This application is for an ADAMHA RSDA, Level I. My nominating institution is the New York University Medical Center. My training and research will take place at Rockefeller University. Clinical material will come from The Karolinska Institute. The proposed research will examine the potential role of neuronal protein phosphorylation in the pathophysiology of neuropsychiatric disorders, with a particular emphasis on schizophrenia. Over 70 neuron-specific phosphoproteins recently have been described in the central nervous system. Some of these phosphoproteins are specifically located in the basal ganglia or limbic system, sites of particular relevance to neuropsychiatric disorders. The phosphoproteins have an important potential role as a common final pathway for both endogenous (e.g., neurotransmitters) and exogenous (e.g., psychoactive drugs) neuroregulatory agents. The development of assays for these phosphoproteins in human brain and CSF, and the description of their presence, character and quantity in normal and abnormal tissue are the major areas for this proposed research. My research development will occur through formal and informal instruction in biochemistry, collaboration with both basic scientists and clinicians,and work in the laboratory. My training in research currently includes extensive experience in clinical and animal studies at UCSF and the NIMH Neuropsychiatry Branch. I will have been at Rockefeller 1 1/2 years at the time when this requested RSDA support could begin. An RSDA would allow me to integrate solidly the skills for basic research in the neurosciences with clinical aspects of major mental disorders. My professional growth plans include a translocation of my research activities from Rockefeller to an independent laboratory at NYU during the fifth year of this proposed research plan. Dr. Arnold Friedhoff, as well as the facilities of the Milhauser Laboratories at NYU, would be available to me at that time. I would continue, of course, a close collaboration with Dr. Greengard. During years 3-5 of this grant period, I plan to submit RO-1 applications that would involve the facilities, faculty and clinical populations of the NYU Department of Psychiatry. My eventual career goal is to coordinate a schizophrenia research group that would be involved in basic, animal and human research.
| Nordstedt, C; Gandy, S E; Alafuzoff, I et al. (1991) Alzheimer beta/A4 amyloid precursor protein in human brain: aging-associated increases in holoprotein and in a proteolytic fragment. Proc Natl Acad Sci U S A 88:8910-4 |
| Grebb, J A; Greengard, P (1990) An analysis of synapsin II, a neuronal phosphoprotein, in postmortem brain tissue from alcoholic and neuropsychiatrically ill adults and medically ill children and young adults. Arch Gen Psychiatry 47:1149-56 |
| Grebb, J A; Girault, J A; Ehrlich, M et al. (1990) Chronic treatment of rats with SCH-23390 or raclopride does not affect the concentrations of DARPP-32 or its mRNA in dopamine-innervated brain regions. J Neurochem 55:204-7 |
| Grebb, J A; Browning, M D; Valverius, P et al. (1989) An analysis of postmortem brain samples from 32 alcoholic and nonalcoholic individuals for protein III, a neuronal phosphoprotein. Alcohol Clin Exp Res 13:673-9 |
