- Attending, Division of Infectious Diseases
- Chief, Infectious Disease Section, VA Maryland Health Care System
- Associate Director of Basic Science, The Mucosal Biology Research Center,
University of Maryland School of Medicine
Current Research Interest:
- Host Responses to Infectious Diseases
- Interleukin-1, Tumor Necrosis Factor
- Endothelial Barrier Function
- Endothelial Cytoskeletal Organization
- LPS Presentation to Host Target Tissues
- Counteradhesive Proteins (SPARC/osteonectin, Thrombospondin-1)
- Protein Tyrosine Phosphorylation signaling events
- Intercellular Junctions (zonula adherens)
- Zonula Occludins Toxin
- Transendothelial Migration of Leukocytes
- Sialidases
- Angiogenesis
Our laboratory is interested in the intracellular effector mechanisms that
couple specific receptor-ligand interactions with opening of the pulmonary vascular
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 receptor and nonreceptor
protein tyrosine phosphatases (PTPs) that associate with and restrain tyrosine
phosphorylation of zonula adherens proteins with a focus on ZA-associated PTPs
including PTPm.
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.
Current Research Funding:
- 1999-2004 National Institutes of Health: "Thrombospondin-1 opens endothelial
paracellular pathway." R01 HL63217
- 2002-2007 National Institutes of Health: "PTPm regulates lung endothelial
paracellular pathway". R01 70155-01
- 1999-2004 National Institutes of Health: "Regulation of tight junctions
and role in diarrhea". R01 DK48373
- 2002-2004 American Heart Association: "TNFa regulates the pulmonary
endothelial paracellular pathway through protein tyrosine phosphorylation
- 2003-2008 National Institutes of Health: "PTPm regulates cytoskeleton-driven
angiogenesis". NIH P01 HL58064
- 2003-2008 National Institutes of Health: "Lung vascular barrier preservation
by platelet products." NIH P01 HL58064
- 2003-2008 National Institutes of Health: "Mechanisms of fever-enhanced
hyperoxic lung injury."
Education:
- MD - University of Pittsburgh School of Medicine, (1973)
- House Staff Training: Montefiore Hospital Medical Center; Einstein College
of Medicine
- Fellowship Training: University of New Mexico School of Medicine
Simeon
E.
Goldblum, M.D. 