DEPARTMENT OF VISION SCIENCES
Marina Gorbatyuk, Ph.D.
Office (205) 934.6762
Volker Hall room 443A
1670 University Blvd
1720 2nd Avenue South, VH 443A
Birmingham, AL 35294-0019
PhD, Russian Institute of Biotechnology, Moscow, Russia, Biotechnology
MS, Kazan State University, Russia, Microbiology
BS, Kazan State University, Russia, Microbiology
Vision Science Graduate Program Admissions and Advisory Committee
Vision Science Research Center Advisory Committee
Associate Professor, Department of Neurobiology, UAB
Scientist, Vision Science Research Center
Senior Scientist, Civitan International Research Center
Research: Mechanisms of Retinal Degeneration and Search for Neuroprotective Strategies
My research is concentrated on the elucidation of the role of the Unfolded Protein Response (UPR) in autosomal dominant retinitis pigmentosa (ADRP) pathogenesis and development of the gene therapy based on modulation of the UPR signaling markers. In particular, my lab concentrates on the study of misfolded rhodopsin that interferes with the trafficking of wild-type rhodopsin, accumulates in the endoplasmic reticulum (ER) and stimulates a signal transduction cascade known as the Unfolded Protein Response (UPR). If unchecked, this pathway triggers photoreceptor death, presumably through apoptosis. Therefore, the main focus of my research is to determine whether the gene therapy based on the re-programming of the ER stress response caused by aberrant rhodopsin is a viable treatment and is unlimited by different localizations of rhodopsin mutations. In my current study I use genetic, biochemical, cell biological, physiological and morphometric approaches to dissect mechanisms of retinal degeneration and target the ER stress signaling to restore the photoreceptor cell homeostasis and balance in mouse ADRP models. I am specifically interested in therapeutic targeting of upstream (BiP/GRP78) and downstream (CHOP and caspase-7 and -12) branches of the UPR. Our studies to date indicate that over-expression of BiP protein in ADRP rat’s photoreceptors restores visual function. We have demonstrated that BiP chaperone reprograms the UPR favoring the survival of photoreceptors, blocks apoptosis, and, ultimately, preserves vision. We also have shown that this therapeutic effect is due to reduction of pro-apoptotic CHOP protein and photoreceptor apoptosis. We have detected complexes between BiP, caspase-12, and the BH3-only protein BiK that may contribute to the antiapoptotic activity of BiP. Therefore, reprogramming the upstream (BiP protein) and downstream (CHOP and Caspase-12) branches of the UPR in the same mouse model gives me opportunity to validate the UPR as a possible target for ADRP gene therapy.
Gorbatyuk, M.S., Knox, T, LaVail, MM, Gorbatyuk, OS, Noorwez,S M, Hauswirth, WW, Lin, JH, Muzyczka, N. and Lewin, AS. Restoration of Visual Function in P23H Rhodopsin Transgenic Rats by Gene Delivery of BiP/Grp78. (2010) PNAS 107:5961-6. PMID: 20231467.
Gorbatyuk, OS, Li. S, Nash, K, Gorbatyuk, M, Lewin, AS, Sullivan LF, Mandel, RJ, Chen, Meyers, CW, Manfredsson FP., and Muzyczka, N., In Vivo RNAi-Mediated α-Synuclein Silencing Induces Nigrostriatal Degeneration, Mol Ther. (2010); doi:10.1038/mt.2010.115.
Haoyu Mao, Thomas James, Alison Schwein, Arseniy E. Shabashvili, William W. Hauswirth, Marina S. Gorbatyuk and Alfred S. Lewin “Adeno-associated viral delivery of wild-type rhodopsin gene rescues vision in mice carrying mutated rhodopsin”. Hum Gene Ther. 2011 May;22(5):567-75.
Gorbatyuk M, Shabashvili A., Chen W, Meyers G, Sullivan L., Lin J., Lewin A., Muzyczka N. and Gorbatyuk O. “Glucose regulated protein 78 GRP78/BiP) meliorates alpha-synuclein (α-syn) neurotoxicity in a rat model of Parkinson disease". Molecular Therapy, Mar.2012
Mao H, Gorbatyuk M., Rossmiller B., Hauswirth W., and Lewin A. “Long Term Rescue of Retinal Structure and Function By Rhodopsin RNA Replacement With a Single AAV Vector in P23H RHO Transgenic Mice.” Hum Gene Ther. Mar 28. 2012.
Shinde V., Sizova O., Lin J., LaVail M. and Gorbatyuk M. “ER stress in retinal degeneration in S334ter Rho rats”. PloS One; 7(3) 2012.
Deng WT., Dinculescu A., Li Q., Boye S., Li J., Gorbatyuk M., Pang J-j., Chiodo V., Liu L., Alkuraya F., Zhang K., Vollrath D., LaVail M., Hauswirth W. “Tyrosine-mutant AAV8 delivery of human MERTK provides long-term retinal preservation in RCS Rats”. IOVS, April 6; 53, 2012.