xia G, Cross AS, Mann D, Bannerman DD, Vogel SN, Goldblum SE. Toll-like receptor 4 signaling is coupled to src family kinase activation, tyrosine phosphorylation of zonula adherens proteins, and opening of the paracellular pathway in human lung microvascular endothelia. J Biol Chem 2008; 283:13437-13449.
