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BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Michael S. Gold, PhD Professor eRA COMMONS USER NAME msg001 EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION DEGREE (if applicable) YEAR(s) University of California at Berkeley, Berkeley, CA University of California at Los Angeles, L A, CA University of California at San Francisco, S F, CA University of California at Los Angeles, L A, CA BA PhD (Post-doc) (Post-doc) 05/1987 06/1994 1994-1995 1996-1997 FIELD OF STUDY Psychology Neuroscience Neuroscience Neuroscience A. Personal Statement Pain continues to be a major health problem with tremendous financial, social and psychological costs. Conservative estimates put the cost of pain to the US economy well into the hundreds of billions of dollars per year as a result of associated medical expenses and lost wages with a significant minority of Americans suffering from persistent or recurrent pain syndromes throughout the most productive years of their lives. Just one pain syndrome, migraine headache, directly impacts 20% of the adult population. Yet, there remain few if any effective therapies devoid of serious side effects that are currently available to treat pain, particularly persistent or recurrent pain associated with syndromes. The clinical features of a number of pain syndromes serve as the organizing focus of research in the Gold laboratory. These observations include the following: 1) many pain syndromes are unique to a particular part of the body such as the head in migraine, the temporomandibular joint in temporomandibular disorder (TMD), or the colon in inflammatory bowel disease (IBD); 2) many pain syndromes such as migraine, TMD and IBD occur with a greater prevalence, severity and/or duration in women than in men; 3) many pain syndromes are associated with changes in the excitability of primary afferent neurons; 4) there are time dependent changes in the mechanisms underlying pain syndromes; and 5) the type of injury, (i.e., inflammation or nerve injury), are differentially sensitive to therapeutic interventions. These observations led to specific hypotheses that are tested in ongoing studies in the Gold laboratory. These include 1) characterizing the mechanisms underlying inflammation-induced changes in the evoked Ca2+ transients in sensory neurons, 2) characterizing the mechanisms underlying the inflammatory mediator-induced sensitization of dural afferents, 3) characterizing the influence of estrogen on the excitability of spinal and trigeminal ganglion neurons, 4) characterizing the mechanisms underlying the link between stress and migraine, 5) characterizing the role of changes in inhibitory receptors, in particular GABA, in injury-induced increases in sensitivity, and 6) identification of ways to maximize the therapeutic utility of local anesthetics. The ultimate goal of these studies is to identify novel targets for the development of therapeutic interventions for the treatment of pain. B. Positions and Honors Employment Experience: Department of Oral and Maxillofacial Surgery 9/94-12/95 University of California, San Francisco, San Francisco, CA Post-Doctoral Fellow in the laboratory of Jon. D. Levine, M.D., Ph. D. Departments of Anesthesiology and Physiology 1/96-2/97 University of California, Los Angeles, Los Angeles, CA Post-Doctoral Fellow in the laboratories of Drs. F. Bezanilla and A-M. Correa. Department of Oral & Craniofacial Biological Sciences University of Maryland at Baltimore, Baltimore, MD Research Assistant Professor 1/98 - 7/98 Department of Oral & Craniofacial Biological Sciences University of Maryland at Baltimore, Baltimore, MD Assistant Professor 7/98 – 5/03 Department of Biomedical Sciences University of Maryland at Baltimore, Baltimore, MD Associate Professor 5/03 – 9/06 Department of Medicine Division of Gastroenterology University of Pittsburgh School of Medicine, Pittsburgh, PA Visiting Associate Professor 10/06 – 7/08 Department of Anesthesiology University of Pittsburgh School of Medicine, Pittsburgh, PA Associate Professor 8/08 – 12/10 Department of Anesthesiology University of Pittsburgh School of Medicine, Pittsburgh, PA Professor 1/11 – Honors and Awards: NIH Postdoctoral Fellowship in Neurology Bank of America/Giannini Foundation Scholarship American Pain Society's Early Career Achievement Award Associate Editor for the journal Pain Regular member of NIH Study Section NST-2 Associate Editor for Brain Research Director at Large, American Pain Society Editorial Board for the Journal of Pain Faculty of 1000 in Medicine Associate Editor for the Journal of Neuroscience Regular member of NIH Study Section SCS Reviewing Editor for the Journal of Neuroscience 9/94-7/97 8/97-12/97 4/01 2000 – 2009 2005 – 2009 2006 – 2010 2006 – 2007 2007 – present 2008 – present 2008 – 2009 2009 – 2011 2009 – present C. Publications: 15 from a total of 87 journal articles, reviews and book chapters Gold MS, Reichling DB, Shuster MJ and Levine JD (1996) Hyperalgesic agents increase a TTX-resistant Na+ current in nociceptors. Proc. Nat’l. Acad. Sci. (USA), 93 (3): 1108-1112 (PMCID: PMC40039) Gold MS, Levine JD and Correa AM (1998) Modulation of TTX-R INa by PKC and PKA and their role in PGE2induced sensitization of rat sensory neurons in vitro. J. Neurosci. 18(24): 10345-10355 (PMID: 9852572) Gold MS, and Thut PD (2001) Lithium increases potency of lidocaine-induced block of voltage-gated Na(+) currents in rat sensory neurons in vitro. J Pharmacol Exp Ther 299:705-711. Gold MS, Weinreich D, Kim S-K, Wang R, Porreca F and Lai J (2003) Redistribution of TTX-Resistant Sodium Channels Mediates Neuopathic Pain. J. Neurosci. 23 (1): 158-166 (PMID: 12514212) Harriott AM, and Gold MS (2008) Serotonin type 1D receptors (5HT1DR) are differentially distributed in nerve fibers innervating craniofacial tissues. Cephelalgia 28(9): 933-944 (PMCID: PMC2682350) Hermanstyne TO, Markowitz K, and Gold MS, (2008) Mechanotransducers in rat pulpal afferents. J Dent Res. 87(9): 834-838 (PMCID: PMC2577312) Warren C, Mok L, Gordon S, Fouad AF, and Gold MS (2008) Quantification of neural protein in extirpated tooth pulp. J Endo 34 (1): 7-10 (PMCID: PMC2176084) Harriott AM, and Gold MS. (2009) Electrophysiological properties of dural afferents in the absence and presence of inflammatory mediators. J Neurophysiol 101(6): 3126-3134 (PMCID: PMC2694126) Zhang X-L., Mok L, Katz, EJ, and Gold MS, (2010) BKCa currents are enriched in a subpopulation of adult rat cutaneous dorsal root ganglion neurons. Eur. J. Neurosci. 31(3): 450-462 (PMCID: PMC2843514) Vaughn (Harriott) AM, and Gold MS (2010) Ionic mechanisms underlying inflammatory mediator-induced sensitization of dural afferents J Neurosci 30(23): 7878-7888 (PMCID: PMC2900838) Lu S-G, Zhang X-L, Luo ZD, and Gold MS (2010) Persistent Inflammation Alters the Density and Distribution of Voltage-Activated Calcium Channels in Subpopulations of Rat Cutaneous DRG neurons. Pain 151(3): 633-643 (PMCID: PMC2978671) Boegel K Gyulai FE Moore K and Gold MS (2011) Deleterious impact of a GABAA receptor preferring general anesthetic when used in the presence of persistent inflammation. Anesthesiology 115(4): 782-90 (PMCID:PMC3179577) Scheff, N, and Gold, MS, (2011) Sex Difference in the Inflammatory Mediator-Induced Sensitization of Dural Afferents. J Neurophysiol. 106 (4): 1662-8 (PMCID:PMC3191837) Lee KY, Charbonnet M, and Gold MS, (2012) Upregulation of high affinity GABAA receptors in cultured rat dorsal root ganglion neurons. Neuroscience 208: 133-42 (PMCID:PMC3311786) Harriott AM, Scheff N, Gold MS (In Press) The complex actions of sumatriptan on rat dural afferents (Cephalagia) D. Research Support. Research Support: Active and Completed 1R01DE018252Mechanisms of Tooth Pain PI 4/01/09 – NIH/NIDCR 02A2 2.4 mo cal. 3/31/14 (Gold) (349,658) The major goal of this project is to identify mechanisms mediating ongoing pain and sensitivity associated with inflammation of the tooth pulp. PI 4/01/09 – NIH/NINDS 2.4 mo cal. 3/31/13 NCE The major goal of this project is to identify mechanisms underlying the inflammation-induced shift in spinal GABA-A receptor circuitry. 1R01NS06301001A1 Inflammation-induced Changes in Spinal GABA-A Receptor Signaling Enhancing Post-Traumatic Pain Co-PI 7/1/10 – CDMRP Relief with Alternative Perineural 0.6 mo cal. 6/30/13 (DOD) Drugs (37,392) The major goal of this project is to identify drug combinations for use in perineural nerve blocks that will both increase the duration of nerve block as well as provide modality specificity to the nerve block. OR090012P1 Co-PI 11/1/10 – NIH 1.2 mo cal. 10/31/15 (37,900) To better define the functional consequences of Artn signaling and test the role of TRPV1 and nAChRs in GFRα3 afferent sensitization. 5R01NS033730 (Albers) Effects of artemin on nociceptors Co-PI 09/1/11 – NIH 0.6 mo cal. 08/31/16 (21,117) To develop HSV vectors that enable the expression of therapeutic targets is specific subpopulations of sensory neurons. 1R01NS06498801A2 HSV-GlyR silencing of nociceptive afferents Research Award Calcium activated chloride channels as a novel target for the treatment of migraine PI 0.6 mo cal. (50,000) 01/1/12 – 12/31/12 Migraine Research Foundation To identify the chloride channel underlying the actions of inflammatory mediators on dural afferents. Research Contract Human DRG Electrophysiology PI 2.4 mo cal. (300,000) 01/1/12 – 12/31/12 Eli Lilly To characterize the biophysical and pharmacological properties of voltage-gated Na+ currents in human dorsal root ganglion neurons. COMPLETED 03/11 CTSI P4R (PI Gold, M) Source CTSI – Virginia Kaufman Fund Title of Project Identifying the Link Between Stress and Migraine Pain The major goal of this project is to determine the impact of chronic stress on the impact of sympathetic post-ganglionic neuron activity on transmitter release, mast cell degranulation, vascular permeability and tone, and afferent activity. COMPLETED 03/11 3R01DE018252-01A2S1 (PI Gold, M) Source NIH/NIDCR Title of Project Mechanisms of Tooth Pain This is an equipment supplement to the parent grant 1R01DE018252-02A2. COMPLETED 05/09 1 RO1 NS044992-04 (PI Gold, M) Source NIH/NINDS Title of Project Inflammation-Induced Plasticity in Sensory Neurons The major goals of this project were to understand the role of CaK channels in nociceptor excitability and inflammation-induced changes in nociceptor excitability. OVERLAP: There is no scientific overlap between projects.