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
Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity.
Authors: Authors: Chiu IM, Barrett LB, Williams EK, Strochlic DE, Lee S, Weyer AD, Lou S, Bryman GS, Roberson DP, Ghasemlou N, Piccoli C, Ahat E, Wang V, Cobos EJ, Stucky CL, Ma Q, Liberles SD, Woolf CJ.
Elife
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A three-dimensional human neural cell culture model of Alzheimer's disease.
Authors: Authors: 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.
Nature
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What to call the amplification of nociceptive signals in the central nervous system that contribute to widespread pain?
Authors: Authors: Woolf CJ.
Pain
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Ronald R. Tasker Young Investigator Award 165 Promoting Endogenous GABAergic Analgesia via Kinase Modulation of Neuronal Ion Plasticity.
Authors: Authors: Kahle KT, Gao G, Zhang J, Latremoliere A, Andrews N, Shang Y, Alessi D, Woolf C, Elledge S, Clapham D.
Neurosurgery
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Diminished Schwann cell repair responses underlie age-associated impaired axonal regeneration.
Authors: Authors: 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.
Neuron
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Skin ß-endorphin mediates addiction to UV light.
Authors: Authors: Fell GL, Robinson KC, Mao J, Woolf CJ, Fisher DE.
Cell
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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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