Faculty Appointments
Assistant Professor of Pharmacology
Education
Ph.D., Molecular Pharmacology, Columbia University, New York, New YorkB.A., Biology, Boston University, Boston, Massachusetts
Research Description
Dr. Donthamsetti develops cutting-edge molecular tools to uncover the complex interplay between neural signaling and behavior in health and disease. His laboratory employs a multidisciplinary approach that spans molecular biology, high-throughput screening, microscopy, electrophysiology, and rodent studies. His work focuses on uncovering the role of neuronal G protein-coupled receptors (GPCRs) using highly precise pharmacological techniques and optical biosensors that are developed in-house. In particular, his work has enabled us to target dopamine and glutamate receptors in the brain with unprecedented cellular and spatiotemporal precision, which could enhance our understanding of neurological disorders such as addiction, schizophrenia, and Parkinson's disease.
Research Keywords
Pharmacology, Molecular Pharmacology, Neuropharmacology, Neuroscience, Cellular and Molecular Neuroscience Chemical Biology, Drug Design, Molecular Biology,
Gene Therapy, Photopharmacology, Optogenetics, Molecular tools, G protein-coupled receptor, GPCR, Receptor, Behavior, Dopamine, Ion channels, Neurotransmission, Neuromodulation
Publications
Hetzler BE, Donthamsetti P, Peitsinis Z, Stanley C, Trauner D, Isacoff EY. Optical Control of Dopamine D2-like Receptors with Cell-Specific Fast-Relaxing Photoswitches. J Am Chem Soc [print-electronic]. 2023 Aug 8/16/2023; PMID: 37586061, DOI: 10.1021/jacs.3c02735, ISSN: 1520-5126.
Berry MH, Holt A, Broichhagen J, Donthamsetti P, Flannery JG, Isacoff EY. Photopharmacology for vision restoration. Curr Opin Pharmacol [print-electronic]. 2022 Aug; 65: 102259. PMID: 35749908, PII: S1471-4892(22)00086-8, DOI: 10.1016/j.coph.2022.102259, ISSN: 1471-4973.
Donthamsetti P, Winter N, Hoagland A, Stanley C, Visel M, Lammel S, Trauner D, Isacoff E. Cell specific photoswitchable agonist for reversible control of endogenous dopamine receptors. Nat Commun. 2021 Aug 8/6/2021; 12(1): 4775. PMID: 34362914, PMCID: PMC8346604, PII: 10.1038/s41467-021-25003-w, DOI: 10.1038/s41467-021-25003-w, ISSN: 2041-1723.
Donthamsetti P, Konrad DB, Hetzler B, Fu Z, Trauner D, Isacoff EY. Selective Photoswitchable Allosteric Agonist of a G Protein-Coupled Receptor. J Am Chem Soc [print-electronic]. 2021 Jun 6/23/2021; 143(24): 8951-6. PMID: 34115935, PMCID: PMC8227462, DOI: 10.1021/jacs.1c02586, ISSN: 1520-5126.
Farino ZJ, Morgenstern TJ, Maffei A, Quick M, De Solis AJ, Wiriyasermkul P, Freyberg RJ, Aslanoglou D, Sorisio D, Inbar BP, Free RB, Donthamsetti P, Mosharov EV, Kellendonk C, Schwartz GJ, Sibley DR, Schmauss C, Zeltser LM, Moore H, Harris PE, Javitch JA, Freyberg Z. New roles for dopamine D2 and D3 receptors in pancreatic beta cell insulin secretion. Mol Psychiatry [print-electronic]. 2020 Sep; 25(9): 2070-85. PMID: 30626912, PMCID: PMC6616020, PII: 10.1038/s41380-018-0344-6, DOI: 10.1038/s41380-018-0344-6, ISSN: 1476-5578.
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 [print-electronic]. 2020 Sep; 25(9): 2086-100. PMID: 30120413, PMCID: PMC6378141, PII: 10.1038/s41380-018-0212-4, DOI: 10.1038/s41380-018-0212-4, ISSN: 1476-5578.
Morstein J, Dacheux MA, Norman DD, Shemet A, Donthamsetti PC, Citir M, Frank JA, Schultz C, Isacoff EY, Parrill AL, Tigyi GJ, Trauner D. Optical Control of Lysophosphatidic Acid Signaling. J Am Chem Soc [print-electronic]. 2020 Jun 6/17/2020; 142(24): 10612-6. PMID: 32469525, PMCID: PMC7920854, DOI: 10.1021/jacs.0c02154, ISSN: 1520-5126.
Donthamsetti PC, Broichhagen J, Vyklicky V, Stanley C, Fu Z, Visel M, Levitz JL, Javitch JA, Trauner D, Isacoff EY. Genetically Targeted Optical Control of an Endogenous G Protein-Coupled Receptor. J Am Chem Soc [print-electronic]. 2019 Jul 7/24/2019; 141(29): 11522-30. PMID: 31291105, PMCID: PMC7271769, DOI: 10.1021/jacs.9b02895, ISSN: 1520-5126.
Morstein J, Hill RZ, Novak AJE, Feng S, Norman DD, Donthamsetti PC, Frank JA, Harayama T, Williams BM, Parrill AL, Tigyi GJ, Riezman H, Isacoff EY, Bautista DM, Trauner D. Optical control of sphingosine-1-phosphate formation and function. Nat Chem Biol [print-electronic]. 2019 Jun; 15(6): 623-31. PMID: 31036923, PMCID: PMC7428055, PII: 10.1038/s41589-019-0269-7, DOI: 10.1038/s41589-019-0269-7, ISSN: 1552-4469.
Marcott PF, Gong S, Donthamsetti P, Grinnell SG, Nelson MN, Newman AH, Birnbaumer L, Martemyanov KA, Javitch JA, Ford CP. Regional Heterogeneity of D2-Receptor Signaling in the Dorsal Striatum and Nucleus Accumbens. Neuron [print-electronic]. 2018 May 5/2/2018; 98(3): 575-587.e4-587.e4. PMID: 29656874, PMCID: PMC6048973, PII: S0896-6273(18)30244-7, DOI: 10.1016/j.neuron.2018.03.038, ISSN: 1097-4199.
Donthamsetti PC, Winter N, Schönberger M, Levitz J, Stanley C, Javitch JA, Isacoff EY, Trauner D. Optical Control of Dopamine Receptors Using a Photoswitchable Tethered Inverse Agonist. J Am Chem Soc [print-electronic]. 2017 Dec 12/27/2017; 139(51): 18522-35. PMID: 29166564, PMCID: PMC5942546, DOI: 10.1021/jacs.7b07659, ISSN: 1520-5126.
Michino M, Boateng CA, Donthamsetti P, Yano H, Bakare OM, Bonifazi A, Ellenberger MP, Keck TM, Kumar V, Zhu C, Verma R, Deschamps JR, Javitch JA, Newman AH, Shi L. Toward Understanding the Structural Basis of Partial Agonism at the Dopamine D3 Receptor. J Med Chem [print-electronic]. 2017 Jan 1/26/2017; 60(2): 580-93. PMID: 27983845, PMCID: PMC5563258, DOI: 10.1021/acs.jmedchem.6b01148, ISSN: 1520-4804.
Zou MF, Keck TM, Kumar V, Donthamsetti P, Michino M, Burzynski C, Schweppe C, Bonifazi A, Free RB, Sibley DR, Janowsky A, Shi L, Javitch JA, Newman AH. Novel Analogues of (R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (Sumanirole) Provide Clues to Dopamine D2/D3 Receptor Agonist Selectivity. J Med Chem [print-electronic]. 2016 Apr 4/14/2016; 59(7): 2973-88. PMID: 27035329, PMCID: PMC4915350, DOI: 10.1021/acs.jmedchem.5b01612, ISSN: 1520-4804.
Klein Herenbrink C, Sykes DA, Donthamsetti P, Canals M, Coudrat T, Shonberg J, Scammells PJ, Capuano B, Sexton PM, Charlton SJ, Javitch JA, Christopoulos A, Lane JR. The role of kinetic context in apparent biased agonism at GPCRs. Nat Commun. 2016 Feb 2/24/2016; 7: 10842. PMID: 26905976, PMCID: PMC4770093, PII: ncomms10842, DOI: 10.1038/ncomms10842, ISSN: 2041-1723.
Farino ZJ, Morgenstern TJ, Vallaghe J, Gregor N, Donthamsetti P, Harris PE, Pierre N, Freyberg R, Charrier-Savournin F, Javitch JA, Freyberg Z. Development of a Rapid Insulin Assay by Homogenous Time-Resolved Fluorescence. PLoS One. 2016; 11(2): e0148684. PMID: 26849707, PMCID: PMC4743966, PII: PONE-D-15-42142, DOI: 10.1371/journal.pone.0148684, ISSN: 1932-6203.
Donthamsetti P, Quejada JR, Javitch JA, Gurevich VV, Lambert NA. Using Bioluminescence Resonance Energy Transfer (BRET) to Characterize Agonist-Induced Arrestin Recruitment to Modified and Unmodified G Protein-Coupled Receptors. Curr Protoc Pharmacol. 2015 Sep 9/1/2015; 70: 2.14.1-2.14.14-2.14.14. PMID: 26331887, PMCID: PMC4583203, DOI: 10.1002/0471141755.ph0214s70, ISSN: 1934-8290.
Boateng CA, Bakare OM, Zhan J, Banala AK, Burzynski C, Pommier E, Keck TM, Donthamsetti P, Javitch JA, Rais R, Slusher BS, Xi ZX, Newman AH. High Affinity Dopamine D3 Receptor (D3R)-Selective Antagonists Attenuate Heroin Self-Administration in Wild-Type but not D3R Knockout Mice. J Med Chem [print-electronic]. 2015 Aug 8/13/2015; 58(15): 6195-213. PMID: 26203768, PMCID: PMC4937837, DOI: 10.1021/acs.jmedchem.5b00776, ISSN: 1520-4804.
Michino M, Beuming T, Donthamsetti P, Newman AH, Javitch JA, Shi L. What can crystal structures of aminergic receptors tell us about designing subtype-selective ligands?. Pharmacol Rev. 2015; 67(1): 198-213. PMID: 25527701, PMCID: PMC4279073, PII: 67/1/198, DOI: 10.1124/pr.114.009944, ISSN: 1521-0081.
Clayton CC, Donthamsetti P, Lambert NA, Javitch JA, Neve KA. Mutation of three residues in the third intracellular loop of the dopamine D2 receptor creates an internalization-defective receptor. J Biol Chem [print-electronic]. 2014 Nov 11/28/2014; 289(48): 33663-75. PMID: 25336643, PMCID: PMC4246117, PII: S0021-9258(20)47439-3, DOI: 10.1074/jbc.M114.605378, ISSN: 1083-351X.
Lane JR, Donthamsetti P, Shonberg J, Draper-Joyce CJ, Dentry S, Michino M, Shi L, López L, Scammells PJ, Capuano B, Sexton PM, Javitch JA, Christopoulos A. A new mechanism of allostery in a G protein-coupled receptor dimer. Nat Chem Biol [print-electronic]. 2014 Sep; 10(9): 745-52. PMID: 25108820, PMCID: PMC4138267, PII: nchembio.1593, DOI: 10.1038/nchembio.1593, ISSN: 1552-4469.
Michino M, Donthamsetti P, Beuming T, Banala A, Duan L, Roux T, Han Y, Trinquet E, Newman AH, Javitch JA, Shi L. A single glycine in extracellular loop 1 is the critical determinant for pharmacological specificity of dopamine D2 and D3 receptors. Mol Pharmacol [print-electronic]. 2013 Dec; 84(6): 854-64. PMID: 24061855, PMCID: PMC3834143, PII: mol.113.087833, DOI: 10.1124/mol.113.087833, ISSN: 1521-0111.
Newman AH, Beuming T, Banala AK, Donthamsetti P, Pongetti K, LaBounty A, Levy B, Cao J, Michino M, Luedtke RR, Javitch JA, Shi L. Molecular determinants of selectivity and efficacy at the dopamine D3 receptor. J Med Chem [print-electronic]. 2012 Aug 8/9/2012; 55(15): 6689-99. PMID: 22632094, PMCID: PMC3415572, DOI: 10.1021/jm300482h, ISSN: 1520-4804.
Seo KY, Yin J, Donthamsetti P, Chandani S, Lee CH, Loechler EL. Amino acid architecture that influences dNTP insertion efficiency in Y-family DNA polymerase V of E. coli. J Mol Biol [print-electronic]. 2009 Sep 9/18/2009; 392(2): 270-82. PMID: 19607844, PMCID: PMC2766551, PII: S0022-2836(09)00843-2, DOI: 10.1016/j.jmb.2009.07.016, ISSN: 1089-8638.
Berry MH, Holt A, Broichhagen J, Donthamsetti P, Flannery JG, Isacoff EY. Photopharmacology for vision restoration. Curr Opin Pharmacol [print-electronic]. 2022 Aug; 65: 102259. PMID: 35749908, PII: S1471-4892(22)00086-8, DOI: 10.1016/j.coph.2022.102259, ISSN: 1471-4973.
Donthamsetti P, Winter N, Hoagland A, Stanley C, Visel M, Lammel S, Trauner D, Isacoff E. Cell specific photoswitchable agonist for reversible control of endogenous dopamine receptors. Nat Commun. 2021 Aug 8/6/2021; 12(1): 4775. PMID: 34362914, PMCID: PMC8346604, PII: 10.1038/s41467-021-25003-w, DOI: 10.1038/s41467-021-25003-w, ISSN: 2041-1723.
Donthamsetti P, Konrad DB, Hetzler B, Fu Z, Trauner D, Isacoff EY. Selective Photoswitchable Allosteric Agonist of a G Protein-Coupled Receptor. J Am Chem Soc [print-electronic]. 2021 Jun 6/23/2021; 143(24): 8951-6. PMID: 34115935, PMCID: PMC8227462, DOI: 10.1021/jacs.1c02586, ISSN: 1520-5126.
Farino ZJ, Morgenstern TJ, Maffei A, Quick M, De Solis AJ, Wiriyasermkul P, Freyberg RJ, Aslanoglou D, Sorisio D, Inbar BP, Free RB, Donthamsetti P, Mosharov EV, Kellendonk C, Schwartz GJ, Sibley DR, Schmauss C, Zeltser LM, Moore H, Harris PE, Javitch JA, Freyberg Z. New roles for dopamine D2 and D3 receptors in pancreatic beta cell insulin secretion. Mol Psychiatry [print-electronic]. 2020 Sep; 25(9): 2070-85. PMID: 30626912, PMCID: PMC6616020, PII: 10.1038/s41380-018-0344-6, DOI: 10.1038/s41380-018-0344-6, ISSN: 1476-5578.
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 [print-electronic]. 2020 Sep; 25(9): 2086-100. PMID: 30120413, PMCID: PMC6378141, PII: 10.1038/s41380-018-0212-4, DOI: 10.1038/s41380-018-0212-4, ISSN: 1476-5578.
Morstein J, Dacheux MA, Norman DD, Shemet A, Donthamsetti PC, Citir M, Frank JA, Schultz C, Isacoff EY, Parrill AL, Tigyi GJ, Trauner D. Optical Control of Lysophosphatidic Acid Signaling. J Am Chem Soc [print-electronic]. 2020 Jun 6/17/2020; 142(24): 10612-6. PMID: 32469525, PMCID: PMC7920854, DOI: 10.1021/jacs.0c02154, ISSN: 1520-5126.
Donthamsetti PC, Broichhagen J, Vyklicky V, Stanley C, Fu Z, Visel M, Levitz JL, Javitch JA, Trauner D, Isacoff EY. Genetically Targeted Optical Control of an Endogenous G Protein-Coupled Receptor. J Am Chem Soc [print-electronic]. 2019 Jul 7/24/2019; 141(29): 11522-30. PMID: 31291105, PMCID: PMC7271769, DOI: 10.1021/jacs.9b02895, ISSN: 1520-5126.
Morstein J, Hill RZ, Novak AJE, Feng S, Norman DD, Donthamsetti PC, Frank JA, Harayama T, Williams BM, Parrill AL, Tigyi GJ, Riezman H, Isacoff EY, Bautista DM, Trauner D. Optical control of sphingosine-1-phosphate formation and function. Nat Chem Biol [print-electronic]. 2019 Jun; 15(6): 623-31. PMID: 31036923, PMCID: PMC7428055, PII: 10.1038/s41589-019-0269-7, DOI: 10.1038/s41589-019-0269-7, ISSN: 1552-4469.
Marcott PF, Gong S, Donthamsetti P, Grinnell SG, Nelson MN, Newman AH, Birnbaumer L, Martemyanov KA, Javitch JA, Ford CP. Regional Heterogeneity of D2-Receptor Signaling in the Dorsal Striatum and Nucleus Accumbens. Neuron [print-electronic]. 2018 May 5/2/2018; 98(3): 575-587.e4-587.e4. PMID: 29656874, PMCID: PMC6048973, PII: S0896-6273(18)30244-7, DOI: 10.1016/j.neuron.2018.03.038, ISSN: 1097-4199.
Donthamsetti PC, Winter N, Schönberger M, Levitz J, Stanley C, Javitch JA, Isacoff EY, Trauner D. Optical Control of Dopamine Receptors Using a Photoswitchable Tethered Inverse Agonist. J Am Chem Soc [print-electronic]. 2017 Dec 12/27/2017; 139(51): 18522-35. PMID: 29166564, PMCID: PMC5942546, DOI: 10.1021/jacs.7b07659, ISSN: 1520-5126.
Michino M, Boateng CA, Donthamsetti P, Yano H, Bakare OM, Bonifazi A, Ellenberger MP, Keck TM, Kumar V, Zhu C, Verma R, Deschamps JR, Javitch JA, Newman AH, Shi L. Toward Understanding the Structural Basis of Partial Agonism at the Dopamine D3 Receptor. J Med Chem [print-electronic]. 2017 Jan 1/26/2017; 60(2): 580-93. PMID: 27983845, PMCID: PMC5563258, DOI: 10.1021/acs.jmedchem.6b01148, ISSN: 1520-4804.
Zou MF, Keck TM, Kumar V, Donthamsetti P, Michino M, Burzynski C, Schweppe C, Bonifazi A, Free RB, Sibley DR, Janowsky A, Shi L, Javitch JA, Newman AH. Novel Analogues of (R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (Sumanirole) Provide Clues to Dopamine D2/D3 Receptor Agonist Selectivity. J Med Chem [print-electronic]. 2016 Apr 4/14/2016; 59(7): 2973-88. PMID: 27035329, PMCID: PMC4915350, DOI: 10.1021/acs.jmedchem.5b01612, ISSN: 1520-4804.
Klein Herenbrink C, Sykes DA, Donthamsetti P, Canals M, Coudrat T, Shonberg J, Scammells PJ, Capuano B, Sexton PM, Charlton SJ, Javitch JA, Christopoulos A, Lane JR. The role of kinetic context in apparent biased agonism at GPCRs. Nat Commun. 2016 Feb 2/24/2016; 7: 10842. PMID: 26905976, PMCID: PMC4770093, PII: ncomms10842, DOI: 10.1038/ncomms10842, ISSN: 2041-1723.
Farino ZJ, Morgenstern TJ, Vallaghe J, Gregor N, Donthamsetti P, Harris PE, Pierre N, Freyberg R, Charrier-Savournin F, Javitch JA, Freyberg Z. Development of a Rapid Insulin Assay by Homogenous Time-Resolved Fluorescence. PLoS One. 2016; 11(2): e0148684. PMID: 26849707, PMCID: PMC4743966, PII: PONE-D-15-42142, DOI: 10.1371/journal.pone.0148684, ISSN: 1932-6203.
Donthamsetti P, Quejada JR, Javitch JA, Gurevich VV, Lambert NA. Using Bioluminescence Resonance Energy Transfer (BRET) to Characterize Agonist-Induced Arrestin Recruitment to Modified and Unmodified G Protein-Coupled Receptors. Curr Protoc Pharmacol. 2015 Sep 9/1/2015; 70: 2.14.1-2.14.14-2.14.14. PMID: 26331887, PMCID: PMC4583203, DOI: 10.1002/0471141755.ph0214s70, ISSN: 1934-8290.
Boateng CA, Bakare OM, Zhan J, Banala AK, Burzynski C, Pommier E, Keck TM, Donthamsetti P, Javitch JA, Rais R, Slusher BS, Xi ZX, Newman AH. High Affinity Dopamine D3 Receptor (D3R)-Selective Antagonists Attenuate Heroin Self-Administration in Wild-Type but not D3R Knockout Mice. J Med Chem [print-electronic]. 2015 Aug 8/13/2015; 58(15): 6195-213. PMID: 26203768, PMCID: PMC4937837, DOI: 10.1021/acs.jmedchem.5b00776, ISSN: 1520-4804.
Michino M, Beuming T, Donthamsetti P, Newman AH, Javitch JA, Shi L. What can crystal structures of aminergic receptors tell us about designing subtype-selective ligands?. Pharmacol Rev. 2015; 67(1): 198-213. PMID: 25527701, PMCID: PMC4279073, PII: 67/1/198, DOI: 10.1124/pr.114.009944, ISSN: 1521-0081.
Clayton CC, Donthamsetti P, Lambert NA, Javitch JA, Neve KA. Mutation of three residues in the third intracellular loop of the dopamine D2 receptor creates an internalization-defective receptor. J Biol Chem [print-electronic]. 2014 Nov 11/28/2014; 289(48): 33663-75. PMID: 25336643, PMCID: PMC4246117, PII: S0021-9258(20)47439-3, DOI: 10.1074/jbc.M114.605378, ISSN: 1083-351X.
Lane JR, Donthamsetti P, Shonberg J, Draper-Joyce CJ, Dentry S, Michino M, Shi L, López L, Scammells PJ, Capuano B, Sexton PM, Javitch JA, Christopoulos A. A new mechanism of allostery in a G protein-coupled receptor dimer. Nat Chem Biol [print-electronic]. 2014 Sep; 10(9): 745-52. PMID: 25108820, PMCID: PMC4138267, PII: nchembio.1593, DOI: 10.1038/nchembio.1593, ISSN: 1552-4469.
Michino M, Donthamsetti P, Beuming T, Banala A, Duan L, Roux T, Han Y, Trinquet E, Newman AH, Javitch JA, Shi L. A single glycine in extracellular loop 1 is the critical determinant for pharmacological specificity of dopamine D2 and D3 receptors. Mol Pharmacol [print-electronic]. 2013 Dec; 84(6): 854-64. PMID: 24061855, PMCID: PMC3834143, PII: mol.113.087833, DOI: 10.1124/mol.113.087833, ISSN: 1521-0111.
Newman AH, Beuming T, Banala AK, Donthamsetti P, Pongetti K, LaBounty A, Levy B, Cao J, Michino M, Luedtke RR, Javitch JA, Shi L. Molecular determinants of selectivity and efficacy at the dopamine D3 receptor. J Med Chem [print-electronic]. 2012 Aug 8/9/2012; 55(15): 6689-99. PMID: 22632094, PMCID: PMC3415572, DOI: 10.1021/jm300482h, ISSN: 1520-4804.
Seo KY, Yin J, Donthamsetti P, Chandani S, Lee CH, Loechler EL. Amino acid architecture that influences dNTP insertion efficiency in Y-family DNA polymerase V of E. coli. J Mol Biol [print-electronic]. 2009 Sep 9/18/2009; 392(2): 270-82. PMID: 19607844, PMCID: PMC2766551, PII: S0022-2836(09)00843-2, DOI: 10.1016/j.jmb.2009.07.016, ISSN: 1089-8638.