Gabriela K. Popescu PhD
Gabriela K. Popescu
PhD
Professor
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Ion channel kinetics and structure; Membrane Transport (Ion Transport); 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:
- Postdoctoral NRSA 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 (2014-present)
- Adjunct Faculty, Physiology and Biophysics, University at Buffalo, SUNY (2005-present)
- Adjunct Faculty, Anesthesiology, University at Buffalo, SUNY (2005-present)
- Associate Professor, Biochemistry, University at Buffalo, SUNY (2011–2013)
- Assistant Professor, Biochemistry, University at Buffalo, SUNY (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:
- March 2016–February 2020
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:
- Maneshi MM, Maki B, Gnanasambandam R, Belin S, Popescu GK, Sachs F, Hua SZ. Mechanical stress activates NMDA receptors in the absence of agonists. Sci Rep. 2017; 7.
- Iacobucci GJ and Popescu GK. Kinetic Models for Activation and Modulation of NMDA Receptor Subtypes. Current Opinion in Physiology. 2018; 2.
- Iacobucci GJ, Popescu GK. Resident Calmodulin Primes NMDA Receptors for Ca2+-Dependent Inactivation. Biophys J. 2017; 113(10).
- Zheng W, Wen H, Iacobucci GJ, Popescu GK. Probing the Structural Dynamics of the NMDA Receptor Activation by Coarse-Grained Modeling. Biophys J. 2017; 112(12).
- Cummings KA, Belin S, Popescu GK. Residues in the GluN1 C-terminal domain control kinetics and pharmacology of GluN1/GluN3A N-methyl-d-aspartate receptors. Neuropharmacology. 2017; 119.
- Bajpai VK, Kerosuo L, Tseropoulos G, Cummings KA, Wang X, Lei P, Liu B, Liu S, Popescu GK, Bronner ME, Andreadis ST. Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates. Stem Cells. 2017.
- Cummings KA, Popescu GK. Protons Potentiate GluN1/GluN3A Currents by Attenuating Their Desensitisation. Sci Rep. 2016; 6.
- Borschel WF, Cummings KA, Tindell LK, Popescu GK. Kinetic Contributions to Gating by Interactions Unique to N-methyl-d-aspartate (NMDA) Receptors. J Biol Chem. 2015; 290(44).
- Cummings KA, Popescu GK. Glycine-dependent activation of NMDA receptors. J Gen Physiol. 2015.
- Paganelli MA, Popescu GK. Actions of bupivacaine, a widely used local anesthetic, on NMDA receptor responses. J Neurosci. 2015; 35(2).
- Popescu GK. Accessories assist AMPA receptors to close pockets. J Gen Physiol. 2015; 145(1).
- Maki BA, Popescu GK. Extracellular Ca2+ ions reduce NMDA receptor conductance and gating. J Gen Physiol. 2014; 144(5).
- Maki BA, Popescu GK. Extracellular Ca(2+) ions reduce NMDA receptor conductance and gating. J Gen Physiol. 2014; 144(5).
- Aman TK, Maki BA, Ruffino TJ, Kasperek EM, Popescu GK. Separate Intramolecular Targets for Protein Kinase A Control N-Methyl-d-aspartate Receptor Gating and Ca2+ Permeability. J Biol Chem. 2014; 289(27).
- Maki BA, Cummings KA, Paganelli MA, Murthy SE, Popescu GK. One-channel cell-attached patch-clamp recording. J Vis Exp. 2014; (88).
- Murphy JA, Stein IS, Lau CG, Peixoto RT, Aman TK, Kaneko N, Aromolaran K, Saulnier JL, Popescu GK, Sabatini BL, Hell JW, Zukin RS. Phosphorylation of Ser1166 on GluN2B by PKA is critical to synaptic NMDA receptor function and Ca2+ signaling in spines. J Neurosci. 2014; 34(3).
- Paganelli MA, Kussius CL, Popescu GK. Role of cross-cleft contacts in NMDA receptor gating. PLoS One. 2013; 8(11).
- Yu H, Popescu GK. Inhibition of GluN2A-containing N-methyl-D-aspartate receptors by 2-naphthoic acid. Mol Pharmacol. 2013; 84(4).
- Yu H, Popescu GK. Inhibition of GluN2A-containing NMDA Receptors by 2-Naphthoic Acid. Mol Pharmacol. 2013.
- Maki BA, Cole R, Popescu GK. Two serine residues on GluN2A C-terminal tails control NMDA receptor current decay times. Channels (Austin). 2013; 7(2).
- Borschel WF, Myers JM, Kasperek EM, Smith TP, Graziane NM, Nowak LM, Popescu GK. Gating reaction mechanism of neuronal NMDA receptors. J Neurophysiol. 2012; 108(11).
- Amico-Ruvio SA, Paganelli MA, Myers JM, Popescu GK. Ifenprodil Effects on GluN2B-Containing Glutamate Receptors. Mol Pharmacol. 2012; 82(6).
- Maki BA, Aman TK, Amico-Ruvio SA, Kussius CL, Popescu GK. C-terminal Domains of N-Methyl-D-aspartic Acid Receptor Modulate Unitary Channel Conductance and Gating. J Biol Chem. 2012; 287(43).
- Murthy SE, Shogan T, Page JC, Kasperek EM, Popescu GK. Probing the activation sequence of NMDA receptors with lurcher mutations. J Gen Physiol. 2012; 140(3).
- Popescu GK. Modes of glutamate receptor gating. J Physiol. 2012; 590(Pt 1).
- Borschel WF, Murthy SE, Kasperek EM, Popescu GK. NMDA receptor activation requires remodelling of intersubunit contacts within ligand-binding heterodimers. Nat Commun. 2011; 2.
- Amico-Ruvio SA, Murthy SE, Smith TP, Popescu GK. Zinc effects on NMDA receptor gating kinetics. Biophys J. 2011; 100(8).
- Popescu GK Murthy, SE Borschel, WF. Allosteric inhibitors of NMDA receptor functions. Pharmaceuticals. 2010.
- Kussius CK Popescu GK. NMDA receptors with locked ligand-binding clefts open with high efficacy. J Neuroscience. 2010.
- Kussius CL, Popescu GK. NMDA receptors with locked glutamate-binding clefts open with high efficacy. J Neurosci. 2010; 30(37).
- Amico-Ruvio SA, Popescu GK. Stationary gating of GluN1/GluN2B receptors in intact membrane patches. Biophys J. 2010; 98(7).
- Popescu GK, Amico-Ruvio SA. Stationary gating patterns of GluN1/GluN2B NMDA receptors in intact membrane patches. Biophysical Journal. 2010; 98(7).
- Kussius CL, Popescu AM, Popescu GK. Agonist-specific gating of NMDA receptors. Channels (Austin). 2010; 4(2).
- Popescu GK, Popescu AM, Kussius CL. Agonist-specific Action at NMDA Receptors. Channels (Austin). 2010; 4(2).
- Kussius CL, Popescu GK. Kinetic basis of partial agonism at NMDA receptors. Nat Neurosci. 2009; 12(9).
- Kussius CL, Kaur N, Popescu GK. Pregnanolone sulfate promotes desensitization of activated NMDA receptors. J Neurosci. 2009; 29(21).
- Zhang W, Howe JR, Popescu GK. Distinct gating modes determine the biphasic relaxation of NMDA receptor currents. Nat Neurosci. 2008; 11(12).
- Wei Zhang, James. R. Howe, Gabriela K. Popescu. Distinct gating modes determine the biphasic relaxation of NMDA receptor currents. Nature Neuroscience. 2008.
- Popescu G. Mechanism-based targeting of NMDA receptor functions. Cellular and Molecular Life Sciences. 2005; 62(18).
- Popescu G. Principles of NMDA receptor allosteric modulation. Molecular Pharmacology. 2005; 68(4).
- Popescu G, Robert A, Howe JR, Auerbach A. Reaction mechanism determines NMDA receptor response to repetitive stimulation. Nature. 2004; 430(7001).
- Popescu G, Auerbach A. The NMDA receptor gating machine: lessons from single channels. Neuroscientist. 2004; 10(3).
- Popescu G, Auerbach A. Modal gating of NMDA receptors and the shape of their synaptic response.. Nature Neuroscience. 2003.
- Peng H, Myers J, Fang X, Stachowiak EK, Maher PA, Martins GG, Popescu G, Berezney R, Stachowiak MK. Integrative nuclear FGFR1 signaling (INFS) pathway mediates activation of the tyrosine hydroxylase gene by angiotensin II, depolarization and protein kinase C. J Neurochem. 2002; 81(3).
- Popescu G, Napoli JL. Analysis of rat cytosolic 9-cis-retinol dehydrogenase activity and enzymatic characterization of rat ADHII. Biochim Biophys Acta. 2000; 1476(1).
- Chai X, Zhai Y, Popescu G, Napoli JL. Cloning of a cDNA for a second retinol dehydrogenase type II. Expression of its mRNA relative to type I. J Biol Chem. 1995; 270(47).
Professional Memberships:
- ASBMB, American Society for Biochemistry and Molecular Biology (2014–present)
- AAMC, American Association of Medical Colleges (2012–present)
- ASPET, America Society for Pharmacology and Experimental Therapeutics (2012–present)
- IBRO, International Brain Research Organization (2000–present)
- SfN, Society for Neuroscience (1999–present)
- BPS, Biophysical Society (1999–present)
- AAAS, American Association for the Advancement of Science (1999–present)
- UBAA, UB Alumni Association
Presentations:
- "The place of PhDs in the medical centers of tommorrow" AAMC CFAS Spring Conference, AAMC, CFAS (2017)
- "Glycinergic Excitatory Receptors" University of Washington, Physiology, University of Washington (2016)
- "Glycinergic excitatory receptors: NMDA receptors in name only" GRC/Excitatory Transmission in Brain Function (2016)
- "Mechanisms in NMDA receptor signaling" Johns Hopkins University, Physiology, Physiology (2015)
- "Why Support Basic Research" AAMC Annual Meeting, AAMC (2015)
- "NMDA Receptors: learning from singles" Harvard University, Mol Cel Biol (2015)
- "Participation in Faculty Governance" AAMC/Spring CFAS Meeting, AAMC (2015)
- "Glycinergic NMDA receptors" Biophysical Society Annual Meeting, Biophysical Society, 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" GRC/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:
- Jacobs School of Medicine & Biomedical Sciences Admissions Committee; Member (2017–2020)
- Faculty Senate; School Representative (2013–2017)
- Faculty Senate Executive Committee; Member (2013–2017)
- AAMC, Board of Directors; Member (2017–2023)
- AAMC, Council of Faculty and Academic Societies; Chair (2017–2023)
- JSMBS Faculty Council, Basic Science Representative; Member (2016–2018)
- Biophysical Society, Committee on Professional Opportunities for Women (CPOW); Chair (2015–2018)
- Biophysical Society, Council; Councilor (2015–2018)
- NIH/NTRC Study Section; Member (2014–2020)
- Faculty Council, Steering Committee on Tenure and Promotions; Member (2014–2017)
- Journal of Neurochemistry; Editorial Board Member (2013–2016)
- AAMC, CFAS Administrative Board; Member (2013–2016)
- Biochemistry, Graduate Affairs Committee; Director (2013–2014)
- MSTP, Admissions Committee; Member (2012–2018)
- Biophysical Society, Career Conversations; Panel Member (2012)
- Biophysical Society, Committee on Professional Opportunities for Women (CPOW); Member (2011–2015)
- PPBS, Steering Committee; Member (2010–2012)
- Society for Neuroscience, Buffalo Chapter; President (2009–2010)
- Biochemistry, Seminar Program; Coordinator (2007–2008)
- UB Postdoctoral Education, Steering Committee; Member (2005–2008)