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
ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation.
Authors: Authors: Seijffers R, Zhang J, Matthews JC, Chen A, Tamrazian E, Babaniyi O, Selig M, Hynynen M, Woolf CJ, Brown RH.
Proc Natl Acad Sci U S A
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Bupivacaine-induced cellular entry of QX-314 and its contribution to differential nerve block.
Authors: Authors: Brenneis C, Kistner K, Puopolo M, Jo S, Roberson D, Sisignano M, Segal D, Cobos EJ, Wainger BJ, Labocha S, Ferreirós N, von Hehn C, Tran J, Geisslinger G, Reeh PW, Bean BP, Woolf CJ.
Br J Pharmacol
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Bacteria activate sensory neurons that modulate pain and inflammation.
Authors: Authors: 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.
Nature
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Activity-dependent silencing reveals functionally distinct itch-generating sensory neurons.
Authors: Authors: Roberson DP, Gudes S, Sprague JM, Patoski HA, Robson VK, Blasl F, Duan B, Oh SB, Bean BP, Ma Q, Binshtok AM, Woolf CJ.
Nat Neurosci
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A small molecule screen in stem-cell-derived motor neurons identifies a kinase inhibitor as a candidate therapeutic for ALS.
Authors: Authors: Yang YM, Gupta SK, Kim KJ, Powers BE, Cerqueira A, Wainger BJ, Ngo HD, Rosowski KA, Schein PA, Ackeifi CA, Arvanites AC, Davidow LS, Woolf CJ, Rubin LL.
Cell Stem Cell
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Photochemical activation of TRPA1 channels in neurons and animals.
Authors: Authors: Kokel D, Cheung CY, Mills R, Coutinho-Budd J, Huang L, Setola V, Sprague J, Jin S, Jin YN, Huang XP, Bruni G, Woolf CJ, Roth BL, Hamblin MR, Zylka MJ, Milan DJ, Peterson RT.
Nat Chem Biol
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Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314.
Authors: Authors: Puopolo M, Binshtok AM, Yao GL, Oh SB, Woolf CJ, Bean BP.
J Neurophysiol
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CLP1 links tRNA metabolism to progressive motor-neuron loss.
Authors: Authors: Hanada T, Weitzer S, Mair B, Bernreuther C, Wainger BJ, Ichida J, Hanada R, Orthofer M, Cronin SJ, Komnenovic V, Minis A, Sato F, Mimata H, Yoshimura A, Tamir I, Rainer J, Kofler R, Yaron A, Eggan KC, Woolf CJ, Glatzel M, Herbst R, Martinez J, Penninger JM.
Nature
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Personalized medicine and opioid analgesic prescribing for chronic pain: opportunities and challenges.
Authors: Authors: Bruehl S, Apkarian AV, Ballantyne JC, Berger A, Borsook D, Chen WG, Farrar JT, Haythornthwaite JA, Horn SD, Iadarola MJ, Inturrisi CE, Lao L, Mackey S, Mao J, Sawczuk A, Uhl GR, Witter J, Woolf CJ, Zubieta JK, Lin Y.
J Pain
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Phenotyping the function of TRPV1-expressing sensory neurons by targeted axonal silencing.
Authors: Authors: Brenneis C, Kistner K, Puopolo M, Segal D, Roberson D, Sisignano M, Labocha S, Ferreirós N, Strominger A, Cobos EJ, Ghasemlou N, Geisslinger G, Reeh PW, Bean BP, Woolf CJ.
J Neurosci
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