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Clinical Associate Professor Department of Pathology Division of Surgical and Neuropathology Office location: BSB 4-113 Tel: (718) 270- 6755 Fax: (718) 270-3313 e-mail: charles.shao@downstate.edu
Research Interest Summary I am interested in the pathogenesis of neurodegenerative diseases, especially Alzheimer’s Disease (AD) the most common form of memory disorders. Accumulating evidence has indicated that synaptic plasticity such as long-term potentiation (LTP) that underlines learning and memory is impaired in AD. I currently focus on an unique molecule called PKMzeta that plays a critical role in LTP maintenance and memory function in living animals. I have found that PKMzeta associates with a variety of AD pathology that mark changes of postsynaptic structures such as Hirano bodies (dendritic spines), perisomatic granules (AMPA receptors) and granulovacular degeneration. I postulate that PKMzeta regulate these structures during memory formation and their aggregation during AD lead to memory loss. Using primary cultures of hippocampal neurons, I demonstrate that PKMzeta indeed positively regulates synaptic structures and AMPA receptors. Further studies will explore what alters PKMzeta in neurons and how PKMzeta may play a role in combating AD.
PKMzeta in AD hippocampal pathology. a. Hirano body (HB). b. Granulovacuolar degeneration (GVD). c. Perisomatic granules (PSG) are immunoreactive for anti-GluR2 antibody. d-f. PKMzeta immunoreactivity in HB, GVD and PSG.
Selected Publications Shao, C.Y., R. Sondhi, T.C. Sacktor, PKMzeta regulates PSD-95 and AMPA receptor trafficking in hippocampal neurons. 2007 Society for Neuroscience. Abstract. Shao, Charles Y., Rachna Sondhi, William Oxberry, Matthew T. Kelly, Suzanne . Mirra, Todd C. Sacktor. Protein kinase M zeta regulates AMPA receptors on hippocampal neurons linking long term synaptic plasticity to Alzheiemr’s disease. Brain Pathology 2006; 16:s159 Shao CY, Crary JF, Rao C, Sacktor TC, Mirra SS. Atypical Protein Kinase C in Neurodegenerative Disease II: PKCi/l in Tauopathies and a-Synucleinopathies. J. Neuropath. Exp. Neurol. 2006; 65:327-335. Crary JF*, Shao CY*, Mirra SS, Hernandez AI, Sacktor TC. Atypical Protein Kinase C in Neurodegenerative Disease I: PKMzeta Aggregates with Limbic Neurofibrillary Tangles and AMPA Receptors in Alzheimer’s Disease. J. Neuropath. Exp. Neurol. 2006; 65:319-326. *equal contributions Shao, Y., M. Gearing, and S. S. Mirra. Astrocyte-apolipoprotein E (apoE) associations in senile plaques in Alzheimer’s disease and vascular lesions: A regional immunohistochemical study. J. Neuropath. Exp. Neurol. 1997; 56:376-381. Shao, Y. and K.D. McCarthy Responses of Bergmann glia and granule neurons in situ to N-methyl-D-aspartate, norepinephrine and high potassium: Implication of neuron-glia interaction. J. Neurochemistry 1997; 68:2405-2411 Shao, Y. and K.D. McCarthy Receptor-mediated calcium signals in astroglia: Multiple receptors, common stores and all-or-nothing responses. Cell Calcium 1995; 17:187-196
Education and Training 1983.M.D., Capital University of Medical Science, Beijing, China. 1985-1990. Ph.D., Emory University School of Medicine, Atlanta, GA 1990-1995. Postdoc. University of North Carolina at Chapel Hill, NC 1995-1997. Alzheimer’s Disease Center, Emory University School of Medicine. 1997-2001. Resident/Fellow, AP/NP, Department of Pathology, New York University Medical Center, NY
Committees , Council, and Professional Society Memberships American Association of Neuropathologists, 2002-present American Medical Association, 1998-present College of American Pathologists, 1997-present Society for Neuroscience, 1985-1997, 2002-present
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