David H. Farb, Ph.D.

DAVID H. FARB, Ph.D.

Professor and Chairman
Department of Pharmacology & Experimental Therapeutics

Ph.D.: Brandeis University

Lab Page: Laboratory of Molecular Neurobiology

David H. Farb was appointed Professor and Chairman of the Department of Pharmacology & Experimental Therapeutics at Boston University School of Medicine in 1990. Dr. Farb is also Director of the university-wide NIGMS training program in Biomolecular Pharmacology. He has also served as a member of the Drug Development Work Group of Mass Insight, co-author of the Massachusetts Technology Road Map for Drug Discovery, and a consultant for a number of small to large pharmaceutical, biotechnology, and patent litigation companies. He is regularly interviewed by local, national and international media.

As head of the Laboratory of Molecular Neurobiology, he focuses on the identification of pharmacological treatments for mental disorders of learning and memory. His research integrates existing electrophysiological, behavioral, pharmacological, and molecular genetic technologies in a novel systems-level platform for assessing the impact of cognitive enhancers such as neuroactive steroids upon fundamental hippocampal systems for pattern separation (encoding), and pattern completion (retrieval) that are believed to be essential for cognition in all mammals, including man. Deficits in aspects of episodic memory dependent on hippocampal function are evident in a variety of mental disorders, including schizophrenia, autism, Alzheimer’s Disease, and normal aging. Existing pharmacotherapies are limited and carry substantial risk of adverse effects. In search of new approaches for discovery, high-density electrophysiological recordings in awake behaving rats are being used to identify deficits in hippocampal function that underlie cognitive deficits exhibited by aged animals and animals reared in social isolation, the latter being a model for environmental stress during development. Drug delivery via nanoparticles encapsulating hydrophilic or hydrophobic molecules are being engineered for delivery across the blood brain barrier. Nanoparticle composition is being tailored to better deliver drug to specific target sites. Neuroactive drugs and proteins, biomarkers for novel diagnostics, sensitive dyes for neural mapping, and many other applications are envisioned. The major advantage of this technique is the noninvasive delivery of molecules to the CNS via a peripheral injection.

A multidisciplinary approach that includes the techniques of neurophysiology, molecular biology, patch-clamp electrophysiology, cell biology, and molecular neuroanatomy are combined to elucidate the mechanisms and modalities of cognitive enhancers and the discovery of therapeutic treatments for disorders or diseases of the nervous system.

Professional Background

Prior to joining BU, Dr. Farb was a Fogarty Senior International Fellow (1989 – 1990) with Sydney Brenner, PhD in the Molecular Genetics Unit at the Medical Research Council, Cambridge University, UK. Dr. Farb received his B.A. in Chemistry from Long Island University, where he was President of the American Chemical Society chapter and received honors including the American Institute of Chemists Award. He received the Ph.D. in Biochemistry (enzyme mechanisms/bioorganic chemistry) with William P. Jencks, M.D. at Brandeis University. After completing postdoctoral fellowships at Harvard Medical School in Pharmacology with Gerald D. Fischbach, M.D. and in Physiology with Susan E. Leeman, Ph.D., he became Assistant Professor of Anatomy and Cell Biology at the SUNY Downstate Medical Center. Dr. Farb was promoted to full professor with tenure, Head of the Molecular Pharmacology Research Program, and elected Presiding Officer of the Graduate School at SUNY. While in New York, Dr. Farb was elected Chair of the Section of Biological Sciences at the New York Academy of Sciences, where he subsequently founded the Section of Neuroscience. Dr. Farb has served as a consultant to large and small pharmaceutical companies, intellectual property law and portfolio investment firms. Dr. Farb was a member of the founding Scientific Advisory Boards of CoCensys and DOV Pharmaceuticals. He holds 9 issued U.S. patents, one patent issued in Australia, and one issued in Japan. Dr. Farb pioneered development of technology for high throughput electrophysiology and was the Scientific Founder of Scion Pharmaceuticals (acquired by Wyeth), which commercialized his patents on high throughput electrophysiology and small molecule modulators of amino acid receptors. High throughput electrophysiology is currently in use throughout the pharmaceutical industry for ion channel and receptor directed drug discovery.

As a postdoctoral fellow, Dr. Farb, in collaboration with Dr. Dennis W. Choi and Dr. Gerald D. Fischbach, co-discovered the cellular mechanisms of action of benzodiazepines—the class of anxiolytics, sedative hypnotics, and anticonvulsants that includes trade-name drugs such as Xanax, Valium, and Versed. This research showed that benzodiazepines acted by positive allosteric modulation of the type-A GABA receptor (Nature (1977) 269: 342-344). Dr. Farb’s research program focused on the turnover and regulation of GABA receptor function (Science (1984) 226: 857) as a nexus for the control of nervous system function. Dr. Farb’s current research is directed toward the discovery and development of neuromodulators as therapeutic agents and on the structure, function, and cellular dynamics of ion channels and receptors in the brain and spinal cord. Ongoing studies are directed toward understanding the mechanisms of action of abused substances and steroid modulators (Science Signaling (2000) 60: PE1) and their interactions with excitatory and inhibitory amino acid receptors in the central nervous system. Recently, Dr. Farb’s laboratory demonstrated that pregnanolone hemisuccinate inhibits reinstatement of cocaine seeking behavior, and this compound has been selected by NIDA for preclinical development in its Medications Development Program (PNAS (1997) 94: 10450; PNAS (2004) 101: 8198).

Recent News

Selected Publications

Farb DH (2013). An interview with David H Farb, Section Editor for Basic Pharmacology. BMC Pharmacology and Toxicology 2013 August; 14(42). [Abstract]

Saha S, Hu, Martin SC, Bandyopadhyay S, Russek SJ, Farb DH (2013). Polycomblike protein PHF1b: a transcriptional sensor for GABA receptor activity. BMC Pharmacology and Toxicology 2013 August; 14(37). [Abstract]

Kostakis E, Smith C, Jang M-K, Martin SC, Richards KG, Russek SJ, Gibbs TT, Farb DH (2013). The Neuroactive Steroid Pregnenolone Sulfate Stimulates Trafficking of Functional NMDA Receptors to the Cell Surface via a Non-Canonical G-Protein and Ca++ Dependent Mechanism. Molecular Pharmacology 2013 May; 83(6). [Abstract]

Kim JH, Roberts DS, Hu Y, Lau GC, Brooks-Kayal AR, Farb DH, Russek SJ (2011) Brain-derived Neurotrophic Factor Uses CREB and Egr3 to Regulate NMDA Receptor Levels in Cortical Neurons. J Neurochem 2012 Jan; 120(2):210-9. [Abstract]

Kostakis E, Jang M-K, Russek SJ, Gibbs TT, Farb DH (2011) A steroid modulatory domain in NR2A collaborates with NR1 exon-5 to control NMDAR modulation by pregnenolone sulfate and protons. J Neurochem 2011 Nov; 119(3): 486-96. [Abstract]

Desbiens S, Farb DH (2011) Medicine and Pathology – Current Needs for New Therapeutic Agents and Discovery Strategies – A Systems Pharmacology Approach. In: Development of Therapeutic Agents (Shayne Gad, Ed.) John Wiley & Sons. [Abstract]

Desbiens S, Farb DH (2010) Current Needs for New Therapeutic Agents and Discovery Strategies – A Systems Pharmacology Approach. In Pharmaceutical Sciences Encyclopedia: Drug Discovery, Development, and Manufacturing (Shayne Gad, Ed.) John Wiley & Sons. [Abstract]

Eagleson KL, Gravielle MC, Schlueter McFadyen-Ketchumm LJ, Russek SJ, Farb DH, Levitt P (2010) Genetic disruption of the autism spectrum disorder risk gene PLAUR induces GABAA receptor subunit changes. Neuroscience 2010 Jul 14; 168(3):797-810. PMC 2880553. [Article]

Kim JH, Farb DH, Russek SJ (2009) Promoter. Encyclopedia of Neuroscience. U. Windhorst, M.D. Binder, N. Hirokawa, and M.C. Hirsch, Editors. Springer Publishing, Heidelberg, Germany. Part 16, pp. 3291 – 3294.

Berezhnoy D, Gibbs TT, Farb DH (2009) Docking of 1,4-benzodiazepines in the alpha1/gamma2 GABA(A) receptor modulator site. Mol Pharmacol 2009 Aug; 76(2):440-50. PMC 2713131. [Article]

Sadri-Vakili G, Janis GC, Pierce RC, Gibbs TT, Farb DH (2008) Nanomolar Concentrations of Pregnenolone Sulfate Enhance Striatal Dopamine Overflow In Vivo. J Pharmacol Ex Ther 2008 Dec; 327(3): 840-5. PMC 2864155. [Article]

Whittaker MT, Gibbs TT, Farb DH (2008) Pregnenolone sulfate induces NMDA receptor dependent release of dopamine from synaptic terminals in the striatum. J Neurochem. 2008 Oct; 107 (2): 510-21. PMC 2752275. [Press Release]

Berezhnoy D*, Gravielle MC*, Downing S, Kostakis E, Basile AS, Skolnick P, Gibbs TT, Farb DH (2008) Pharmacological Properties of DOV 315,090, an ocinaplon metabolite. BMC Pharmacology, Jun 13; 8:11 (equal contributions: *). PMC 2529273. [Article]

Hu Y, Lund IV, Gravielle MC, Farb DH, Brooks-Kayal AR, Russek SJ (2008) Surface expression of GABA(A) receptors is transcriptionally controlled by the interplay of CREB and its binding partner ICER. J. Biol. Chem. Apr 4; 283 (14):9328-40. Jan 7; Epub 2008 Jan 7. PMC 2431045. [Article]

Berezhnoy D, Gravielle V, Farb DH (2007) Pharmacology of the GABAA Receptor, In: Handbook of Contemporary Neuropharmacology (David Sibley, Michael Kuhar, Israel Hanin, and Phil Skolnick, Eds.) John Wiley & Sons.

Farb DH, Steiger JL, Martin SC, Gravielle MC, Gibbs TT, Russek SJ (2007) Mechanisms of GABAA and GABAB Receptor Gene Expression In: The GABA Receptors (Sam Enna and Hans Mohler, Eds.) Humana Press.

Gibbs TT, Russek SJ, Farb DH. Sulfated steroids as endogenous neuromodulators. Pharmacol Biochem Behav. 2006 Aug;84(4):555-67. Epub 2006 Oct 4. [Abstract]

Popik P, Kostakis E, Krawczyk M, Nowak G, Szewczyk B, Krieter P, Chen Z, Russek SJ, Gibbs TT, Farb DH, Skolnick P, Lippa AS, Basile AS. The anxioselective agent 7-(2-chloropyridin-4-yl)pyrazolo-[1,5-a]-pyrimidin-3-yl](pyridin-2-yl)methan one (DOV 51892) is more efficacious than diazepam at enhancing GABA-gated currents at alpha1 subunit-containing GABAA receptors. J Pharmacol Exp Ther. 2006 Dec;319(3):1244-52. Epub 2006 Sep 13. [Abstract]

Downing SS, Lee YT, Farb DH, Gibbs TT. Benzodiazepine modulation of partial agonist efficacy and spontaneously active GABA(A) receptors supports an allosteric model of modulation. Br J Pharmacol. 2005 Aug;145(7):894-906. [Abstract]

Lippa A, Czobor P, Stark J, Beer B, Kostakis E, Gravielle M, Bandyopadhyay S, Russek SJ, Gibbs TT, Farb DH, Skolnick P. (2005) Selective anxiolysis produced by ocinaplon, a GABA(A) receptor modulator. Proc Natl Acad Sci U S A. 2005 May 17;102(20):7380-5. [Abstract]

Gravielle MC, Faris R, Russek SJ, Farb DH. (2005) GABA induces activity dependent delayed-onset uncoupling of GABA/benzodiazepine site interactions in neocortical neurons. J Biol Chem. 2005 Jun 3;280(22):20954-60. [Abstract]

Steiger JL, Bandyopadhyay S, Farb DH, Russek SJ. (2004) cAMP response element-binding protein, activating transcription factor-4, and upstream stimulatory factor differentially control hippocampal GABABR1a and GABABR1b subunit gene expression through alternative promoters. J Neurosci. 2004 Jul 7;24(27):6115-26. [Abstract]

Jang MK, Mierke DF, Russek SJ, Farb DH. (2004) A steroid modulatory domain on NR2B controls N-methyl-D-aspartate receptor proton sensitivity. Proc Natl Acad Sci U S A. 2004 May 25;101(21):8198-203. [Abstract]

Martin SC, Steiger JL, Gravielle MC, Lyons HR, Russek SJ, Farb DH. (2004) Differential expression of gamma-aminobutyric acid type B receptor subunit mRNAs in the developing nervous system and receptor coupling to adenylyl cyclase in embryonic neurons. J Comp Neurol. 2004 May 17;473(1):16-29. [Abstract]

Steiger JL, Alexander MJ, Galler JR, Farb DH, Russek SJ. (2004) Effects of prenatal malnutrition on GABAA receptor alpha1, alpha3 and beta2 mRNA levels. Neuroreport. 2003 Sep 15;14(13):1731-5. [Abstract]

Sadri-Vakili G, Johnson DW, Janis GC, Gibbs TT, Pierce RC, Farb DH. (2003) Inhibition of NMDA-induced striatal dopamine release and behavioral activation by the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one hemisuccinate. J Neurochem. 2003 Jul;86(1):92-101. [Abstract]

Steiger JL, Galler JR, Farb DH, Russek SJ. (2002) Prenatal protein malnutrition reduces beta(2), beta(3) and gamma(2L) GABA(A) receptor subunit mRNAs in the adult septum. Eur J Pharmacol. 2002 Jun 20;446(1-3):201-2. [Abstract]

Malayev A, Gibbs TT, Farb DH. (2002) Inhibition of the NMDA response by pregnenolone sulphate reveals subtype selective modulation of NMDA receptors by sulphated steroids. Br J Pharmacol. 2002 Feb;135(4):901-9. [Abstract]

Martin SC, Russek SJ, Farb DH. (2001) Human GABA(B)R genomic structure: evidence for splice variants in GABA(B)R1 but not GABA(B)R2. Gene. 2001 Oct 31;278(1-2):63-79. [Abstract]

Lyons HR, Land MB, Gibbs TT, Farb DH. (2001) Distinct signal transduction pathways for GABA-induced GABA(A) receptor down-regulation and uncoupling in neuronal culture: a role for voltage-gated calcium channels. J Neurochem. 2001 Sep;78(5):1114-26. [Abstract]

Gibbs TT, Farb DH. (2000) Dueling enigmas: neurosteroids and sigma receptors in the limelight. Science Signaling 2000 Nov 28;2000(60):PE1. Review. [Abstract]

Russek SJ, Bandyopadhyay S, Farb DH. (2000) An initiator element mediates autologous downregulation of the human type A gamma -aminobutyric acid receptor beta 1 subunit gene. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8600-5. [ Abstract ]

Weaver CE, Land MB, Purdy RH, Richards KG, Gibbs TT, Farb DH. (2000) Geometry and charge determine pharmacological effects of steroids on N-methyl-D-aspartate receptor-induced Ca(2+) accumulation and cell death. J Pharmacol Exp Ther. 2000 Jun;293(3):747-54. [ Abstract ]

McLean PJ, Shpektor D, Bandyopadhyay S, Russek SJ, Farb DH. (2000) A minimal promoter for the GABA(A) receptor alpha6-subunit gene controls tissue specificity. J Neurochem. 2000 May;74(5):1858-69. [ Abstract ]

Lyons HR, Gibbs TT, Farb DH. (2000) Turnover and down-regulation of GABA(A) receptor alpha1, beta2S, and gamma1 subunit mRNAs by neurons in culture. J Neurochem. 2000 Mar;74(3):1041-8. [ Abstract ]

Park-Chung M, Malayev A, Purdy RH, Gibbs TT, Farb DH. (1999) Sulfated and unsulfated steroids modulate gamma-aminobutyric acidA receptor function through distinct sites. Brain Res. 1999 May 29;830(1):72-87. [ Abstract ]

Martin SC, Russek SJ, Farb DH. (1999) Molecular identification of the human GABABR2: cell surface expression and coupling to adenylyl cyclase in the absence of GABABR1. Mol Cell Neurosci. 1999 Mar;13(3):180-91. [ Abstract ]

Weaver CE Jr, Wu FS, Gibbs TT, Farb DH. (1998) Pregnenolone sulfate exacerbates NMDA-induced death of hippocampal neurons. Brain Res. 1998 Aug 24;803(1-2):129-36. [ Abstract ]

Yaghoubi N, Malayev A, Russek SJ, Gibbs TT, Farb DH. (1998) Neurosteroid modulation of recombinant ionotropic glutamate receptors. Brain Res. 1998 Aug 24;803(1-2):153-60. [ Abstract ]

Park-Chung M, Wu FS, Purdy RH, Malayev AA, Gibbs TT, Farb DH. (1997) Distinct sites for inverse modulation of N-methyl-D-aspartate receptors by sulfated steroids. Mol Pharmacol. 1997 Dec;52(6):1113-23. [ Abstract ]

Weaver CE Jr, Marek P, Park-Chung M, Tam SW, Farb DH. (1997) Neuroprotective activity of a new class of steroidal inhibitors of the N-methyl-D-aspartate receptor. Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10450-4. [ Abstract ]

Weaver CE Jr, Park-Chung M, Gibbs TT, Farb DH. (1997) 17beta-Estradiol protects against NMDA-induced excitotoxicity by direct inhibition of NMDA receptors. Brain Res. 1997 Jul 4;761(2):338-41. [ Abstract ]

Publication Search via PubMed

Patents

Modulation of receptor-mediated ion transport

May 18, 1993
Patent: 5,212,167
Inventors: Farb, David H.

Abstract

The subject application discloses methods for modulating NMDA-mediated ion transport, and inhibiting non-NMDA glutamate-induced ion transport, in neuronal cells. The methods involve contacting a neuronal cell with an effective amount of the neurosteroid pregnenolone sulfate, or pharmacologically effective derivatives thereof.

Modulation of receptor-mediated ion transport

November 22, 1994
Patent: 5,366,968
Inventors: Farb, David H.

Abstract

The subject application discloses methods for modulating NMDA-mediated ion transport, and inhibiting non-NMDA glutamate-induced ion transport, in neuronal cells. The methods involve contacting a neuronal cell with an effective amount of the neurosteroid pregnenolone sulfate, or pharmacologically effective derivatives thereof.

Inhibition of NMDA receptor activity and modulation of glutamate-mediated synaptic activity

March 30, 1999
Patent: 5,888,996
Inventors: Farb, David H.

Abstract

The present invention relates to a method of inhibiting N-methyl-D-aspartate (NMDA) glutamate receptor-mediated ion channel activity (NMDA receptor activity), comprising contacting a neuronal cell (e.g., hippocampal neuron, spinal cord cell) with an effective amount (e.g., 1 to 500 mu.M) of a derivative of pregnenolone sulfate. Derivatives of pregnenolone sulfate that inhibit NMDA receptor activity include pregnenolone sulfate in which the A ring includes at least one double bond or is fully unsaturated, the double bond at the C5-C6 position is reduced, the moiety at the C3, C10, C11 or C13 position is modified, alone or in combination. It further relates to pregnenolone sulfate derivatives which have modifications at other positions (e.g., C5, C7, C10, C16, C17, C18, C19, C20, C21), alone or in combination, and are inhibitors of NMDA receptor activity. The pregnenolone sulfate derivatives differ from pregnenolone sulfate at least one position. The present invention also relates to a method of modulating or altering (e.g., potentiating; inhibiting) excitatory glutamate-mediated synaptic activity comprising contacting neurons with pregnenolone sulfate and derivatives of pregnenolone sulfate.

Cellular physiology workstations for automated data acquisition and perfusion control

April 11, 2000
Patent: 6,048,722
Inventors: Farb, David H.; Yaghoubi; Nader; Gibbs; Terrell T.

Abstract

Cellular physiology workstations for automated data acquisition and perfusion control are described. The cellular physiology workstation may be used for physiological and electrophysiological experiments. Methods for employing such cellular physiology workstations in physiological and electrophysiological experiments are also disclosed. The cellular physiology workstations comprise one or more recording chambers each for holding one or more cells to be measured. One or more cells are place in each recording chamber. Perfusion device, such as an automatic perfusion system is connected to the recording chamber to perfuse the cells with a plurality of solutions containing different concentration of one or more agents to be tested. Biosensors, such as patch clamps, electrodes, or microscopes are positioned to detect a response from the cell. The cellular physiology workstation may optionally comprise injecting device for introducing an injection solution into the cell before and during analysis.

Neuron-specific transcriptional promoter

May 23, 2000
Patent: 6,066,726
Inventors: Farb, David H. (Cambridge, MA); Russek; Shelley J.

Abstract

The 5′-flanking region and core regulatory domains that underlie neuronal specific expression of the human .gamma.-aminobutyric acid type A (GABA.sub.A) receptor .beta.1 subunit gene are identified herein. Sequence analysis, mapping of transcriptional initiation sites, and transfection of reporter gene constructs into primary cultures demonstrate that neuronal and region specific activity resides in a TATA-less minimal promoter of 186 bp, comprising an initiator, the major transcriptional start site, a presumptive TFIID binding site, and an enhancer. Enhancer sequence contained within a 26 bp region at the 5′-end of the minimal promoter is essential for activity but not for tissue specificity. Moreover, .beta.1 promoter activity is subject to autologous inhibition, indicating that GABA-induced receptor mRNA downregulation results from an inhibition of gene transcription. Regulation of neurotransmitter receptor gene expression plays an important role in nervous system development and function, and impaired gene regulation may underlie the etiology of certain neurological diseases.

Inhibition of NMDA receptor activity by pregnenolone sulfate derivatives

July 4, 2000
Patent: 6,083,941
Inventors: Farb, David H.

Abstract

The present invention relates to a method of inhibiting N-methyl-D-aspartate (NMDA) glutamate receptor-mediated ion channel activity (NMDA receptor activity), comprising contacting a neuronal cell (e.g., hippocampal neuron, spinal cord cell) with an effective amount (e.g., 1 to 500 mu M) of a derivative of pregnenolone sulfate. Derivatives of pregnenolone sulfate that inhibit NMDA receptor activity include pregnenolone sulfate derivatives in which the A ring includes at least one double bond; PS in which the A ring is fully unsaturated; PS derivatives in which the double bond at the C5-C6 position is reduced; and PS in which the moiety at the C3, C5, C6, C7, C11, C17, C20 and/or C21 position is modified. It further relates to PS derivatives which have modifications at other positions (e.g., C10, C10, C13, C18, C19), alone or in combination, and are inhibitors of NMDA receptor activity. The present invention also relates to a method of modulating or altering (e.g., potentiating; inhibiting) excitatory glutamate-mediated synaptic activity comprising contacting neurons with pregnenolone sulfate and derivatives of pregnenolone sulfate. The present invention also relates to a method of treating a disease associated with L-glutamate-induced NMDA receptor activation selected from the group consisting of: neuropathic pain, drug withdrawal/dependency, epilepsy, glaucoma, chronic neurodegenerative diseases, amyotrophic lateral sclerosis, anxiety disorders, brain cell death, ischemia, stroke, trauma in a host comprising administering to the host an effective amount of a derivative of pregnenolone sulfate.

Cellular physiology workstations for automated data acquisition and perfusion control

July 31, 2001
Patent: 6,268,168
Inventors: Farb, David H.; Yaghoubi; Nader; Gibbs; Terrell T.

Abstract

Cellular physiology workstations for automated data acquisition and perfusion control are described. The cellular physiology workstation may be used for physiological and electrophysiological experiments. Methods for employing such cellular physiology workstations in physiological and electrophysiological experiments are also disclosed. The cellular physiology workstations comprise one or more recording chambers each for holding one or more cells to be measured. One or more cells are place in each recording chamber. Perfusions means, such as an automatic perfusion system is connected to the recording chamber to perfuse the cells with a plurality of solutions containing different concentration of one or more agents to be tested. Biosensors, such as patch clamps, electrodes, or microscopes are positioned to detect a response from the cell. The cellular physiology workstation may optionally comprise injecting means for introducing an injection solution into the cell before and during analysis.

Methods for identifying a subunit specific modulator of N-methyl-D-asparate receptor

September 23, 2003
Patent: 6,623,933
Inventors: Farb, David H.; Yaghoubi, Nader; Russek, Shelley; Jang, Ming-Kuei; Gibbs, Terrell T.

Abstract

Disclosed is a method for identifying a subunit specific modulator of the N-methyl-D-aspartate (NMDA) receptor. The method involves providing a plurality of NMDA receptors which differ in their subunit identity. The receptors are contacted with a neurotransmitter recognition site ligand in the presence and absence of a candidate modulator. Receptor activity is then assayed, with an increase or decrease in activity in at least one, but not all members of the plurality of NMDA receptors, in the presence but not the absence of a candidate modulator, being an indication that the candidate modulator is a subunit specific modulator. The subunit identity of the subset of the NMDA receptors to determine the subunit specificity of the candidate modulator. Various combinations of NMDA receptor subunits are provided.

Cellular physiology workstations for automated data acquisition and perfusion control

July 13, 2004
Patent: 6,762,036
Inventors: Farb, David H.; Yaghoubi; Nader; Gibbs; Terrell T.

Abstract

Cellular physiology workstations for automated data acquisition and perfusion control are described. The cellular physiology workstation may
be used for physiological and electrophysiological experiments. Methods for employing such cellular physiology workstations in physiological and electrophysiological experiments are also disclosed. The cellular physiology workstations comprise one or more recording chambers each for holding one or more cells to be measured. One or more cells are place in each recording chamber. Perfusions means, such as an automatic perfusion syslatem is connected to the recording chamber to perfuse the cells with a plurality of solutions containing different concentration of one or more agents to be tested. Biosensors, such as patch clamps, electrodes, or microscopes are positioned to detect a response from the cell. The cellular physiology workstation may optionally comprise injecting means for introducing an injection solution into the cell before and during analysis.

Effect of steroids on NMDA receptors depends on subunit composition

July 7, 2005
Patent: AU 200070981
Inventors: Farb, David H.; Russek, Shelley J.; Jang, Ming-Kuei; Gibbs,
Terrell T.; Yaghoubi, Nader.

Effect of Steroids on NMDA Receptors Depends on Subunit Composition

March 11, 2009
Patent: EP 1 212 618 B1
Inventors: Farb, David H.; Russek, Shelley J.; Jang, Ming-Kuei; Gibbs,
Terrell; Yaghoubi, Nader.

Inhibition of NMDA Receptor Activity by Pregnenolone Sulfate Derivatives

May 22, 2009
Patent: Japan No. 4313435
Inventors: Farb, David H.

United States Patent Applications

(published since March 15, 2001)

Effect of steroids on NMDA receptors depends on subunit composition

October 14, 2004
20040204490 Kind Code A1
Inventors: Farb, David H.; Russek, Shelley;; Jang, Ming-Kuei; Gibbs, Terrell T.; Yaghoubi, Nader

Abstract

Disclosed is a method for identifying a subunit specific modulator of the N-methyl-D-aspartate (NMDA) receptor. The method involves providing a plurality of NMDA receptors which differ in their subunit identity. The receptors are contacted with a neurotransmitter recognition site ligand in the presence and absence of a candidate modulator. Receptor activity is then assayed, with an increase or decrease in activity in at least one, but not all members of the plurality of NMDA receptors, in the presence but not the absence of a candidate modulator, being an indication that the candidate modulator is a subunit specific modulator. The subunit identity of the subset of the NMDA receptors to determine the subunit specificity of the candidate modulator. Various combinations of NMDA receptor subunits are provided.

Neuroactive steroid derivatives and method of use

April 29, 2004
20040082554 Kind Code A1
Inventors: Farb, David H.; (Brookline, MA) ; Sadri-Vakili, Ghazaleh; (Boston, MA) ; Pierce, Robert Christopher; (Boston, MA) ; Johnson, David W; (Kennebunk, ME); Gibbs, Terrell T

Abstract

The invention relates to neuroactive steroid compounds that are useful in modulating CNS effects, diseases or disease symptoms. The invention also relates to use of the compounds in methods of treating or preventing disease or disease symptoms, and methods of modulating or mediating CNS effects or processes

Cellular physiology workstations for automated data acquisition and perfusion control

June 20, 2002
20020076689 Kind Code A1
Inventors: Farb, David H.; Yaghoubi, Nader; Gibbs, Terrell T

Abstract

Cellular physiology workstations for automated data acquisition and perfusion control are described. The cellular physiology workstation may be used for physiological and electrophysiological experiments. Methods for employing such cellular physiology workstations in physiological and electrophysiological experiments are also disclosed. The cellular physiology workstations comprise one or more recording chambers each for holding one or more cells to be measured. One or more cells are place in each recording chamber. Perfusions means, such as an automatic perfusion system is connected to the recording chamber to perfuse the cells with a plurality of solutions containing different concentration of one or more agents to be tested. Biosensors, such as patch clamps, electrodes, or microscopes are positioned to detect a response from the cell. The cellular physiology workstation may optionally comprise injecting means for introducing an injection solution into the cell before and during analysis.

Cellular physiology workstations for automated data acquisition and perfusion control

September 30, 2004
20040191853 Kind Code A1
Inventors: Farb, David H.; Gibbs, Terrell T.; Yaghoubi, Nader

Abstract

Cellular physiology workstations for automated data acquisition and perfusion control are described. The cellular physiology workstation may be used for physiological and electrophysiological experiments. Methods for employing such cellular physiology workstations in physiological and electrophysiological experiments are also disclosed. The cellular physiology workstations comprise one or more recording chambers each for holding one or more cells to be measured. One or more cells are place in each recording chamber. Perfusions means, such as an automatic perfusion system is connected to the recording chamber to perfuse the cells with a plurality of solutions containing different concentration of one or more agents to be tested. Biosensors, such as patch clamps, electrodes, or microscopes are positioned to detect a response from the cell. The cellular physiology workstation may optionally comprise injecting means for introducing an injection solution into the cell before and during analysis.

Patents Pending (excluding international phase of above issued patents)

A Neural Specific Cytosolic Sulfotransferase for Drug Screening (BU 00-29)

60/229,929
Inventors: Farb, David H.; Martin, Stella C.

Seizure -induced upregulation of the GABRA4 promoter identifies a condition-specific vector for the treatment of epilepsy.

BU04-03
Inventors: Russek, Shelley J; Brooks-Kayal, A; Farb, David H.

Laboratory Alumni: Where They Are Now

Pre-Doctoral Students

Sophie Desbiens, Ph.D. – 2009 (BME)
Thesis: Therapeutic Agents for Cocaine Addiction: A Systems Pharmacology Approach
Position: Senior Consultant, Decision Resources Inc.

Matthew Whitaker, Ph.D. – 2009
Thesis: Pregnenolone Sulfate Modulates Neurotransmitter Release from Isolated Neuron Terminals of the Rat Striatum
Position: Pharmacology/Toxicology Reviewer in the Division of Pulmonary, Allergy, and Rheumatology Products, Center for Drug Evaluation and Review, FDA

Emmanuel Kostakis, M.A., Ph.D. – 2007
MA Thesis: Effect of Neurosteroids on NMDA Receptors Comprising Different Isoforms of the NMDA R1 Subunit
PhD Thesis: Dual Regulation of N-Methyl-D-Aspartate Receptor Function by Neuroactive Steroids
Position: Global Project Manager – Operational Project Management, Merck Serono Geneva, Switzerland

Felicia Tsai, M.A. – 2004
Thesis: Examined the modulatory effects of neurosteroid (Pregnenolone sulfate) on neurotransmitter receptors (NMDA Receptors)
Position: Senior Research Associate/Clinical Research Associate at Arkal Medical

Ming-Kuei Jang, Ph.D. – 2003
Thesis: Molecular Mechanisms for Pregnenolone Sulfate Modulation of the N-Methyl-D-Aspartate Receptor
Position: Institute Associate Director, Institute for Applied Cancer Science at MD Anderson Cancer Center, Houston, TX

Ghazaleh Sadri-Vakili, Ph.D. – 2003
Thesis: Neurosteroids Modulate Ionotrophic Glutamate Receptor-Induced Dopamine Release and Locomotor Activity in Rats
Position: Assistant Professor of Neurology, Harvard Medical School, Massachusetts General Hospital

Ghazaleh Sadri-Vakili, Ph.D. – 2003
Thesis: Neurosteroids Modulate Ionotrophic Glutamate Receptor-Induced Dopamine Release and Locomotor Activity in Rats
Position: Assistant Professor of Neurology, Harvard Medical School, Massachusetts General Hospital

Janine L. Steiger, Ph.D. – 2003 (Co-Advisor)
Thesis: Regulation of GABA Receptor Gene Experssion in the CNS:  A Role for CREB/ATF Transcription Factors and Effects of Prenatal Protein Malnutrition
Position: Director, Discovery Operations at Zalicus Incorporated

Mio Kato, M.A. – 2001
Position: Ph.D. candidate in Health Communication

Garrick Lau, M.D./Ph.D. – 1999 (Co-Advisor)
Thesis:Transcriptional Regulation of the NMDA Receptor Subunit 1 Gene in Rat Neocortical Neurons by the Map Kinase and Cyclic AMP-Dependent Signaling Pathway
Position: Anesthesiologist, Walnut Creek Medical Center, Department of Anesthesia

Martin D. Leach, Ph.D. – 1998
Thesis: Isolation and Characterization of a Promotor for the Human GABA-A Receptor Alpha-1 Subunit Gene
Position: Vice President R&D IT, Biogen Idec

Helen Lyons, Ph.D. – 1998
Thesis: Agonist-Induced GABA A Receptor Down-Regulation and Uncoupling in Neuronal Culture: Multiple Signal Transduction Pathways and a Role for Intracellular Calcium
Position: Research Scientist II, IDEXX

Pamela J. McLean, Ph.D. – 1998
Thesis: Regulation and Chromosomal Localization of GABA-A Receptor Alpha-Subunit Genes, GABRA6 and GABRA 4
Position: Senior Associate Consultant and PI , Mayo Clinic, Jacksonville, FL

Charles E. Weaver Jr., M.D./Ph.D. – 1998
Thesis: Steroid Modulation of NMDA-Inducwed Death of Rat Hippocampal Neurons in Primary Cell Culture
Position: Neurosurgeon at Spectrum Neurosurgical Specialists, P.C.

Nader Yaghoubi, M.D./Ph.D. – 1998
Thesis: Modulation of Recombinant Glutamate Receptors of Neuroactive Steroids Studied Using an Automated Workstation for Oocyte Electrophysiology
Position: CEO at Symbiotix Biotherapies, Inc.

Mijeong Chung, Ph.D. – 1997
Thesis: Steroids as Functional Modulators of Amino Acids Receptors
Position: Senior Scientist, Institute of Bioscience and Biotechnology, Taejon, Korea

Yan Tony Lee, M.A. – 1997
Thesis: Partial GABA A Agonists and the Testing of a Two-State Model of GABA A Receptor Modulatio
Position:

Diana Shpektor, M.A. – 1997
Thesis: Ethanol Modulation of GABA A Receptor Functoin Regulates Subunit-Specific Gene Expression
Position: Manager / Senior Associate Scientist at Amgen, Inc.

Shelley J. Russek, M.A., Ph.D. – 1994
Thesis: Molecular Genetics of the GABA A Receptor: Structural Analysis and Autologus Regulation of the Beta Subunit Genes
Position: Professor of Pharmacology, BUSM, and Director, BU Graduate Program for Neuroscience

Dominic Roca, M.D./Ph.D. – 1990
Position: Pulmonologist

James Celentano, M.D./Ph.D. – 1987
Position: Emergency Medicine, Columbia University Medical Center

Daniel Mierlak, M.D./Ph.D. – 1987
Position: Psychiatrist

Cynthia Czajkowski, Ph.D. – 1987
Position: Vilas Distinguished Professor, Department of Neuroscience, University of Wisconsin – Madison

Laurence A. Borden, Ph.D. – 1985
Position: Scientific Advisor, Kaye, Scholer, FIerman, Hayes & Handler, LLP, New York, New York

 

Post-Doctoral Fellows

Loren J. Martin, Ph.D. – 2009-2010
Position: Postdoctoral Research Scientist, Pain Genetics Lab, University of Toronto

Jonathan Robitsek, Ph.D. – 2008-
Position: Neuroscientist, New York City

Scott Downing, Ph.D. – 2005-
Position: Bioinformatics Research Scientist, Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine

Marcia H. Ratner, Ph.D. – 2004-
Position: Project Manager, Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine

Stella Martin, Ph.D. – 1997-
Position: Postdoctoral Research Scientist, Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine

Sophie Desbiens, Ph.D. – 2009-2010
Position: Senior Consultant, Decision Resources Inc.

Dmytro Berezhnoy, Ph.D. – 2005-2009
Position: VP of Portfolio Strategy and BD&L at Ogenx Therapeutics

Dmytro Berezhnoy, Ph.D. – 2005-2009
Position: VP of Portfolio Strategy and BD&L at Ogenx Therapeutics

Dario Dieguez, Ph.D. – 2006-2008
Position: Senior Research Program Manager & Science Writer at Lupus Foundation of America, Inc.

Emmanuel Kostakis, M.A., Ph.D. – 2005-2008
Position: Global Project Manager – Operational Project Management, Merck Serono Geneva, Switzerland

Janine L. Steiger, Ph.D. – 2003-2006
Position: Director, Discovery Operations at Zalicus Incorporated

Hui Zhong, M.D./Ph.D. – 2001-2003
Position: Associate Professor of Microbiology, Immunology and Cancer Biology, University of Virginia

Weimin Dai, M.D./Ph.D. – 1998
Position: General Manager, UT (Shanghai) Pharma

Shamol Saha, Ph.D. – 2000-2005
Position: Senior Research Scientist, Boston University School of Medicine

Helen Lyons, Ph.D. – 1998-2001
Position: Research Scientist II, IDEXX

Valerie Itier, Ph.D. – 1997-1999
Position: Neurophysicist, INSERM

Andrew Malayev, Ph.D. – 1996-1999
Position:

Qiang Wang, Ph.D. – 1989-1992
Position:
Associate Professor, Department of Chemical and Biological Engineering, Colorado State University

Lois Rabow, Ph.D. – 1989-1992
Position:

Fong-Sen Wu, Ph.D. – 1988-1992
Position:
Associate Professor, National Cheng Kung University, Taiwan

Linda K. Friedman, Ph.D. – 1988-1990
Position:
Associate Professor, New Jersey Neuroscience Institute

Mark Farrant, Ph.D. – 1987-1989
Position:
Professor of Neuroscience, University College London

Sue Yin, Ph.D. – 1986-1987
Position:
Associate Professor, National Taiwan University, Taiwan

Kenneth J. Rhodes, Ph.D. – 1986-1991
Position:
Vice President, Discovery Neurobiology, Biogen Idec

Laurence A. Borden, Ph.D. – 1985-1987
Position:

Thomas R. Tobin, Ph.D. – 1985-1986
Position:

Grant D. Schiller, Ph.D. – 1982-1986
Position:

Terrell T. Gibbs, Ph.D. – 1980-1982
Position:
Associate Professor, Department of Pharmacology, Boston University School of Medicine

Christopher Y. Chan, Ph.D. – 1980-1982
Position: Assistant Medical Professor, Physiology and Pharmacology, School of Biomedical Education, The City College of New York

Contact

Office: L-603
Phone: 617-638-4300
Fax: 617-638-4329
Lab Phone: 617-638-5323
Email: dfarb at bu.edu