Clifford Woolf, MB, BCh, PhD
Disclosures: Founder-Nocion Therapeutics
OMB No. 0925-0046, Biographical Sketch Format Page

OMB No. 0925-0001 and 0925-0002 (Rev. 10/15 Approved Through 10/31/2018)

BIOGRAPHICAL SKETCH

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NAME: Clifford J. Woolf

eRA COMMONS USER NAME (credential, e.g., agency login): cjwoolf

POSITION TITLE: Director of FM Kirby Neurobiology Center, Boston Children’s Hospital; Professor of Neurology and Neurobiology, Harvard Medical School

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

 

University of Witwatersrand, South Africa

BSc

1972

Physiology

University of Witwatersrand, South Africa

MB, BCh

1977

Medicine

University of Witwatersrand, South Africa

PhD

1979

Physiology

Royal College of Physicians, London

MRCP

1981

Medicine

 

A. Personal Statement

 

My research is devoted to investigating how the functional, chemical and structural plasticity of neurons is involved in both the normal adaptive functions of the nervous system, and in maladaptive changes that contribute to neurological diseases, with focus on sensory and motor neurons, as well as neuro-immune interactions.

 

  1. Woolf CJ, Salter MW (2000) Neuronal plasticity - increasing the gain in pain. Science 288:1765-1768.
  2. Kehlet H, Jensen TS, Woolf CJ.  Persistent postsurgical pain: risk factors and prevention. Lancet 2006 367:1618-25. PMCID: N/A
  3. von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron. 2012 73:638-52. (PMC3319438)
  4. Talbot S, Abdulnour RE, Burkett PR, Lee S, Cronin SJ, Pascal MA, Laedermann C, Foster SL, Tran JV, Lai N, Chiu IM, Ghasemlou N, DiBiase M, Roberson D, Von Hehn C, Agac B, Haworth O, Seki H, Penninger JM, Kuchroo VK, Bean BP, Levy BD, Woolf CJ. Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation. Neuron. 2015 87:341-354 (PMC4506220)

 

I am member of the graduate Program in Neuroscience and of the Program in Immunology at Harvard Medical School and a faculty member of the Department of Neurobiology at HMS, as well as of the Harvard Stem Cell Institute, where I am co-director of the neuroscience program.

 

B.              Positions and Honors

 

Positions and Employment: 1978 Intern in Medicine and Surgery, Johannesburg General Hospital, South Africa; 1979-81 Lecturer, Middlesex Hospital Medical School, London, UK; 1981-97 Lecturer/Senior Lecturer/Professor of Neurobiology, University College London, UK; 1997-2009 Professor of Anesthesia Research, Harvard Medical School and Director Neural Plasticity Research Group Massachusetts General Hospital; 2005- Principal faculty member Harvard Stem Cell Institute (HSCI), 2010- Director of the FM Kirby Neurobiology Center and of the Program in Neurobiology, Boston Children’s Hospital, Professor of Neurology and Neurobiology, Harvard Medical School. Faculty Department of Neurobiology, Harvard Medical School. 2013- Co-director of Neuroscience Program Harvard Stem Cell Institute

 

Other Experience and Professional Memberships:  Member, Society for Neuroscience and International Association for the Study of Pain; Chairman, panel to advise the Directors of NIDCR and NINDS on the re-organization of the NIH intramural pain program 1998; Member, Arthritis Advisory Committee, FDA 2002; National Institute for Dental and Craniofacial Research, Pain and Neuroscience Working Group 2005; Chair, NIH Neuroscience Blueprint Workshop 2008; NIH Common Fund Workshop to advise Director of NIH 2012; NINDS Board of Scientific Counsellors 2015-

 

Honors: 1977 South African Medical Association, Medal for most distinguished Medical graduate; 1987 Distinguished Young Investigator Award, International Association for the Study of Pain; 1991 Bristol-Myers Squibb Pain Research Award; 2001 Spine Society of Europe Medal; 2002 Bonica Medal; 2004 American Society of Anesthesia Award for Excellence in Research; 2009 Wall Medal, Royal College of Anaesthetists; 2010 Bonica Lecture, International Association for the Study of Pain; 2011 Javits Award, NINDS. 2012 American Neurological Association, F.E. Bennett Memorial Lectureship Award; 2013 Magnes Medal, Israel; 2015 American Pain Society, Frederick W. L. Kerr Basic Science Research Award, Honorary Fellow, Faculty of Pain Medicine, College of Anesthetists, Ireland, Founder Award American Academy of Pain Medicine

 

C.              Contribution to Science

 

1. Discovery of central sensitization as a primary driver of pain hypersensitivity

 

I was the first to identify that a use-dependent synaptic plasticity in the dorsal horn of the spinal cord explained how, after injury, normally innocuous stimuli begin to evoke pain. The phenomenon of central sensitization is now recognized as a major contributor to inflammatory and neuropathic pain and I have worked to understand its mechanisms and develop new treatment strategies.

 

a)      Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature 1983;306:68683. PMCID: NA

b)      Ji RR, Baba H, Brenner JG, Woolf CJ.  Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity. Nature Neuroscience 1999. 2:1114-1119. PMCID: N/A

c)      Samad, T., Moore, K., Sapirstein, A., Billet, S., Allchorne, A., Poole, S., Bonventre, J.V. and Woolf, C.J. An interleukin-1-mediated induction of Cox-2 in the central nervous system contributes to inflammatory pain hypersensitivity Nature 2001 410:471-475. PMCID: N/A

d)  Woolf CJ. Central sensitization: Implications for the diagnosis and treatment of pain. Pain. 2011      152:S2-15 (PMC3268359).

 

2. Revealing structural and chemical plasticity in the somatosensory system after injury

 

I have devoted considerable effort to exposing the extent of the structural, chemical and functional changes that occur in adult primary sensory neurons after axonal injury or on exposure to inflammation.

 

a)      Woolf CJ, Shortland P, Coggeshall RE. Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature 1992;355:75-7. PMCID: N/A

b)      Neumann S, Doubell TP, Leslie T, Woolf CJ. Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons. Nature 1996; 384:360-364. PMCID: N/A

c)      Chiu IM, Heesters BA, Ghasemlou N, Von Hehn CA, Zhao F, Tran J, Wainger B, Strominger A, Muralidharan S, Horswill AR, Bubeck Wardenburg J, Hwang SW, Carroll MC, Woolf CJ. Bacteria activate sensory neurons that modulate pain and inflammation. Nature. 2013 501:52-7. (PMC3773968)

d)      Chiu IM, Barrett LB, Williams EK, Strochlic DE, Lee S, Weyer AD, Lou S, Bryman G, Roberson DP, Ghasemlou N, Piccoli C, Ahat E, Wang V, Cobos EJ, Stucky CL, Ma Q, Liberles SD, Woolf CJ. Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity. Elife. 2014 Dec 19;3. (PMC4383053)

 

3. Exploiting stem cell biology to study sensory and motor neurons and their diseases

 

Recently, I have begun to explore how stem cell derived or transdifferentiated neurons can be used to model neurological disease and screen for new therapeutics.

 

a)      Son EY, Ichida JK, Wainger BJ, Toma JS, Rafuse VF, Woolf CJ, Eggan K. Conversion of Mouse and Human Fibroblasts into Functional Spinal Motor Neurons. Cell Stem Cell. 2011 9:205-218. (PMC3188987)

b)      Wainger BJ, Kiskinis E, Mellin C, Wiskow O, Han SS, Sandoe J, Perez NP, Williams LA, Lee S, Boulting G, Berry JD, Brown RH Jr, Cudkowicz ME, Bean BP, Eggan K, Woolf CJ. Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons. Cell Reports 2014 Apr 10;7(1):1-11. (PMC4023477)

c)      Choi SH, Kim YH, Hebisch M, Sliwinski C, Lee S, D'Avanzo C, Chen H, Hooli B, Asselin C, Muffat J, Klee JB, Zhang C, Wainger BJ, Peitz M, Kovacs DM, Woolf CJ, Wagner SL, Tanzi RE, Kim DY. A three-dimensional human neural cell culture model of Alzheimer's disease. Nature. 2014 515:274-8. (PMC4366007)

d)      Wainger, BJ, Buttermore, ED, Oliveira, JT,Mellin, C,Lee, L, Saber, WA,Wang, AJ, Ichida, JK, Chiu, IM, Barrett, L, Huebner, EA, Bilgin,C, Tsujimoto, N, Brenneis, C, Kapur,K, Rubin, LL, Eggan, K, Woolf, CJ. Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts Nature Neuroscience 2015 18:17-24. (PMC4429606)

 

  1. Identifying new targets for the development of novel analgesics

 

I have used human gene polymorphisms, genome wide screening in Drosphila to identify new targets for analgesics and targeted delivery of small molecules in nociceptors to deliver drugs only to pain neurons.

 

a)      Neely GG, Hess A, Costigan M, Keene AC, Goulas S, Langeslag M, Griffin RS, Belfer I, Dai F, Smith SB, Diatchenko L, Gupta V, Xia CP, Amann S, Kreitz S, Heindl-Erdmann C, Wolz S, Ly CV, Arora S, Sarangi R, Dan D, Novatchkova M, Rosenzweig M, Gibson DG, Truong D, Schramek D, Zoranovic T, Cronin SJ, Angjeli B, Brune K, Dietzl G, Maixner W, Meixner A, Thomas W, Pospisilik JA, Alenius M, Kress M, Subramaniam S, Garrity PA, Bellen HJ, Woolf CJ*, Penninger JM. A genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene Cell 2010 143:628-38 *(joint senior author). (PMC3040441)

b)      Binshtok AM, Bean BP, Woolf CJ.  Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers. Nature 2007 449:607-10. PMCID: N/A

c)      Roberson DP, Gudes S, Sprague JM, Patoski HA, Robinson VK, Blasl F, Duan B, Oh SB, Bean BP, Ma Q, Binshtok AM, Woolf CJ Activity-dependent silencing reveals functionally distinct itch-generating sensory neurons Nature Neuroscience 2013 16:910-8. (PMC3695070)

d)      Latremoliere A, Latini A, Andrews N, Cronin SJ, Fujita M, Gorska K, Hovius R, Romero C, Chuaiphichai S, Painter M, Miracca G, Babaniyi O, Remor AP, Duong K, Riva P, Barrett LB, Ferreirós N, Naylor A, Penninger JM, Tegeder I, Zhong J, Blagg J, Channon KM, Johnsson K, Costigan M, Woolf CJ. Reduction of Neuropathic and Inflammatory Pain through Inhibition of the Tetrahydrobiopterin Pathway. Neuron. 2015 86:1393-406. (PMC4485422)

 

  1. Uncovering intrinsic growth as a key determinant of regenerative capacity after axonal injury

 

I have investigated the extent to which the intrinsic growth state of adult mammalian neurons contributes to their regenerative potential and the transcription factor regulators and protein effectors of this.

 

a)      Neumann S, Woolf CJ.  Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury.  Neuron 1999 23:83-91. PMCID: N/A

b)      Painter MW, Brosius Lutz A, Cheng YC, Latremoliere A, Duong K, Miller CM, Posada S, Cobos EJ, Zhang AX, Wagers AJ, Havton LA, Barres B, Omura T, Woolf CJ. Diminished schwann cell repair responses underlie age-associated impaired axonal regeneration. Neuron. 2014 Jul 16;83:331-43. (PMC4106408)

c)      Omura T, Omura K, Tedeschi A, Riva P, Painter MW, Rojas L, Martin J, Lisi V, Huebner EA, Latremoliere A, Yin Y, Barrett LB, Singh B, Lee S, Crisman T, Gao F, Li S4 Kapur K, Geschwind DH, Kosik KS, Coppola G, He Z, Carmichael ST, Benowitz LI, Costigan M, Woolf CJ Robust Axonal Regeneration Occurs in the Injured CAST/Ei Mouse CNS. Neuron. 2015 86:1215-27. (PMC4458182)

d)      Chandran V, Coppola G, Nawabi H, Omura T, Versano R, Huebner EA, Zhang A, Costigan M, Yekkirala A, Barrett L, Blesch A, Michaelevski I, Davis-Turak J, Gao F, Langfelder P, Horvath S, He Z, Benowitz L, Fainzilber M, Tuszynski M, Woolf CJ, Geschwind DH. A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program. Neuron. 2016 89:956-70 (PMC4790095).

Complete List of Published Work in My Bibliography

 

http://www.ncbi.nlm.nih.gov/sites/myncbi/1niNzd-4z9pAE/bibliography/40418115/public/?sort=date&direction=ascending

 

D.              Research Support

 

ACTIVE

 

NIH RO1DE022912 (PIs – Woolf, Scammell)                                                                                    07/26/12-06/30/17                                                                     

Sleep Disturbance as a Risk Factor for developing Chronic Pain

The goal of this project is to characterize the effect of sleep disturbance and poor sleep quality on the development of chronic pain after peripheral nerve injury.

 

NIH RO1NS038253 (PI – Woolf)                                                                                                                                            9/15/14-6/30/19                                                                     

Altered Sensibility Following Peripheral Nerve Damage                                         

The goal of this project is to exploit human stem cells to study pain in a dish.

 

NIH-NINDS R37NS039518 (PI – Woolf)                                                                                                                7/01/11 - 6/30/18                           

Neural Plasticity and Inflammatory Pain

The aim is to understand the mechanisms that contribute to the development of inflammatory pain.

 

NIH PO1NS072040-01A1 (PD/PI – Clapham, D)                                                                      08/01/11-07/31/16             

TRP Channel Mediated Pain Circuitry                                                                                                                Woolf Role: PI, Core Director

The goal of this project is to study the role of TRP channels in the production of pain and itch. 

 

NIH/NICHD P30 HD018655 (PD – Pomeroy, S)                                                                                    9/29/11-6/30/16             

Intellectual and Developmental Disabilities Research Center                             Woolf role: Associate Director 

Provide state-of the core facilities to all projects within the IDDRC program.

 

Pfizer (PD/PI: Woolf)                                                                                                                                                                                      1/1/16-              6/1/17                                                                                   

Complex spontaneous single cell calcium flux analysis for high-throughput screening

The goal of this project is to conduct an excitability phenotypic drug screen on motor neurons.

 

ALS Therapy Alliance (PD/PI: Woolf)                                                          10/15/15-0/15/17                                                  

Hyperexcitabiliy in ALS: Identification of transcriptional drivers and responders.

The goal of this project is to identify causes and effects of human MN hyperexcitability in ALS.

 

COMPLETED

 

Massachusetts Life Sciences Consortium (PI: Woolf)                                                        6/1/13-2/1/15                                                                                   

Molecular Genetic Validation in Mice of Candidate Human               Neuropathic Pain Targets

The goals of this project is to enable a reverse engineering platform from human gene target identification to mouse mechanistic studies for testing new neuropathic pain treatments.

 

Columbia University Medical Center (PD/PI: Woolf)                                                                      5/1/13-4/30/16             

Target ALS Research Network                                                                                                                             

Spinal and Corticospinal Motor Neuron Excitability and ALS                                                       

The goal of this project is to determine what molecular mechanisms contribute to hyper-excitability in motor neurons derived from different ALS patients. 

 

GSK (PD/PI: Woolf)                                                                                                                                                4/30/15-4/29/16                      

Discovering new ion channel modulator drugs for ALS                                

The goal of this project is to scale the production of the iPS-derived motor neurons for the screening of novel Retigabine analogs and other ion channel modulators in motor neuron diseases.