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
Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity.
Authors: Authors: Sorge RE, Trang T, Dorfman R, Smith SB, Beggs S, Ritchie J, Austin JS, Zaykin DV, Vander Meulen H, Costigan M, Herbert TA, Yarkoni-Abitbul M, Tichauer D, Livneh J, Gershon E, Zheng M, Tan K, John SL, Slade GD, Jordan J, Woolf CJ, Peltz G, Maixner W, Diatchenko L, Seltzer Z, Salter MW, Mogil JS.
Nat Med
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Deconstructing the neuropathic pain phenotype to reveal neural mechanisms.
Authors: Authors: von Hehn CA, Baron R, Woolf CJ.
Neuron
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Analgesia by inhibiting tetrahydrobiopterin synthesis.
Authors: Authors: Costigan M, Latremoliere A, Woolf CJ.
Curr Opin Pharmacol
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Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception.
Authors: Authors: Neely GG, Rao S, Costigan M, Mair N, Racz I, Milinkeviciute G, Meixner A, Nayanala S, Griffin RS, Belfer I, Dai F, Smith S, Diatchenko L, Marengo S, Haubner BJ, Novatchkova M, Gibson D, Maixner W, Pospisilik JA, Hirsch E, Whishaw IQ, Zimmer A, Gupta V, Sasaki J, Kanaho Y, Sasaki T, Kress M, Woolf CJ, Penninger JM.
PLoS Genet
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The BMP coreceptor RGMb promotes while the endogenous BMP antagonist noggin reduces neurite outgrowth and peripheral nerve regeneration by modulating BMP signaling.
Authors: Authors: Ma CH, Brenner GJ, Omura T, Samad OA, Costigan M, Inquimbert P, Niederkofler V, Salie R, Sun CC, Lin HY, Arber S, Coppola G, Woolf CJ, Samad TA.
J Neurosci
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Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice.
Authors: Authors: Ma CH, Omura T, Cobos EJ, Latrémolière A, Ghasemlou N, Brenner GJ, van Veen E, Barrett L, Sawada T, Gao F, Coppola G, Gertler F, Costigan M, Geschwind D, Woolf CJ.
J Clin Invest
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Soluble epoxide hydrolase limits mechanical hyperalgesia during inflammation.
Authors: Authors: Brenneis C, Sisignano M, Coste O, Altenrath K, Fischer MJ, Angioni C, Fleming I, Brandes RP, Reeh PW, Woolf CJ, Geisslinger G, Scholich K.
Mol Pain
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Conversion of mouse and human fibroblasts into functional spinal motor neurons.
Authors: Authors: Son EY, Ichida JK, Wainger BJ, Toma JS, Rafuse VF, Woolf CJ, Eggan K.
Cell Stem Cell
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Targeting of sodium channel blockers into nociceptors to produce long-duration analgesia: a systematic study and review.
Authors: Authors: Roberson DP, Binshtok AM, Blasl F, Bean BP, Woolf CJ.
Br J Pharmacol
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Considerations for extrapolating evidence of acute and chronic pain analgesic efficacy.
Authors: Authors: Dworkin RH, Turk DC, Basch E, Berger A, Cleeland C, Farrar JT, Haythornthwaite JA, Jensen MP, Kerns RD, Markman J, Porter L, Raja SN, Ross E, Todd K, Wallace M, Woolf CJ.
Pain
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