Department of Psychiatry Faculty

Angus Nairn , PhD Professor of Psychiatry CMHC, 34 Park Street Tel: 203-974-7725 Fax: 203-974-7724 Email: angus.nairn@yale.edu

Education

1979, Ph.D, University of Birmingham, England

Research Interest

Our research is focused on the molecular actions of dopamine in the basal ganglia. The disruption of normal dopaminergic neurotransmission is known to underlie certain neurological diseases, including Huntington's and Parkinson's disease, schizophrenia and attention deficit hyperactivity disorder. Modulation of dopamine-regulated signaling pathways is also likely to play an important role in the addictive actions of various drugs of abuse. Our studies of basal ganglia phosphoproteins, particularly DARPP-32, RCS (Regulator of calmodulin signaling) and ARPP-16, will hopefully provide incites into how dopaminergic neurotransmission is altered in various diseases models and also to provide a rational new approach to developing drugs that specifically affect these phosphoproteins or their targets.

Our future studies will continue to focus on the biochemical characterization of DARPP-32 and its target, the multifunctional serine/threonine protein phosphatase, PP1, as well as on substrates and other regulators of PP1. We will also examine the functional role of PP1 utilizing mice models deficient in various PP1 isoforms. Other studies will examine the role of the regulatory proteins, RCS and ARPP-16 using mice models deficient in these proteins. We have recently helped established the Yale/NIDA Neuroproteomics and our future studies will utilize state-of-the-art proteomics techniques to investigate the role of DARPP-32, RCS and ARPP-16 in dopaminergic neurotransmission.

Area of Expertise

Dopaminergic signal transduction and the structure and function of protein kinases and phosphatases.

Laboratory Personnel

Christian Collin-Hansen, Postdoc Associate
Dilja Kruger, Maya Davis, and Erika Andrade, PhD, students

Achievements and Honors

• Fellowship for research in Japan, University of Nagoya, from the Japan Society for the Promotion of Science (1992)

• Editorial Board of the Journal of Biological Chemistry (1993-97)

• Editor of Advances in Second Messenger and Phosphoprotein Research

• Associate Editor of Journal of General Physiology

• Organizer FASEB 2004 Summer Conference on Protein Phosphatases.

Publications of Note

Rakhilin, S.V., Olson, P.A., Nishi, A., Starkova, N.N., Fienberg, A.A., Nairn, A.C., Surmeier, D.J., Greengard, P. (2004) A novel regulator of calmodulin-dependent signaling. Science 306:698-701.

Svenningsson, P., Nishi, A., Fisone, G., Girault, J.-A., Nairn, A.C. and Greengard, P. (2004) DARPP-32-an integrator of neurotransmission in striatal neurons. Ann. Rev. Pharmacol.44:269-296.

Williams, K., Wu, T., Colangelo, C., Nairn. A.C. (2004) Recent Advances in Neuroproteomics and potential application to studies of drug addiction. Neuropharmacology. 47S1:148-166.

Nairn, A.C., Svenningsson, P., Nishi, A., Fisone, G., Girault, J.-A and Greengard, P. (2004) The role of DARPP-32 in the actions of drugs of abuse. Neuropharmacology. 47S1: 14-23.

Valjent, E., Pascoli, V., Svenningson, P., Paul, S., Enslen, H., Corvol, J.C., Stipanovich, A., Caboche, J., Lombroso. P., Nairn, A.C., Greengard, P., Hervé, D. and Girault, J.A. (2005) Regulation of a protein phosphatase cascade allows convergent dopamine and glutamate signals to activate ERK in the striatum. Proc. Natl. Acad. Sci. USA. 102:491-496.

Futter, M., Uematsu, K., Bullock, S.A., Kim, Y., Hemmings Jr., H.C. Nishi, A., Greengard, P., and Nairn, A.C. (2005) Phosphorylation of spinophilin by ERK and Cdk5. Proc. Natl. Acad. Sci. USA. 102:3489-3494.

Ryan, X.P., Alldritt, J., Wu, G.-Y., Allen, P., Nairn, A.C. and Greengard, P. (2005) The rho-specific GEF, Lfc, interacts with neurabin and spinophilin to regulate dendritic spine morphology. Neuron 47:85-100.

Rosenberg, O.S., Deindl, S., Sung, R.-J., Nairn, A.C. and Kuriyan, J. (2005) Crystal structure of the auto-inhibited kinase domain of Ca2+/Calmodulin-dependent kinase II and SAXS analysis of holoenyzme assembly. Cell. 123:849-860.

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