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
Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1.
Authors: Authors: Kiskinis E, Sandoe J, Williams LA, Boulting GL, Moccia R, Wainger BJ, Han S, Peng T, Thams S, Mikkilineni S, Mellin C, Merkle FT, Davis-Dusenbery BN, Ziller M, Oakley D, Ichida J, Di Costanzo S, Atwater N, Maeder ML, Goodwin MJ, Nemesh J, Handsaker RE, Paull D, Noggle S, McCarroll SA, Joung JK, Woolf CJ, Brown RH, Eggan K.
Cell Stem Cell
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Therapeutic restoration of spinal inhibition via druggable enhancement of potassium-chloride cotransporter KCC2-mediated chloride extrusion in peripheral neuropathic pain.
Authors: Authors: Kahle KT, Khanna A, Clapham DE, Woolf CJ.
JAMA Neurol
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Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons.
Authors: Authors: Wainger BJ, Kiskinis E, Mellin C, Wiskow O, Han SS, Sandoe J, Perez NP, Williams LA, Lee S, Boulting G, Berry JD, Brown RH, Cudkowicz ME, Bean BP, Eggan K, Woolf CJ.
Cell Rep
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Casting light on pain.
Authors: Authors: Browne LE, Woolf CJ.
Nat Biotechnol
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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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