Research
The current interest of the group is to develop the best approach for generation of non- immunogenic tissue patches suitable for repair of damaged myocardium. Stem cell-derived cardiomyocytes are essential but not sufficient part of such constructs therefore we are concentrating on generation of non-immunogenic fibroblast and eventually endothelial cells. The ultimate goal of our current studies is to test survival of those cells in the context of re-cellularized cardiac scaffolds within allogeneic and xenogeneic hosts. This project requires expertise in stem cell biology, immunology and cardiac pathophysiology. Dr. Karabekian, the principle investigator of the group, received graduate training in immunology (Eastern Virginia Medical School), during which she published a number of manuscripts in the area of host-virus interactions. She then continued in the immunology field with post-doctoral training at the National Eye Institute (NIH) working on the mechanisms of autoimmune uveitis, and T-cell recognition and tracking. The second post-doctoral training was at the Department of Pharmacology and Physiology in Dr. Sarvazyan’s laboratory (George Washington University). This recent Dr. Karabekian’s training resulted in knowledge in the area of cardiac physiology and expertise in stem cell biology. Dr. Karabekian developed and characterized a new line of embryonic stem cells that overexpress an adhesion protein, which can potentially improve cardiac engraftment. In December 2009, she was promoted to Research Assistant Professor in the same department. The group is also presently working on generation of yet another embryonic stem cell line that is capable of direct differentiation into stem cell-derived cardiomyocytes with reduced immunogenicity. The ongoing project is multidisciplinary, and as such, provides ample opportunities for a student to develop a scientific approach and utilize fundamental molecular biology techniques related to stem cell biology and tissue regeneration. If proven to be successful, the proposed strategy will be used to produce a universal donor cell population for use in other tissue types.
- Karabekian Z., Gillum N., and Sarvazyan N. Immunological barriers to stem-cell based cardiac repair. Stem Cell Reviews and Reports, 2011, Jun;7(2):315-25
- Mattapallil MJ, Silver PB, Mattapallil JJ, Horai R, Karabekian Z, McDowell JH, Chan CC, James EA, Kwok WW, Sen HN, Nussenblatt RB, David CS, Caspi RR. Uveitis-associated epitopes of retinal antigens are pathogenic in the humanized mouse model of uveitis and identify autoaggressive T cells. J Immunol. 2011 Aug 15;187(4):1977-85.
- Karabekian Z., Gillum N., Wong E., and Sarvazyan N. Effects of N-cadherin overexpression on adhesion properties of embryonic stem cells. 2009, Cell Adhesion and Migration, Vol.3, 305-10.
- Gillum N., Karabekian Z., Swift L., Brown R., Kay M., and Sarvazyan N. Clinically relevant concentrations of Di (2-ethylhexyl) phthalate (DEHP) uncouple cardiac syncytium. 2009. Toxicology and Applied Pharmacology, Vol. 236 :25-38
- Barunts K., Gillum N., Karabekian Z., Sarvazyan N. Formation of cardiac fibers in Matrigel matrix. 2008. BioTechniques, Vol. 44. p. 341-8.
- Liang, W., Karabekian, Z., Xu, Q., Viley, A. M. and David W. Scott. B cell delivered gene transfer of human S-Ag Ig fusion protein protects from Experimental Autoimmune Uveitis 2006.Clinical Immunology, Volume 118:35-41.
- Karabekian, Z., Lytton S., Silver P.S., Sergeev Y., Jonathan P. Schneck and Rachel Caspi. Antigen/MHC Class II/Ig Dimers for Study of Uveitogenic T Cells: IRBP p161–180 Presented by both IA and IE Molecules.2005. Investigative Ophthalmology & Visual Science, 46:3769–3776.