Martin S Kluger PhD

Research Scientist in Immunobiology

Research Interests

Vascular Hyperpermeability (leak); Angiogenesis/Lymphangiogenesis; Tumor Necrosis Factor (TNF); Vascular Endothelial Growth Factor (VEGF); Tissue edema; synthetic engineered tissues; microvascular endothelial cells; pericytes

Current Projects

1. Molecular mechanisms of tumor necrosis factor-induced vascular leak.
2. Pericyte-induced stabilization of neo-microvessels formed in collagen-fibronectin matrices: Potential applications to biomedical engineering.

Research Summary

Endothelial cells form an inner lining to human microvessels that serve as a systemic organ for regulating the access of fluid, macromolecules and cells from circulating blood into all vascularized tissues. We focus on how to maintain stable endothelial cell-cell junctions during activation by inflammatory mediators (cytokines). This is important to systemic sepsis, atherosclerosis and ischemia reperfusion injury. We are also interested in how endothelial cells and pericytes form new microvessels (angiogenesis). This process is relevant to wound healing, to tumor (lymph)angiogenesis and to the engineering of vascularized synthetic tissues.

Extensive Research Description

We are defining how the inflammatory cytokine tumor necrosis factor (TNF) destabilizes blood vessel barrier integrity by increasing their paracellular permeability to fluid and (macro)molecules in circulating blood. We study how transmembrane adhesion molecules found at cell-cell junctions (such as claudin-5, JAM-A, occludin and VE-cadherin) regulate paracellular permeability by knocking down and overexpressing these genes in cultured primary human endothelial cells (EC). A second research goal with applications to biomedical engineering of replacement organs is in defining how nascent microvessels become stabilized when EC interact with accessory cells (pericytes) during angiogenesis. In this work, we explore the molecular mechanisms of microvascular tube formation by EC and pericytes in 3-D collagen/fibronectin matrices.

Selected Publications

  • *Kluger MS, Clark PR, Tellides G, Gerke V, Pober JS. 2013. Claudin-5 Controls Intercellular Barriers of Human Dermal Microvascular but not Human Umbilical Vein Endothelial Cells. Arteriosclerosis, Thrombosis, and Vascular Biology 33:489-500 http://atvb.ahajournals.org/content/early/2013/01/03/ATVBAHA.112.300893.abstract.html?ijkey=BRkjvG2zQUoMVTj&keytype=ref *Faculty of 1000 Recommended: Access the recommendation on F1000Prime
  • Clark, P.R., Manes, T.D., Pober, J.S. and Kluger, M.S. Increased ICAM-1 expression causes endothelial cell leakiness, cytoskeletal reorganization and junctional alterations. Journal of Investigative Dermatology. 2007. 127: 762-774.
  • *D’Alessio, A., * Kluger, M.S (*co-First Author), Li, J.H., Al-Lamki, R., Bradley, J.R., and Pober. J.S. Targeting of Tumor Necrosis Factor Receptor 1 to Low Density Plasma Membrane Domains in Human Endothelial Cells. Journal of Biological Chemistry. 2010. 285(31) 23868-23879
  • Jones, D., Xu, Z., He Y., Li, S., Shibo T., Kluger, M.S., Alitalo. K., Chen, H. and Min, W. A critical role for Bmx in pathological lymphangiogenesis and tumor metastasis. Arteriosclerosis, Thrombosis, and Vascular Biology. In Press.

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