Nader Sheibani, Ph.D.
Associate Professor
Clinical Sciences Center, Room K6/458
600 Highland Avenue
Madison, WI 53792-3284
(608) 263-3345
| Degrees: | B.S. 1982, Nasson College, Springvale, Maine M.S. 1985, University of New Hampshire, Durham Ph.D., 1989, University of Nebraska Medical Center, Omaha |
| Appointments: | RRF/Alice R. McPherson Chair Pharmacology, Carbone Comprehensive Cancer Center, Cardiovascular Research Center |
| Fellowships: | Postdoctoral Fellowship, 1989-92, UW- Madison Postdoctoral Fellowship, 1992-96, Washington University School of Medicine, St. Louis Research Assistant Professor, 1996-00, Washington University School of Medicine, St. Louis |
| Specialty: | Dr. Sheibani is a trainer in the Cellular and Molecular Biology, the Cellular and Molecular Pathology, and the Molecular and Environmental Toxicology Graduate Programs. |
| Research: | Diabetic Retinopathy, Retinopathy of Prematurity, Animal Models, Retinal Vascular Cell Biology and Signal Transduction. The growth of new blood vessels from preexisting capillaries (angiogenesis) contributes to the pathogenesis of many diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, the major causes of blindness. Understanding the molecular and cellular mechanisms that regulate angiogenesis and, how their alterations contribute to growth of new blood vessels, has significant clinical impact. Our laboratory has demonstrated that thrombospondin-1 (TSP1), an endogenous inhibitor of angiogenesis, is an important modulator of retinal vascular homeostasis. Mice deficient in TSP1 fail to undergo appropriate vascular pruning and remodeling during postnatal vascularization of the retina; as a result they exhibit increased retinal vascular density. This finding opens many new questions relating to the molecular and signaling mechanisms that mediate TSP1 activity. We have prepared cultures of vascular cells, including endothelial cells (EC), pericytes/smooth muscle cells, and astrocytes from TSP1-/- and wild type mice. A goal of our lab is to determine the role TSP1 plays in coordinating the interactions among these cells during postnatal vascularization of the retina. Gene array analysis of retinal EC, with and without TSP1, has also identified a number of genes whose expression is differentially regulated. We are determining how alterations in the expression of these genes impact retinal EC phenotype and angiogenesis. Similar studies are being performed addressing the function of other angiogenesis related genes including CYP1B1, PECAM-1, endoglin, and members of bcl-2 family of proteins. In separate studies, we have discovered that TSP1 is present at a significantly high level in the vitreous and aqueous humors of normal eyes, but its level is decreased at these sites during diabetes. Therefore, changes in TSP1 levels during diabetes may contribute to the development and progression of diabetic retinopathy. Our current studies indicate that in the absence of TSP1, the development and progression of retinopathies, as well as nephropathies, are significantly exacerbated in a novel diabetic model developed in our laboratory. Utilizing these mice, we are studying how lack of TSP1 exacerbates the development and progression of early diabetic retinopathies and nephropathies. Future studies will focus on the contribution of TSP1 to altered cell adhesive interactions that results in loss of vascular cells, leakiness of blood vessels, hypervascularization of the retina and kidney, and loss of vision and renal function in diabetes. Similar studies are being performed with another endogenous inhibitor of angiogenesis, pigment epithelium derived factor (PEDF). The results of these studies will have great impact not only in understanding the mechanisms which normally keep ocular and renal vasculature in check but also aid in the advancement and design of new therapies to prevent loss of vision and kidney function in diabetes. |
| Publications: | Sheibani N, Scheef EA, DiMiao TA, Kondo S, and Sorenson CM. (2007). Bcl-2 expression modulates cell adhesion and migration promoting branching of ureteric bud cells. J Cell. Physiol 210:616-625. Albert DM, Scheef EA,Wang S, Mehraein F, Sorenson CM, Darjatmoko SR, and Sheibani N. (2007) Calcitriol is a potent inhibitor of retinal neovascularization. Invest. Ophthalmol. Vis. Sci. 48:2327-2334. Kondo S, Scheef EA, Sheibani N, and Sorenson CM. (2007) PECAM-1 isoform-specific regulation of kidney endothelial cell migration and capillary morphogenesis. Am. J. Physiol. Cell. Physiol. 292:C2070-C2083. Scheef EA, Huang Q, Wang S, Sorenson CM, and Sheibani N. (2007). Isolation and characterization of corneal endothelial cells from wild type and thrombospondin-1 deficient mice. Mol. Vision 131:1483-1495. Sheibani N, Tang Y, and Sorenson CM. (2008). Paxillin's LD4 motif interacts with bcl-2. J. Cell. Physiol. 214:655-661. DiMaio TA, and Sheibani N (2008) PECAM-1 Isoform specific functions in PECAM-1-deficient brain microvascular endothelial cells. Microvascular Res. 75:188-201. DiMaio TA, Wang S, Huang Q, Scheef EA, Sorenson CM and Sheibani N (2008) attenuation of retinal vascular development and neovascularization in PECAM-1 deficient mice. Developmental Biol. 315:72-88. Peterson KJ, Sadowsky JD, Scheef EA, Pal S, Kourentzi KD, Willson RC, Bresnick EH, Sheibani N, Gellman S. (2008) A Fluorescence polarization assay for identifying ligands that bind to vascular endothelial growth factor. Analytical Biochem. 378:8-14. Huang Q, Wang S, Sorenson CM, Sheibani N. (2008) PEDF-deficient mice exhibit an enhanced rate of retinal vascular expansion and are more sensitive to hyperoxia-mediated vessel obliteration. Exp. Eye Res. 87:226-241. Kondo S, Tang Y, Scheef EA, Sheibani N, Sorenson CM. (2008) Attenuation of retinal endothelial cell migration and capillary morphogenesis in theaAbsence of bcl-2. Am. J. Physiol. Cell. Physiol. 294:C1521-C1530. Huang Q, Sheibani N. (2008) High glucose promotes retinal endothelial cell migration through activation of Src, PI3K/Akt1/eNOS, and ERKs. Am J Physiol Cell Physiol 295:C1647-C1657. Tang Y, Scheef EA, Wang S, Sorenson CM, Marcus CB, Jefcoate CR, Sheibani N. (2009) CYP1B1 expression promotes the proangiogenic phenotype of endothelium through decreased intracellular oxidative stress and thrombospondin-2 expression. Blood 113:744-754. |