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Researcher | Research Overview

Neuronal plasticity, its mechanistic basis, how it contributes to the normal and abnormal functions of the nervous system, and how it can be a target for therapy comprise the major focus of Dr. Woolf’s investigations. Specifically, he studies neural plasticity in relation to pain, regeneration, neurodegenerative disorders and developmental neurobiology.

Dr. Woolf has spearheaded discoveries on how functional synaptic plasticity, structural reorganization of synaptic architecture, injury-induced transcriptional changes, neuro-immune interactions and activity-dependent loss of interneurons all contribute to the pathogenesis and maintenance of pain. He has linked polymorphisms in human genes with the risk of developing pain and has pioneered new ways of phenotyping pain in patients. His work has led to the identification of novel targets for analgesics, and, with Bruce Bean at HMS, he has discovered a way of producing a long-lasting local analgesia. With Lee Rubin at HU, he has converted human embryonic stem cells into pain neurons for disease modeling and testing analgesics and with Josef Penninger used genome-wide screens in Drosophila to identify novel pain genes.

Additionally, Dr. Woolf has explored how axonal injury activates a survival and regeneration program in sensory and motor neurons, and he has identified the transcription factors that act as master regulators of these. This has led to novel genetic approaches to increase regeneration and ameliorate motor neuron disease.

Currently devoted to investigating how the functional, chemical and structural plasticity of neurons contributes to adaptive and maladaptive functions of the mammalian nervous system, the Woolf lab’s major efforts are dedicated to the study of pain, the formation of neural circuits during development, and the failure of regeneration in the adult CNS. Most of this work is focused on primary sensory and spinal cord neurons, which are studied using a multidisciplinary approach that spans mouse and human genetics, molecular and cell biology, bioinformatics, synaptic electrophysiology, neuroanatomy, integrative systems biology and behavior. The lab represents a complex mixture of basic and translational neuroscience and works closely with a wide number of academic groups and the pharmaceutical and biotechnology industry to identify and validate molecular targets for novel analgesics and axonal growth determinants. 

Some of the Group’s major current interests include: 

  • Neuro-immune interactions
  • Post-translational processing and transcriptional control of membrane receptors and ion channels mediating pain hypersensitivity
  • Intracellular signal transduction cascade in neurons
  • Role of transcription factors as master regulators of neuronal function
  • Exploiting stem cell technology to model human neurological disease
  • Mechanisms responsible for cell survival in injured sensory and motor neurons
  • Contributions of intrinsic growth determinants in establishing regenerative capacity
  • Central sensitization, its mechanism and contribution to pain
  • Bioinformatic analyses of  the transcriptome in neurons
  • Role of tetrahydrobiopterin in pain
  • Genotype – phenotype associations in pain
  • Targeting drugs selectively into neurons via large pore channels

Researcher | Research Background

Clifford Woolf, MB, BCh, PhD was appointed Director of the F.M. Kirby Neurobiology Center and the Neurobiology Program at Boston Children's Hospital in February 2010. After training for his MD and PhD at the University of the Witwatersrand in Johannesburg South Africa, Dr. Woolf moved to England in 1978. He worked at University College London for close on 20 years, towards the latter part as a Professor of Neurobiology. In 1997, Dr. Woolf moved to Boston as the first incumbent of the Richard J Kitz Chair of Anesthesia Research at Harvard Medical School and established the Neural Plasticity Research Group, based in the Department of Anesthesia and Critical Care at the Massachusetts General Hospital. Dr Woolf is a faculty member of the Harvard Stem Cell Institute and the Department of Neurobiology at Harvard Medical School.

Honors: 1973   William Cullen Medal, University of the Witwatersrand, Johannesburg, South Africa, for most distinguished B.Sc. graduate in the Faculty of Science; 1977 South African Medical Association Medal for most distinguished Medical graduate; 1987 Distinguished Young Investigator Award, International Association for the Study of Pain; 1991 Bristol-Myers Squibb Pain Research Award; 2001 Spine Society of Europe Medal; 2002 Bonica Medal; 2004 American Society of Anesthesia Award for Excellence in Research; 2009 Wall Medal, Royal College of Anaesthetists. 2010 Bonica Lecture, International Association for the Study of Pain; 2011 Javits Award NINDS; 2012  American Neurological Association F.E. Bennett Memorial Lectureship Award; 2013 Magnes Medal Israel; 2016 Reeve-Irvine Research Medal; 2017 Gill Distinguished Scientist Award; 2020 American Academy of Arts and Sciences.

Researcher | Publications