Clifford Woolf

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