Jonathan Javitch, M.D., Ph.D.
Jonathan A. Javitch obtained his B.S. and M.S. in Biological Sciences at Stanford University. He completed the joint M.D.-Ph.D. program at the Johns Hopkins University School of Medicine where as a graduate student with Solomon Snyder he demonstrated that a key step in the neurotoxicity of MPTP is the uptake of its metabolite MPP+ by the dopamine transporter.
After graduating from Hopkins, Dr. Javitch completed a medical internship and psychiatric residency at the Columbia Presbyterian Hospital and the New York State Psychiatric Institute. He did postdoctoral work on the structure of dopamine receptors with Dr. Arthur Karlin at Columbia University.
Dr. Javitch is currently the Lieber Professor of Experimental Therapeutics in Psychiatry and Professor of Pharmacology in the Center for Molecular Recognition and in Physiology and Cellular Biophysics at the Columbia University College of Physicians and Surgeons, Director of the Lieber Center for Schizophrenia Research and Treatment, and Chief of the Division of Molecular Therapeutics at the New York State Psychiatric Institute.
One main line of research in his laboratory is aimed at understanding the structural bases of agonist and antagonist binding and specificity in the dopamine D2-like receptors and related biogenic amine receptor, how agonist binding is transduced into G protein activation, and the structural basis for G protein-coupled receptor (GPCR) oligomerization and its role in signaling. In the pursuit of these objectives we are carrying out research on the dopamine D2 receptor as well as several other GPCRs. The D2 receptor is the principal target of antipsychotic drugs used in the treatment of schizophrenia.
Other research in his laboratory is focused on determining the structural bases of the transport of substrate by the dopamine transporter and its inhibition by drugs such as cocaine and amphetamine. The laboratory is also studying regulation of the trafficking and function of the dopamine transporter and its role in sensitization. Several lines of evidence support the relevance of sensitization to the pathophysiology of schizophrenia, including the ability of amphetamine and other psychostimulants to induce psychosis in normal subjects and the increased sensitivity of patients with schizophrenia to the psychotogenic effects of psychostimulants.
The laboratory also studies a number of bacterial homologs of the neurotransmitter transporters as model systems for direct structural studies, including X-ray crystallography, EPR spectroscopy, and single-molecule fluorescence spectroscopy, which they are pursuing in collaboration with colleagues. Their work focuses primarily on the molecular and cellular level, and they also are using mice and fruit flies as model systems to probe the relevance of these molecular details to psychostimulant-induced behaviors.