Yaron Rabinowitz, MD
The main focus of the laboratory is to identify susceptibility genes and gene loci for eye diseases and delineate the underlying pathophysiology of the disease process. Ultimately, we hope to develop a cure or therapeutic strategies to prevent progression of the disease. For one disease, Keratoconus, the major cause for corneal transplantation in Western Developed countries, we have identified several gene loci associated with the disease and were the first group to identify a molecular defect in Keratoconus i.e. the suppression of Aquaporin 5. We have also identified new stem cells unique to the cornea and are embarking on a new project to identify genes leading to the development of Keratoconus in the Latino population.
- Rabinowitz YS, Dong L, Wistow G. Gene expression profile studies of the human Keratoconus corneas for NEIbank. A novel cornea expressed gene and the absence of transcripts for Aquaporin 5. Invest Ophthalmol Vis Sci 2005 April 46(4) 1239-46.
- Tang YG1, Rabinowitz YS, Taylor KD, Li X, Hu M, Picornell Y,Yang H. A genome wide linkage scan in a multi-generation Caucasian pedigree identifies a novel susceptibility locus for keratoconus on chromosome 5q14.3-q21.1 Genet Med. 2005 Jul-Aug; 7(6):397-405.
- Li X, Rabinowitz YS, Tang YG, Picornell Y, Taylor KD, Hu M, Yang H. Two-stage genome-wide linkage scan in keratoconus sib pair families.Invest Ophthalmol Vis Sci. 47(9):3791-5, 2006.
Alexander Ljubimov, PhD
Current research in the laboratory is centered on mechanisms of diabetic retinal and corneal disease. Using adenoviral gene therapy we were able to correct aberrant wound healing and several protein expression abnormalities in human organ cultured diabetic corneas by transduction of the c-met gene. Conversely, introduction of specific proteinase genes into normal corneas delayed their wound healing, similar to diabetic ones. We are now applying the combination therapy principle to correct diabetic corneal abnormalities and are investigating ways to apply gene therapy to diabetic corneal epithelial stem cells.
We also study the role of a ubiquitous protein kinase CK2 in retinal angiogenesis and neovascularization. We were the first to show that this enzyme plays an important role in pathologic retinal neovascularization, which could be greatly reduced by CK2 inhibitors. We recently showed that specific CK2 inhibition suppresses engraftment of endothelial progenitor cells into newly formed retinal capillaries in the mouse retinopathy model. This may be a new mechanism of action of antiangiogenic drugs.
- Kramerov AA, Saghizadeh M, Pan H, Kabosova A, Montenarh M, Ahmed K, Penn JS, Chan CK, Hinton DR, Grant MB, Ljubimov AV: Expression of protein kinase CK2 in astroglial cells of normal and neovascularized retina. Am J Pathol, 168(5):1722-36, 2006.
- Xu KP, Li Y, Ljubimov AV, Yu FS: High glucose suppresses epidermal growth factor receptor/phosphatidylinositol 3-kinase/Akt signaling pathway and attenuates corneal epithelial wound healing. Diabetes, 58(5): 1077-85, 2009.
- Saghizadeh M, Kramerov AA, Yu FS, Castro MG, Ljubimov AV: Normalization of wound healing and diabetic markers in organ cultured human diabetic corneas by adenoviral delivery of c-met gene. Invest. Ophthalmol Vis Sci, 51(4): 1970-80, 2010.
Homayon Ghiasi, PhD
Research efforts are directed toward understanding the mechanisms of host resistance and susceptibility to HSV-1 infection with special emphasis on the use of expressed HSV-1 glycoproteins and mutant strains of HSV-1 expressing different cytokine genes; and the immunobiology of antigen presentation, T-cell recognition, and cytokine responses. Current projects include: 1) Improvement of vaccine efficacy against HSV, 2) The role of gK in HSV-1 induced corneal scarring, and 3) The role of IL-2 and HSV-1 in CNS demyelination.
- Mott KR, Underhill D, Wechsler SL, and Ghiasi H: Lymphoid-related CD11c+CD8+ dendritic cells are involved in enhancing HSV-1 latency. J Virol. 82:9870-9879, 2008.
- Mott KR, Bresee CJ, Allen SJ, BenMohamed L, Wechsler SL, and Ghiasi H: Level of HSV-1 latency correlates with severity of corneal scarring and exhaustion of CD8+ T cells in trigeminal ganglia of latently infected mice. J Virol. 83:2246-2254, 2009.
- Zandian M, Belisle R, Mott KR, Nusinowitz S, Hofman FM , and Ghiasi H: Optic neuritis in different strains of mice by a recombinant HSV-1 expressing murine interleukin-2. Invest Ophthalmol Vis Sci, 50:3275-3282, 2009.