Jonathan Javitch, M.D., Ph.D.
Professor of Physiology & Cellular Biophysics, and Psychiatry and Pharmacology
Structure, function and regulation of G-Protein-Coupled receptors and neurotransmitter transporters.
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.
His research focuses on the structure, function and regulation of G protein-coupled receptors and neurotransmitter transporters, with an emphasis on dopamine D2 receptor and dopamine transporter, the targets, respectively, for antipsychotic drugs and psychostimulants, using biochemical and biophysical approaches to elucidate molecular mechanisms of drug action, receptor signaling and sodium-coupled transport. His studies of GPCRs are uncovering unappreciated regulation of signaling by heteromeric complexes of receptors, raising the possibility of a novel approach to drug design and screening. In collaboration with leading experts in the field, his laboratory is also pursuing single molecule fluorescence spectroscopy, electron paramagnetic resonance spectroscopy, and crystallographic studies of bacterial homologs of neurotransmitter transporters to explicate the mechanisms of sodium-coupled transport and the actions of antidepressant drugs that inhibit transport. He is also studying the function and regulation of dopamine transporter and dopamine receptors in the fruit fly Drosophila melanogaster, in which his laboratory has developed approaches to translate between molecular mechanisms and whole organism behavior using the power of fly genetics.
Asher WB, Geggier P, Holsey MD, Gilmore GT, Pati AK, Meszaros J, Terry DS,
Mathiasen S, Kaliszewski MJ, McCauley MD, Govindaraju A, Zhou Z, Harikumar KG,
Jaqaman K, Miller LJ, Smith AW, Blanchard SC, Javitch JA. Single-molecule FRET
imaging of GPCR dimers in living cells. Nat Methods. 2021 Apr;18(4):397-405.
doi: 10.1038/s41592-021-01081-y. Epub 2021 Mar 8. PMID: 33686301; PMCID:
Donthamsetti P, Gallo EF, Buck DC, Stahl EL, Zhu Y, Lane JR, Bohn LM, Neve
KA, Kellendonk C, Javitch JA. Arrestin recruitment to dopamine D2 receptor
mediates locomotion but not incentive motivation. Mol Psychiatry. 2020
Sep;25(9):2086-2100. doi: 10.1038/s41380-018-0212-4. Epub 2018 Aug 17. PMID:
30120413; PMCID: PMC6378141.
Mathiasen S, Palmisano T, Perry NA, Stoveken HM, Vizurraga A, McEwen DP,
Okashah N, Langenhan T, Inoue A, Lambert NA, Tall GG, Javitch JA. G12/13 is
activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3. Nat
Chem Biol. 2020 Dec;16(12):1343-1350. doi: 10.1038/s41589-020-0617-7. Epub 2020
Aug 10. Erratum in: Nat Chem Biol. 2020 Aug 17;: PMID: 32778842; PMCID:
Fitzgerald GA, Terry DS, Warren AL, Quick M, Javitch JA, Blanchard SC.
Quantifying secondary transport at single-molecule resolution. Nature. 2019
Nov;575(7783):528-534. doi: 10.1038/s41586-019-1747-5. Epub 2019 Nov 13.
Freyberg Z, Sonders MS, Aguilar JI, Hiranita T, Karam CS, Flores J, Pizzo AB,
Zhang Y, Farino ZJ, Chen A, Martin CA, Kopajtic TA, Fei H, Hu G, Lin YY,
Mosharov EV, McCabe BD, Freyberg R, Wimalasena K, Hsin LW, Sames D, Krantz DE,
Katz JL, Sulzer D, Javitch JA. Mechanisms of amphetamine action illuminated
through optical monitoring of dopamine synaptic vesicles in Drosophila brain.
Nat Commun. 2016 Feb 16;7:10652. doi: 10.1038/ncomms10652. PMID: 26879809;