Gabriela K. Popescu PhD
Gabriela K. Popescu
PhD
Professor
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Ion channel kinetics and structure; Molecular Basis of Disease; Neurobiology; Neurodegenerative disorders; Neuropharmacology; Protein Function and Structure; Signal Transduction
Professional Summary:
We investigate the activation mechanisms of fast neurotransmitter receptors. We seek to define the activation pathway, modulatory mechanisms and structure-function relationships of the N-methyl-D-aspartate (NMDA) receptor to better understand the roles played by this protein in the brain.
NMDA receptors are the most abundant glutamate-stimulated, Ca2+-conducting ion channels in brain and spinal cord. They are the predominant molecular devices for controlling synaptic development and plasticity and govern memory and learning processes. Understanding the mechanisms that control their activity may lead to more effective strategies to treat neuropathies including stroke, neurodegenerative conditions, chronic pain and addiction as well as mental disorders such as schizophrenia and epilepsy.
Education and Training:
- Fellowship, Biophysics, University at Buffalo, SUNY (2005)
- PhD, Biochemistry, University at Buffalo, SUNY (1999)
- MS, Biochemistry, University of Bucharest (1985)
Employment:
- Professor, Biochemistry, University at Buffalo, SUNY Jacobs School of Medicine & Biomedical Sciences (2014-present)
- Adjunct Faculty, Anesthesiology, University at Buffalo, SUNY Jacobs School of Medicine & Biomedical Sciences (2005-present)
- Adjunct Faculty, Physiology and Biophysics, University at Buffalo, SUNY Jacobs School of Medicine & Biomedical Sciences (2005-present)
- Associate Professor, Biochemistry, University at Buffalo, SUNY Jacobs School of Medicine & Biomedical Sciences (2011–2013)
- Assistant Professor, Biochemistry, University at Buffalo, SUNY Jacobs School of Medicine & Biomedical Sciences (2006–2010)
Awards and Honors:
- Chair, AAMC Council of Faculty (2019)
- Member, AAMC Board of Directors (2017)
- AHA, Established Investigator Award (2012)
- Public Lecture - Glutamate Receptors: the workhorses of your memory (2011)
- UB Exceptional Scholars, Young Investigator Award (2010)
- NIH/NINDS Principal Investigator (2006)
- NIH/NIDA NRSA (2001)
Research Expertise:
- Electrophysiology
- Excitotoxicity
- Ligand gated ion-channels
- Molecular neurophysiology
- Molecular neuroscience
- Molecular pharmacology
- Neurodegeneration
- Neurophysiology
- NMDA RECEPTORS
- Single-molecule techniques
- Synaptic plasticity
- Synaptic transmission
UB 2020 Strategic Strengths:
- Molecular Recognition in Biological Systems and Bioinformatics
Grants and Sponsored Research:
- April 2019–April 2024
Gating Mechanism of NMDA receptors
NIH/NINDS
Role: Principal Investigator - March 2016–February 2022
Permeation Mechanisms in NMDA receptors
NIH/NINDS
Role: Principal Investigator
$1,373,000 - January 2016–January 2018
MECHANICAL ACTIVATION OF NMDA RECEPTORS
NINDS
Role: Principal Investigator
$275,000 - January 2012–December 2016
Selective modulation of native NMDA receptors
AHA Established Investigator Award
Role: Principal Investigator
$400,000 - July 2006–April 2016
Allosteric Modulation of NMDA receptors
NINDS/R01
Role: Principal Investigator
$3,900,000 - September 2010–May 2012
Calcium modulation of synaptic receptors
SUNY/REACH
Role: Co-Investigator
$30,000 - June 2008–May 2010
NMDA receptors with restricted mobility of ligand-binding domains
NIDA/R03
Role: Principal Investigator
$144,000 - July 2005–June 2009
Modulation of NMDA receptor by neurosteroids
AHA Scientist Development Grant
Role: Principal Investigator
$160,000 - August 2001–August 2004
NMDA Receptor: kinetic modeling and mapping of the glutamate-binding domain
NIH/NRSA F32
Role: Principal Investigator
$120,000
Journal Articles:
- Iacobucci GJ, Popescu GK. (2017) NMDA receptors: linking physiological output to biophysical operation. Nat Rev Neurosci (Jan), 18(4): 236-249.
- Maneshi MM, Maki B, Gnanasambandam R, Belin S, Popescu GK, Sachs F, Hua SZ. (2017) Mechanical stress activates NMDA receptors in the absence of agonists. Sci Rep (Jan), 7: 39610-39610.
- Chai X, Zhai Y, Popescu G, Napoli JL. (1995) Cloning of a cDNA for a second retinol dehydrogenase type II. Expression of its mRNA relative to type I. J Biol Chem (Nov), 270(47): 28408-28412.
- Iacobucci GJ, Wen H, Helou M, Liu B, Zheng W, Popescu GK. (2021) Cross-subunit interactions that stabilize open states mediate gating in NMDA receptors. Proceedings of the National Academy of Sciences of the United States of America (Jan), 118(2). doi:10.1073/pnas.2007511118
- Popescu GK. (2020) FRET-ting over Inactivation. Biophysical journal (Dec), 119(11): 2139-2140. doi:10.1016/j.bpj.2020.10.015
- Abbott JA, Popescu GK. (2020) Hydroxynorketamine Blocks N-Methyl-d-Aspartate Receptor Currents by Binding to Closed Receptors. Molecular pharmacology (Sep), 98(3): 203-210. doi:10.1124/mol.120.119784
- Iacobucci GJ, Popescu GK. (2020) Ca2+-Dependent Inactivation of GluN2A and GluN2B NMDA Receptors Occurs by a Common Kinetic Mechanism. Biophysical journal (Feb), 118(4): 798-812. doi:10.1016/j.bpj.2019.07.057
- Iacobucci GJ, Popescu GK. (2019) Spatial Coupling Tunes NMDA Receptor Responses via Ca2+ Diffusion. The Journal of neuroscience : the official journal of the Society for Neuroscience (Nov), 39(45): 8831-8844. doi:10.1523/JNEUROSCI.0901-19.2019
- Iacobucci GJ, Popescu GK. (2018) Kinetic models for activation and modulation of NMDA receptor subtypes. Curr Opin Physiol (Apr), 2: 114-122.
- Iacobucci GJ, Popescu GK. (2017) Resident Calmodulin Primes NMDA Receptors for Ca2+-Dependent Inactivation. Biophys J (Nov), 113(10): 2236-2248.
- Zheng W, Wen H, Iacobucci GJ, Popescu GK. (2017) Probing the Structural Dynamics of the NMDA Receptor Activation by Coarse-Grained Modeling. Biophys J (Jun), 112(12): 2589-2601.
- Cummings KA, Belin S, Popescu GK. (2017) Residues in the GluN1 C-terminal domain control kinetics and pharmacology of GluN1/GluN3A N-methyl-d-aspartate receptors. Neuropharmacology (Jun), 119: 40-47.
- Bajpai VK, Kerosuo L, Tseropoulos G, Cummings KA, Wang X, Lei P, Liu B, Liu S, Popescu GK, Bronner ME, Andreadis ST. (2017) Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates. Stem Cells (Jan).
- Cummings KA, Popescu GK. (2016) Protons Potentiate GluN1/GluN3A Currents by Attenuating Their Desensitisation. Sci Rep (Mar), 6: 23344-23344.
- Borschel WF, Cummings KA, Tindell LK, Popescu GK. (2015) Kinetic Contributions to Gating by Interactions Unique to N-methyl-d-aspartate (NMDA) Receptors. J Biol Chem (Oct), 290(44): 26846-26855.
- Cummings KA, Popescu GK. (2015) Glycine-dependent activation of NMDA receptors. J Gen Physiol (May).
- Paganelli MA, Popescu GK. (2015) Actions of bupivacaine, a widely used local anesthetic, on NMDA receptor responses. J Neurosci (Jan), 35(2): 831-842.
- Popescu GK. (2015) Accessories assist AMPA receptors to close pockets. J Gen Physiol (Jan), 145(1): 17-21.
- Maki BA, Popescu GK. (2014) Extracellular Ca(2+) ions reduce NMDA receptor conductance and gating. J Gen Physiol (Nov), 144(5): 379-392.
- Maki BA, Popescu GK. (2014) Extracellular Ca2+ ions reduce NMDA receptor conductance and gating. J Gen Physiol (Nov), 144(5): 379-392.
- Maki BA, Cummings KA, Paganelli MA, Murthy SE, Popescu GK. (2014) One-channel cell-attached patch-clamp recording. J Vis Exp (Jun)(88).
- Aman TK, Maki BA, Ruffino TJ, Kasperek EM, Popescu GK. (2014) Separate Intramolecular Targets for Protein Kinase A Control N-Methyl-d-aspartate Receptor Gating and Ca2+ Permeability. J Biol Chem (Jul), 289(27): 18805-18817.
- Murphy JA, Stein IS, Lau CG, Peixoto RT, Aman TK, Kaneko N, Aromolaran K, Saulnier JL, Popescu GK, Sabatini BL, Hell JW, Zukin RS. (2014) Phosphorylation of Ser1166 on GluN2B by PKA is critical to synaptic NMDA receptor function and Ca2+ signaling in spines. J Neurosci (Jan), 34(3): 869-879.
- Paganelli MA, Kussius CL, Popescu GK. (2013) Role of cross-cleft contacts in NMDA receptor gating. PLoS One (Nov), 8(11): 80953-80953.
- Yu H, Popescu GK. (2013) Inhibition of GluN2A-containing N-methyl-D-aspartate receptors by 2-naphthoic acid. Mol Pharmacol (Oct), 84(4): 541-550.
- Yu H, Popescu GK. (2013) Inhibition of GluN2A-containing NMDA Receptors by 2-Naphthoic Acid. Mol Pharmacol (Jul).
- Maki BA, Cole R, Popescu GK. (2013) Two serine residues on GluN2A C-terminal tails control NMDA receptor current decay times. Channels (Austin) (Mar), 7(2): 126-132.
- Borschel WF, Myers JM, Kasperek EM, Smith TP, Graziane NM, Nowak LM, Popescu GK. (2012) Gating reaction mechanism of neuronal NMDA receptors. J Neurophysiol (Dec), 108(11): 3105-3115.
- Maki BA, Aman TK, Amico-Ruvio SA, Kussius CL, Popescu GK. (2012) C-terminal Domains of N-Methyl-D-aspartic Acid Receptor Modulate Unitary Channel Conductance and Gating. J Biol Chem (Oct), 287(43): 36071-36080.
- Amico-Ruvio SA, Paganelli MA, Myers JM, Popescu GK. (2012) Ifenprodil Effects on GluN2B-Containing Glutamate Receptors. Mol Pharmacol (Dec), 82(6): 1074-1081.
- Murthy SE, Shogan T, Page JC, Kasperek EM, Popescu GK. (2012) Probing the activation sequence of NMDA receptors with lurcher mutations. J Gen Physiol (Sep), 140(3): 267-277.
- Popescu GK. (2012) Modes of glutamate receptor gating. J Physiol (Jan), 590(Pt 1): 73-91.
- Borschel WF, Murthy SE, Kasperek EM, Popescu GK. (2011) NMDA receptor activation requires remodelling of intersubunit contacts within ligand-binding heterodimers. Nat Commun (Oct), 2: 498-498.
- Amico-Ruvio SA, Murthy SE, Smith TP, Popescu GK. (2011) Zinc effects on NMDA receptor gating kinetics. Biophys J (Apr), 100(8): 1910-1918.
- Kussius CL, Popescu GK. (2010) NMDA receptors with locked glutamate-binding clefts open with high efficacy. J Neurosci (Sep), 30(37): 12474-12479.
- Amico-Ruvio SA, Popescu GK. (2010) Stationary gating of GluN1/GluN2B receptors in intact membrane patches. Biophys J (Apr), 98(7): 1160-1169.
- Kussius CL, Popescu AM, Popescu GK. (2010) Agonist-specific gating of NMDA receptors. Channels (Austin) (Mar), 4(2): 78-82.
- Kussius CL, Popescu GK. (2009) Kinetic basis of partial agonism at NMDA receptors. Nat Neurosci (Sep), 12(9): 1114-1120.
- Kussius CL, Kaur N, Popescu GK. (2009) Pregnanolone sulfate promotes desensitization of activated NMDA receptors. J Neurosci (May), 29(21): 6819-6827.
- Zhang W, Howe JR, Popescu GK. (2008) Distinct gating modes determine the biphasic relaxation of NMDA receptor currents. Nat Neurosci (Dec), 11(12): 1373-1375.
- Popescu G, Robert A, Howe JR, Auerbach A. (2004) Reaction mechanism determines NMDA receptor response to repetitive stimulation. Nature (Aug), 430(7001): 790-793.
- Popescu G, Auerbach A. (2004) The NMDA receptor gating machine: lessons from single channels. Neuroscientist (Jun), 10(3): 192-198.
- Peng H, Myers J, Fang X, Stachowiak EK, Maher PA, Martins GG, Popescu G, Berezney R, Stachowiak MK. (2002) Integrative nuclear FGFR1 signaling (INFS) pathway mediates activation of the tyrosine hydroxylase gene by angiotensin II, depolarization and protein kinase C. J Neurochem (May), 81(3): 506-524.
- Popescu G, Napoli JL. (2000) Analysis of rat cytosolic 9-cis-retinol dehydrogenase activity and enzymatic characterization of rat ADHII. Biochim Biophys Acta (Jan), 1476(1): 43-52.
- Popescu GK Murthy, SE Borschel, WF. (2010) Allosteric inhibitors of NMDA receptor functions. Pharmaceuticals (Dec)1910-1918.
- Popescu GK, Popescu AM, Kussius CL. (2010) Agonist-specific Action at NMDA Receptors. Channels (Austin) (Mar), 4(2).
- Wei Zhang, James. R. Howe, Gabriela K. Popescu. (2008) Distinct gating modes determine the biphasic relaxation of NMDA receptor currents. Nature Neuroscience (Oct).
- Popescu G. (2005) Mechanism-based targeting of NMDA receptor functions. Cellular and Molecular Life Sciences (Oct), 62(18).
- Popescu G, Auerbach A. (2003) Modal gating of NMDA receptors and the shape of their synaptic response. Nature Neuroscience (Apr).
- Popescu G. (2005) Principles of NMDA receptor allosteric modulation. Molecular Pharmacology (Oct), 68(4).
- Iacobucci GJ and Popescu GK. (2018) Kinetic Models for Activation and Modulation of NMDA Receptor Subtypes. Current Opinion in Physiology (Feb), 2: 114-122.
- Kussius CK Popescu GK. (2010) NMDA receptors with locked ligand-binding clefts open with high efficacy. J Neuroscience (Sep).
- Popescu GK, Amico-Ruvio SA. (2010) Stationary gating patterns of GluN1/GluN2B NMDA receptors in intact membrane patches. Biophysical Journal (Apr), 98(7).
Professional Memberships:
- ASBMB, American Society for Biochemistry and Molecular Biology (2014–present)
- ASPET, America Society for Pharmacology and Experimental Therapeutics (2012–present)
- AAMC, American Association of Medical Colleges (2012–present)
- IBRO, International Brain Research Organization (2000–present)
- SfN, Society for Neuroscience (1999–present)
- AAAS, American Association for the Advancement of Science (1999–present)
- BPS, Biophysical Society (1999–present)
- UBAA, UB Alumni Association
Presentations:
- "NMDA Receptors: Learning from Singles" University of Michigan, Pharmacology Seminar Series (2021)
- "Implementing Team Science" Buffalo CTSI Professional Development Series (2021)
- "The place of PhDs in the medical centers of tommorrow" AAMC CFAS Spring Conference; AAMC; CFAS (2017)
- "Glycinergic Excitatory Receptors" University of Washington, Physiology Seminar Series (2016)
- "Glycinergic excitatory receptors: NMDA receptors in name only" Gordon Research Conferences/Excitatory Transmission in Brain Function (2016)
- "Mechanisms in NMDA receptor signaling" Johns Hopkins University, Physiology Seminar Series (2015)
- "Why Support Basic Research" AAMC Annual Meeting; AAMC (2015)
- "NMDA Receptors: learning from singles" Harvard University, Molecular and Cell Biology Seminar Series (2015)
- "Participation in Faculty Governance" AAMC/Spring CFAS Meeting; AAMC (2015)
- "Glycinergic NMDA receptors" Biophysical Society Annual Meeting; Symposium on Molecules of Memory (2015)
- "Preserving Science" AAMC Annual Meeting; AAMC (2014)
- "NMDA receptors: Learning from Singles" RIT Student Research Seminar; Rochester Institute of Technology (2014)
- "New inhibitory interface in NMDA receptors" Gordon Research Conferences/Ion Channels (2012)
- "Glutamate Receptors: The workhorses of your memory" UB Summer Public Lecture Series (2011)
- "Modes of NMDA receptor gating" GEPROM Symposium on Membrane Proteins, Montreal (2011)
Service Activities:
- AAAS Steering Committee Section N (Medical Sciences), Member at Large; Member at large (2020–2024)
- Biophysical Journal; Associate Editor (2020–2022)
- Chair - AAMC, Council of Faculty and Academic Societies; Chair (2019–2021)
- AAMC, Council of Faculty and Academic Societies; Chair (2017–2023)
- AAMC, Board of Directors, Member; Board Member (2017–2021)
- Admissions Committee; Member (2017–2020)
- Decanal Review Committee; Member (2016–2017)
- JSMBS Faculty Council, Basic Science Representative; Member (2016–2018)
- Search Committee for Dean of Dental Medicine; Member (2015–2016)
- Search Committee for Junior Faculty in Biochemistry; Member (2015–2016)
- Biophysical Society, Committee on Professional Opportunities for Women (CPOW); Chair (2015–2021)
- Biophysical Society, Council; Councilor (2015–2018)
- Faculty Senate; Committee on Tenure, Promotion, and Priviledges; Chair (2014–2015)
- Faculty Council, Steering Committee on Tenure and Promotions; Member (2014–2017)
- NIH; NTRC;; Panel Member (2014–2020)
- UB Neuroscience Program Steering Committee; Member (2014–2016)
- Search Committee for Vice President of Faculty Affairs; Member (2014)
- Journal of Neurochemistry; Editorial Board Member (2013–2016)
- AAMC, CFAS Administrative Board; Member (2013–2016)
- NIH; NTRC;; Ad Hoc Reviewer (2013)
- Faculty Senate Executive Committee; Member (2013–2017)
- Faculty Senate; School Representative (2013–2017)
- BCH Graduate Affairs Committee; Director (2013–2014)
- Biochemistry, Graduate Affairs Committee; Director (2013–2014)
- Search Committee for Vice President of Communications; School Representative (2013)
- UB2020 Faculty Liaison Committee; School Representative (2013)
- Search Committee for Chairperson in Biochemistry; Member (2013)
- NIH; BPNS;; Ad Hoc Reviewer (2012–2014)
- MSTP, Admissions Committee; Member (2012–2018)
- Biophysical Society, Career Conversations; Panel Member (2012)
- British Research Council;; Grant Reviewer (2012–present)
- Biophysical Society, Committee on Professional Opportunities for Women (CPOW); Member (2011–2015)
- PPBS, Steering Committee; Member (2010–2012)
- Search Commitee for Chairperson in Microbiology and Immunology; Member (2010–2011)
- BCH Graduate Affairs Committee; Member (2010–2013)
- SUNY REACH, Neuroscience Consortium, Focus Group on Receptors and Brain Development; University Representative (2010–2016)
- Society for Neuroscience, Buffalo Chapter; President (2009–2010)
- Search Committee for HJKRI Director; Member (2009–2010)
- ZRG1-MDCN;; Ad Hoc Reviewer (2009–present)
- Search Committee for Junior Faculty in Pharmacology; Member (2008–2009)
- AHA/R1 Electrophysiology;; Panel Member (2008–present)
- Biochemistry, Seminar Program; Coordinator (2007–2008)
- Advisory Committee on Postdoctoral Education; Member (2006–2009)
- SfN Buffalo Chapter Steering Committee; Member (2006–2011)
- CHE;; Ad Hoc Reviewer (2006–present)
- NEA4;; Panel Member (2006–2007)
- UB Postdoctoral Education, Steering Committee; Member (2005–2008)