Clifford Woolf

Clifford Woolf, MB, BCh, PhD

Professor of Neurology, Harvard Medical School

Adaptive and Maladaptive Plasticity in Sensory and Motor Systems

Neurons are subject to functional, chemical and structural plasticity. This plasticity is an important factor both in the normal function of the nervous system and in a vast range of neurological diseases.

The Woolf lab studies how different forms of neuronal plasticity contribute both to adaptive and maladaptive changes in the mammalian nervous system, particularly in relation to pain, regeneration and neurodegenerative diseases.

Most of our work is concentrated on primary sensory and motor neurons, and to the interaction of neurons and immune cells, using a multidisciplinary approach spanning stem cell, molecular and cell biology, electrophysiology, neuroanatomy, behavior and genetics. We have established functional and comparative genomic strategies using expression profiling, bioinformatics and gain- and loss-of-function approaches, to screen for novel genes that contribute to neuronal plasticity and disease phenotypes. Our group works closely with many academic groups and the pharmaceutical industry to model disease and identify molecular targets for novel analgesics, axonal growth determinants and neuroprotective agents.

Current research includes study of the transcriptional control and post-translational processing of receptors and ion channels that mediate pain hypersensitivity, selective silencing of defined neuronal populations, intracellular signal transduction cascades activated by peripheral inflammation and nerve injury, neuro-immune interactions, transcription factors as master regulators of pain, growth and survival programs, cell survival in injured sensory and motor neurons, and the contribution of intrinsic growth determinants in establishing regenerative capacity in the peripheral and central nervous system. We are an active part of the Harvard Stem Cell Institute and are investigating how sensory and motor neurons reprogrammed from patient fibroblasts can be used to study pain and motor neuron disease and to screen for new treatments.

Publications View
BACE1 regulates voltage-gated sodium channels and neuronal activity.
Authors: Authors: Kim DY, Carey BW, Wang H, Ingano LA, Binshtok AM, Wertz MH, Pettingell WH, He P, Lee VM, Woolf CJ, Kovacs DM.
Nat Cell Biol
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Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors.
Authors: Authors: Agarwal N, Pacher P, Tegeder I, Amaya F, Constantin CE, Brenner GJ, Rubino T, Michalski CW, Marsicano G, Monory K, Mackie K, Marian C, Batkai S, Parolaro D, Fischer MJ, Reeh P, Kunos G, Kress M, Lutz B, Woolf CJ, Kuner R.
Nat Neurosci
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Reliable screening for a pain-protective haplotype in the GTP cyclohydrolase 1 gene (GCH1) through the use of 3 or fewer single nucleotide polymorphisms.
Authors: Authors: Lötsch J, Belfer I, Kirchhof A, Mishra BK, Max MB, Doehring A, Costigan M, Woolf CJ, Geisslinger G, Tegeder I.
Clin Chem
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Central sensitization: uncovering the relation between pain and plasticity.
Authors: Authors: Woolf CJ.
Anesthesiology
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The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity.
Authors: Authors: Amaya F, Wang H, Costigan M, Allchorne AJ, Hatcher JP, Egerton J, Stean T, Morisset V, Grose D, Gunthorpe MJ, Chessell IP, Tate S, Green PJ, Woolf CJ.
J Neurosci
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Prostaglandin E2 receptor EP4 contributes to inflammatory pain hypersensitivity.
Authors: Authors: Lin CR, Amaya F, Barrett L, Wang H, Takada J, Samad TA, Woolf CJ.
J Pharmacol Exp Ther
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GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence.
Authors: Authors: Tegeder I, Costigan M, Griffin RS, Abele A, Belfer I, Schmidt H, Ehnert C, Nejim J, Marian C, Scholz J, Wu T, Allchorne A, Diatchenko L, Binshtok AM, Goldman D, Adolph J, Sama S, Atlas SJ, Carlezon WA, Parsegian A, Lötsch J, Fillingim RB, Maixner W, Geisslinger G, Max MB, Woolf CJ.
Nat Med
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Constitutive cyclo-oxygenase-2 does not contribute to the development of human visceral pain hypersensitivity.
Authors: Authors: Willert RP, Delaney C, Hobson AR, Thompson DG, Woolf CJ, Aziz Q.
Eur J Pain
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Perceptual wind-up in the human oesophagus is enhanced by central sensitisation.
Authors: Authors: Sarkar S, Woolf CJ, Hobson AR, Thompson DG, Aziz Q.
Gut
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Persistent postsurgical pain: risk factors and prevention.
Authors: Authors: Kehlet H, Jensen TS, Woolf CJ.
Lancet
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