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OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015)
BIOGRAPHICAL SKETCH
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NAME: Sulayman D. Dib-Hajj
eRA COMMONS USER NAME (credential, e.g., agency login): sdib-hajj
POSITION TITLE: Senior Research Scientist, Yale School of Medicine; Research Biologist, VA
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing,
include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION
DEGREE
(if
applicable)
Completion
Date
MM/YYYY
FIELD OF STUDY
The American University of Beirut, Lebanon
B.S.
1977
Biology
The Ohio State University, Columbus, OH
Ph.D.
1990
Mol. Cell. Dev. Biol.
A. Personal Statement
As the PI or co-Investigator on several previous VA- and industry-funded grants, I have gained a broad
background in the pathophysiological basis of excitability disorders including neuropathic pain, multiple
sclerosis and epilepsy. My research for the past 20 years has involved the identification and characterization of
mutations in voltage-gated sodium channels Nav1.7, Nav1.8 and Nav1.9 in patients with heritable pain
disorders and the assessment of the contribution of individual sodium channel isoforms to firing properties of
neurons. By virtue of the tissue-specific expression of these sodium channels Nav1.7, Nav1.8 and Nav1.9
have become main targets for development of novel and non-addictive pain therapeutics with potentially
minimal cognitive and cardiac side effects. Nav1.6 is the main sodium channel at nodes of Ranvier in CNS
and PNS, and has been shown to contribute to conduction in small fiber sensory neurons. In addition to our
studies showing that mutations in Nav1.6 underlie infantile epileptic encephalopathies, we have now shown
that a gain-of-function variant in Nav1.6 is a risk factor for trigeminal neuralgia. We also have ongoing animal
studies using tissue-specific Nav1.6 knockout mice to elucidate the role of this channel in a variety of animal
pain models. Another aspect of my research focuses on the identification and characterization of sodium
channel partners that modulate channel function, protein stability, and polarized distribution of different channel
isoforms to neuronal compartments.
B. Positions and Honors
Positions and Employment:
1990-92
1992-94
1995-00
2000-12
2011-
Post-doctoral fellow, Department of Entomology, Center for Advanced Invertebrate Molecular
Sciences (cAIMS), Institute of Biosciences and Technology, Texas A&M Univ., College Station,
Texas
Assistant Research Scientist, Department of Entomology, Center for Advanced Invertebrate
Molecular Sciences (cAIMS), Institute of Biosciences and Technology, Texas A&M Univ, College
Station, Texas
Associate Research Scientist, Department of Neurology & The Center for Neuroscience and
Regeneration Research, Yale University School of Medicine, New Haven, CT.
Research Scientist, Department of Neurology & The Center for Neuroscience and Regeneration
Research, Yale University School of Medicine, New Haven, CT, and, Rehabilitation Research
Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT
Research Biologist, Center for Restoration of Nervous System Function, Veterans Affairs
Connecticut Healthcare System, West Haven, CT
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2012-
Senior Research Scientist, Department of Neurology & The Center for Neuroscience and
Regeneration Research, Yale University School of Medicine and Graduate School, New Haven,
CT, and, Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West
Haven, CT.
Associate Director, Center for Restoration of Nervous System Function, Veterans Affairs
Connecticut Healthcare System, West Haven, CT
2012Other Experience and Professional Memberships:
Grant Reviews
2008
2010
2011
2012
2012-
Ad hoc member of the Somatosensory and Chemosensory Systems Study Section, NIH, USA; Ad
hoc reviewer for the Welcome Trust, UK.
Ad hoc reviewer of the Summer 2010 Merit review for Rehabilitation Research & Development,
Department of Veterans Affairs, USA.
Ad hoc reviewer of the Fall 2010 Merit review for Medical Research Service (Neuro C), Department
of Veterans Affairs, USA
Ad hoc reviewer of the Spring and Fall 2011 Merit review for Medical Research Service,
Department of Veterans Affairs, USA
Ad hoc reviewer for the American Institute of Biological Sciences (AIBS) on behalf of the US Army
Medical Research and Materiel Command (USAMRMC).
Ad hoc reviewer for Association Francaise Contre Les Myopathies (AFM);
Ad hoc reviewer of the Somatosensory and Chemosensory Systems Study Section, NIH, USA
Ad hoc reviewer for the Killam Felloship, Canada Council for the Arts.
Ad hoc reviewer for the European Research Projects on Rare Diseases (e-rare-2-europe).
Permanent member of the Merit review panel for Medical Research Service (Neuro B), Department
of Veterans Affairs, USA
Editorial Boards:
2008- present
2009- present
2010
2010- 2016
2012- present
Associate Editor: The Open Pain Journal, and The Open Drug Discovery Journal
Associate Editor: Pain Research and Treatment
Guest Editor, Neuroscience Letters special issue: Proteomics of ion channels.
Associate Editor (Cellular/Molecular section): The Journal of Neuroscience
Review Editorial Board: Frontiers in Pharmacology of Ion Channels and Channelopathies
Editorial Board of Physiology Journal
Editorial Board of Molecular Pain
Ad hoc journal reviewer
Science, Annals of Neurology, Brain, Nature Protocols, Journal of Biological Chemistry, Journal of Physiology,
Pain, Lancet Neurology, European Journal of Pain, Journal of Neurophysiology, Journal of
Neuropharmacology, British Journal of Pharmacology
C. Contribution to Science 174 primary and review papers and 7 book chapters (h index: 54)
1. My early work defined the effect of nerve injury on expression of peripheral sodium channels, and
rescue with trophic factors.
a. Dib-Hajj, S. D., Black, J. A, Felts, P. A. and Waxman, S. G. (1996). Down-regulation of transcripts for
Na channel subunit -SNS in spinal sensory neurons following axotomy. Proc. Natl. Acad. Sci., USA.
93, 14950-14954.
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b. Dib-Hajj, S. D., Ishikawa, K., Cummins, T. R., Waxman, S. G. (1997). Insertion of SNS-specific
tetrapeptide in S3-S4 linker of domain 4 accelerates recovery from inactivation of skeletal muscle
voltage-gated Na channel 1 in HEK293 cells. FEBS Letters, 416, 11-14.
c. Dib-Hajj, S. D, Black, J. A., Cummins, T. R., Kenney, A., Kocsis, J., Waxman, S. G. (1998). Rescue of
sodium channel -SNS expression in small dorsal root ganglia neurons following axotomy by in vivo
administration of nerve growth factor. J. Neurophysiol, 79: 2668-2676.
d. Dib-Hajj, S. D., Fjell, J., Cummins, T. R., Zheng, Z., Fried, K., LaMotte, R., Black, J. A., Waxman, S. G.
(1999). Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury
model of neuropathic pain. Pain 83, 591-600.
e. Cummins, TR, Black, JA, Dib-Hajj, SD, Waxman, SG (2000). GDNF upregulates expression of
functional SNS and NaN sodium channels and their currents in axotomized DRG neurons. J. Neurosci.
20, 8754-8761.
2. I extended these studies to the identification and cloning of a novel sensory neuron specific
sodium channel Nav1.9 from rodent and humans and modulation of peripheral sodium channels
a. Dib-Hajj, S. D., Tyrrell, L., Black, J. A., Waxman, S. G. (1998). NaN, a novel voltage-gated Na channel
preferentially expressed in peripheral sensory neurons and down-regulated following axotomy. Proc.
Natl. Acad. Sci., USA. 95, 8963-8968
b. Cummins, T. R., Dib-Hajj, S. D., Black, J. A., Akopian, A. N., Wood, J. N., Waxman, S. G. (1999). A
novel persistent tetrodotoxin-resistant sodium current in sns-null and wild type small primary sensory
neurons. J. Neurosci, 19, RC43 (1-6).
c. Wittmack, E, K., Rush, A. M., Craner, M. J., Goldfarb, M, Waxman, S. G., Dib-Hajj, S. D. (2004).
Fibroblast Growth Factor Homologous Factor 2B: association with Nav1.6 and selective co-localization
at nodes of Ranvier of dorsal root axons. J Neurosci. 24:6765-6775. PMID:15282281.
d. Hudmon, A, Choi, JS, Tyrrell, L, Black, JA, Rush, AM, Waxman, SG and Dib-Hajj, SD (2008)
Phosphorylation of sodium channel Nav1.8 by p38 mitogen-activated protein kinase increases current
density in dorsal root ganglion neurons. J Neurosci, 28 (12): 3190-3201.
e. Stamboulian, S, Choi, J-S, Ahn, H-S, Chang, Y-W, Tyrell, L, Black, JA, Waxman, SG, Dib-Hajj, SD
(2010) ERK1/2 phosphorylates sodium channel Nav1.7 and alters its gating properties. J Neurosci,
30(5):1637-1647.
3. Following up on studies delineating the role of peripheral sodium channels in neuropathic and
inflammatory pain in animal models, I carried out molecule-to-man studies to demonstrate the
contribution of mutations in human sodium channels to human pain.
a. Dib-Hajj, SD, Rush, AM, Cummins, TR, Hisama, FM, Novella, S, Tyrrell, L, Marshall, L, Waxman, SG
(2005) Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory
neurons. Brain, 128:1847-1854.
b. Rush AM, Dib-Hajj SD, liu, S, Cummins, T.R. Black, J. A. Waxman SG. (2006). A single sodium
channel mutation produces hyper- or hypoexcitability in different types of neurons. PNAS (USA), 103:
8245-8250.
c. Faber, C.G., Hoeijmakers, J.G.J., Ahn, H.S., Cheng, X, Han, C., Choi, J.S., Estacion, M., Lauria, G.,
Vanhoutte, E.K., Gerrits, M.M., Dib-Hajj, S., Drenth, J.P.H., Waxman, S.G., and Merkies, I.S.J. Gainof-function NaV1.7 mutations in idiopathic small fiber neuropathy. Annals of Neurology, 71(1):26-39,
2012.
d. Dib-Hajj, S.D., Yang, Y., Black, J.A., Waxman, S.G. The NaV1.7 sodium channel: from molecule to
man. Nature Rev Neurosci, 14(1): 49-62, 2013 (Comprehensive review on role of Nav1.7 in human
pain disorders).
e. Huang, J., Han, C., Estacion, M., Vasylyev, D., Hoeijmakers, J.G.J., Gerrits, M.M., Tyrrell, L., Lauria,
G., Faber, C.G., Dib-Hajj, S.D., Merkies, I.S.J., Waxman, S.G. Gain-of-function mutations in sodium
channel NaV1.9 in painful neuropathy. Brain, 137(Pt.6): 1627-1642, 2014.
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4. In recent ongoing work, I have collaborated with other members of the group to use atomic-level
structural modeling to advance a novel pharmacogenomics approach to pain treatment.
a. Yang, Y., Dib-Hajj, S.D., Zhang, J., Zhang, Y., Tyrrell, L., Estacion, M., and Waxman, S.G. Structural
modeling and mutant cycle analysis predict pharmacoresponsiveness of a NaV1.7 mutant channel,
Nature Comm., 3: 1186, 2012.
b. McDonnell A, Schulman B, Ali Z, Dib-Hajj SD, Brock F, Cobain S, Mainka T, Vollert J, Tarabar S,
Waxman SG (2016) Inherited Erythromelalgia due to mutations in SCN9A: natural history, clinical
phenotype and somatosensory profile. Brain, 139(Pt 4):1052-65. doi: 10.1093/brain/aww007. PMID:
26920677
c. Alexandrou AJ, Brown AR, Chapman ML, Estacion M, Turner J, Mis MA, Wilbrey A, Payne EC,
Gutteridge A, Cox PJ, Doyle R, Printzenhoff D, Lin Z, Marron BE, West C, Swain NA, Storer RI,
Stupple PA, Castle NA, Hounshel JA, Rivarac M, Randall A, Dib-Hajj SD, Krafte D, Waxman SG, Patel
MK, Butt RP, Stevens EB (2016) Subtype-selective small molecule inhibitors reveal a fundamental role
for Nav1.7 in nociceptor electrogenesis, axonal conduction and presynaptic release. PLoS One,
11(4):e0152405. doi: 10.1371/journal.pone.0152405. PMID: 27050761.
d. Geha P, Yang Y, Estacion M, Sculman BR, Tokuno H, Apkarian AV, Dib-Hajj SD, Waxman SG (2016)
Pharmacotherapy for pain in a family with inherited erythromelalgia guided by genomic analysis and
functional profiling. JAMA Neurol, 73(6):659-67. doi: 10.1001/jamaneurol.2016.0389. PMID: 27088781.
5. In a different line of investigation, I have worked on identification of molecular determinants that
are important for sodium channel stability at the plasma membrane and targeted trafficking to
different neuronal compartments.
a. Wittmack, E, K., Rush, A. M., Craner, M. J., Goldfarb, M, Waxman, S. G., Dib-Hajj, S. D. (2004).
Fibroblast Growth Factor Homologous Factor 2B: association with Nav1.6 and selective co-localization
at nodes of Ranvier of dorsal root axons. J Neurosci. 24:6765-6775. PMID:15282281.
b. Gasser, A, Cheng, X, Gilmore, ES, Tyrrell, L, Waxman, SG and Dib-Hajj, SD (2010) Two Nedd4binding motifs underlie modulation of sodium channel Nav1.6 by p38 MAPK. J Biol Chem.
285(34):26149-61. PMID:20530479.
c. Gasser, A, Ho, TS-Y, Cheng, X, Chang, K-J, Waxman, SG, Rasband, MN and Dib-Hajj, SD (2012) An
ankyrinG-binding motif is necessary and sufficient for targeting NaV1.6 sodium channels to axon initial
segments and nodes of Ranvier. J Neurosci, 32(21):7232-7243. PMID:22623668.
d. Akin EJ, Solé L, Dib-Hajj SD, Waxman SG and Tamkun MM (2015) Preferential targeting of Nav1.6
voltage-gated Na+ channels to the initial segment during axon initial segment development. PLoS One
10(4):e0124397. PMID: 25874799
Complete List of Published Work in My Bibliography: http://www.ncbi.nlm.nih.gov/pubmed/?term=Dib-Hajj+S
D. Research Support
Ongoing Research Support
Project title: Rehabilitation R&D Center for Restoration of Function in MS and SCI
Agency: Department of Veterans Affairs; Type: Center Grant # B9253-C
Role: Co-PI (PI: Stephen G. Waxman, MD, PhD)
Project Timeframe: 10/1/14 – 9/30/19
Project title: Neuromolecular Basis for Pain in SCI and Burn Injury
Agency: Department of Veterans Affairs; Type: Merit Review;
Role: Co-PI (PI Stephen G. Waxman, MD, PhD)
Project Timeframe: 10/1/14 – 9/30/18
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Completed Research Support
Project title: Role of sodium channel Nav1.6 in neuropathic pain
Agency: Department of Veterans Affairs; Type: Merit Review;
Role: PI
Project Timeframe: 10/1/12 – 9/30/16
Project title: Effect of small molecule blocker on neuronal excitability
Agency: Pfizer Pharmaceuticals, Inc. Type: Grant
Role: Co-PI (PI Stephen G. Waxman, MD PhD)
Project Timeframe: 3/1/11 – 2/29/12
Project title: Effect of ranolazine on neuronal excitability
Agency: Gilead Biosciences, Inc. Type: Grant
Role: PI
Project Timeframe: 7/28/2008 – 5/31/2010
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