- ASSISTANT PROFESSOR Neuroscience
My overall research goal is to understand the mechanisms of synaptic plasticity and remodeling in the nervous system and the role of these processes in neurodegenerative disorders. I use electrophysiological techniques for recording of neural activity in vivo, in brain slice preparations in vitro, from co-cultured explants, and from dissociated neuronal cultures, as well as collaborative methods including biochemical, molecular biological, and imaging techniques. My model system has primarily been the hippocampus, which is unique in that it appears to mediate information flow between a variety of different sensory inputs and the cortex, and is an area of the brain that plays an important role in learning and memory. Changes in hippocampal function appear to be critical in the cognitive impairment observed in neurodegenerative and neuropsychiatric illnesses. Long-term potentiation, which is viewed as a synaptic model of memory, is one example of how synaptic connections can be altered by neural activity. There are a number of proteins that may directly modify synaptic function and structure, and affect long-term change. My previous work characterized the role of the cell adhesion molecule N-cadherin and degradation of extracellular matrix by MMP-9, in synaptic plasticity and remodeling.
Disruptions in synaptic plasticity and mutations in number of synaptic proteins have long been linked to various neuropsychiatric disorders including autism and related disorders. My ongoing projects are on the mouse models that reflect these genetic alterations implicated in autism and schizophrenia, which may help to understand the pathogenesis of these disorders. One of them is a model with a reduced expression of a synaptic scaffolding protein Shank3, which is a critical part of the core of the postsynaptic density. Haploinsufficiency of the protein causes Phelan-McDermid Syndrome, which is strongly associated with autism. Another one is a mouse model with reduced expression of Cyfip1, which is a Fmrp binding protein, the latter that functions in translational control and the deficiency of the protein causes Fragile X Syndrome. My focus here is to understand the changes in synaptic plasticity and cellular mechanisms of learning and memory in these disorders, identify the deficits in multiple common/different pathways, target proteins, which may contribute to the pathophysiology of autism and related disorders, and then to attempt interventions in the model systems.
Bozdagi O, Wang XB, Nikitczuk J, Anderson T, Radice G, Zhou Q, Benson D, Huntley GW. Persistence of coordinated LTP and dendritic spine enlargement at mature synapses requires N-cadherin. J Neurosci 2010 Jul; 30(30): 9984-9989.
Huntley GW, Elste A, Patil SB, Bozdagi O, Benson DL, Steward O. Synaptic loss and retention of different classic cadherins with LTP-associated synaptic structural remodeling in vivo. Hippocampus 2010 Sep; 16.
Sebeo J, Hsiao K, Bozdagi O, Dimitriu D, Ge Y, Zhou Q, Benson DL. Requirement for Protein Synthesis at Developing Synapses. J Neurosci 2009 Aug; 29(31): 9778-9793.
Wang XB, Bozdagi O, Nikitczuk JS, Zhai ZW, Zhou Q, Huntley GW, . Extracellular proteolysis by matrix metalloproteinase-9 drives dendritic spine enlargement and long-term potentiation coordinately. Proc Natl Acad Sci U S A 2008 Dec; 105(49): 19520-19525.
Bozdagi O, Rich E, Tronel S, Sadahiro M, Patterson K, Shapiro ML, Alberini CM, Huntley GW, Salton SR. The neurotrophin-inducible gene Vgf regulates hippocampal function and behavior through a brain-derived neurotrophic factor-dependent mechanism. J Neurosci 2008 Sep; 28(39): 9857-9869.
Bozdagi O, Nagy V, Kimberly K, Huntley GW. In vivo roles for matrix metalloproteinase-9 in mature hippocampal synaptic physiology and plasticity. J. Neurophysiology 2007 Jul; 98(1): 334-344.
Nagy V, Bozdagi O, Matynia A, Balcerzyk M, Okulski P, Dzwonek J, Costa RM, Silva A, Kaczmarek L, Huntley GW. Matrix Metalloproteinase-9 Is Required for Hippocampal Late-Phase Long-Term Potentiation and Memory. J. Neurosci. 2006; 26(7): 1923-1934.
Bozdagi O, Valcin M, Poskanzer K, Tanaka H, Benson DL. Time-dependent roles for classic cadherins in synapse formation and maturation. Mol. Cell. Neurosci 2004; 27(4): 509-521.
Lilliehook C, Bozdagi O, Yao Y, Gomez M, Pastorino L, Zaidi N, Wasco W, Gandy S, Santucci A, Haroutunian V, Huntley GW, Buxbaum JD. Altered Aß formation and long-term potentiation. J. Neurosci 2003; 23(27): 9097-9106.
Bozdagi O, Shan WS, Tanaka H, Benson DL, Huntley GW. Increasing numbers of synaptic puncta during late-phase LTP: N-cadherin is synthesized, recruited to synaptic sites and required for potentiation. Neuron 2000; 28: 245-259.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr. Gunal did not report having any of the following types of financial relationships with industry during 2015 and/or 2016: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.
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