Martin S. Kluger, PhD

Research Scientist, Department of Dermatology, Program in Vascular Biology and Therapeutics

Director, Endothelial Cell Culture Core, Yale Skin Disease Research Center

Director, Yale School of Medicine Dermatology Scientific Lecture Series

Curriculum Vitae

Research Interests

1. How vascular hyperpermeability occurs in skin cancer
2. Recruitment of circulating tumor cells or leukocytes from blood by adhesion molecules and chemokines on the endothelial cell surface

Research Program

We are using human skin and human skin-derived endothelial cells to study vascular hyperpermeability (leak) in skin cancer (melanoma). Endothelial cells form an inner lining to human blood vessels and serve as a homeostatic organ by regulating passage of blood proteins into all vascularized bodily tissues. Under normal physiological conditions quiescent endothelium is selectively impermeable to blood macromolecules. But in tumor proximal vessels endothelium becomes activated by tumor-derived vascular endothelial growth factor (VEGF-A) and other factors, resulting in vascular hyperpermeability to blood macromolecules. Importantly, vascular hyperpermeability correlates with tumor progression and with metastasis, but the mechanism(s) by which tumors induce endothelial cell hyperpermeability are not well understood.

We use two different experimental models for studying human endothelial barrier function in skin cancer. In our in vivo model, we sub-cutaneously inject human melanoma cells beneath human skin grafted onto immunodeficient SCID mice. In this model, VEGF derived from melanoma cells is both required and sufficient for inducing vascular leak in skin grafts, and antibody blockade of VEGF inhibits tumor progression. In our in vitro model, VEGF is also required for triggering vascular leak across monolayers of human dermal microvascular endothelial cells (HDMEC). In this model we found that melanoma factors other than VEGF induce endothelial synthesis and activation of matrix metalloproteinases that increase vascular leak.

We are also interested in how adhesion molecules and chemokines expressed on the endothelial surface may regulate recruitment (adhesion and transendothelial migration) of circulating tumor cells in blood, a key step in melanoma metastasis from skin to distal organs. Previously, we found that transducing HDMEC to over express intercellular adhesion molecule-1 (ICAM-1) and overlaying chemokines such as SDF-1 and IP-10 on the HDMEC surface suffices for CD4+ memory T cell adhesion and transendothelial migration. We are now interested in whether similar interactions may underlie recruitment of blood born tumor cells such as metastasizing melanoma cells originating in skin.

Education:	BA, Magna cum Laude, Yale University, MS, Biochemistry, University of Connecticut PhD, Biochemistry, University of Connecticut
Training:	Training: Dermatology and Immunobiology, Yale School of Medicine

Contact

Academic Office
Yale School of Medicine
Amistad Research Building
10 Amistad Street, Room 401A New Haven, CT 06520
(203) 737-2870

E-mail
martin.kluger@yale.edu