Stem Cell Center, Yale: Stem Cells and Tissue Repair | Tissue Specific Stem Cells
Our research addresses three interrelated problems in immunobiology and vascular biology. First, we examine and analyze the consequences that ensue when human T lymphocytes recognize specific antigens presented by human vascular cells compared to recognition of antigens presented by professional antigen presenting cells or by tissue cells. Second, we examine signaling pathways and transcriptional regulation of inducible molecules, such as leukocyte adhesion molecules, in vascular cells activated by T cells or their products (e.g., cytokines). Third, we analyze pathways of cell injury in vascular cells caused by leukocytes and their products as well as responses to resist such injuries. These studies may lead to novel, vascular cell-directed therapies for modifying immune and inflammatory diseases and for improved outcomes in transplantation of organs or tissue-engineered grafts.
Extensive Research Description
Our research addresses three interrelated problems in the immunobiology and pathology of vascular endothelial cells. First, we examine and analyze the consequences that ensue when human T lymphocytes recognize specific antigens presented by human vascular endothelial cells, pericytes or smooth muscle cells in comparison to recognition of antigens presented by professional antigen presenting cells or by tissue cells (e.g., fibroblasts).
Second, we examine the signaling pathways activated by T cells or their products (e.g., cytokines) or by B cell products (e.g., antibodies) and the transcriptional regulation of cytokine-induced molecules, such as leukocyte adhesion molecules, within vascular endothelial cells. We also study how these signals differentially affect various segements of the vascular tree such as arteries, capillaries or post-capillary venules. Third, we analyze the pathways of cell injury (e.g., apoptosis) in vascular endothelial cells induced by leukocytes and their products as well as responses made by endothelial cells to resist such injury.
Our experimental approaches involve use of normal and genetically-modified (i.e., transfected) cell populations in culture, use of chimeric animals, (e.g., immunodeficient mice doubly engrafted with human blood vessels and with human lymphocytes), and use of discarded human tissues from control and disease settings. These studies may lead to novel, vascular cell-directed therapies for modifying immune and inflammatory diseases. A particular focus of our work is on modifying the behavior of endothelial cells to improve outcomes of clinical transplantation and tissue engineering.
- Devalliere J, Chang WG, Andrejecsk JW, Abrahimi P, Cheng CJ, Jane-wit D, Saltzman WM, Pober JS. Sustained delivery of proangiogenic microRNA-132 by nanoparticle transfection improves endothelial cell transplantation. FASEB J 2014; 28:908-22.
- Jane-wit D, Manes TD, Yi T, Qin L, Clark P, Kirkiles-Smith NC, Abrahimi P, Devalliere J, Moeckel G, Kulkarni S, Tellides G and Pober JS. Alloantibody and complement promote T cell-mediated cardiac allograft vasculopathy through non-canonical nuclear facto
- Neutralizing IL-6 reduces human arterial allograft rejection by allowing emergence of CD161+ CD4+ regulatory T cells. Fogal B, Yi T, Wang C, Rao DA, Lebastchi A, Kulkarni S, Tellides G, Pober JS. J Immunol. 2011 Dec 15;187(12):6268-80. Epub 2011 Nov 14.
- Enis DR, Shepherd BR, Wang Y, Qasim A, Shanahan CM, Weissberg PL, Kashgarian M, Pober JS, Schechner JS. Induction, differentiation and remodeling of mature blood vessels after transplantation of Bcl-2-transduced endothelial cells. Proc Natl Acad Sci.
- Tellides G, Tereb DA, Kirkiles-Smith NC, Kim RW, Wilson JH, Schechner JS, Lorber MI, Pober JS. Interferon-? elicits arteriosclerosis in the absence of leukocytes. Nature. 2000; 403:207-211.