PiN Faculty Member - William Renthal, MD, PhD

William Renthal, MD, PhD

Assistant Professor

Brigham and Women's Hospital
Hale BTM 7002K
60 Fenwood Rd.
Boston, MA 02115
Tel: 617.278.0540
Email: wrenthal@bwh.harvard.edu
Visit my lab page here.



Chronic pain and headache disorders are two leading causes of disability world-wide. Improving treatments for these conditions is a major focus of my lab as well as my clinical practice as a neurologist. The experience of pain begins with specialized peripheral sensory neurons (nociceptors) whose cell bodies reside in dorsal root ganglia at each spinal level or in the trigeminal ganglia at the skull base. Persistent hyperexcitability of nociceptors is thought to underlie many types of chronic pain, but major gaps remain in our understanding of this process. Our group studies the molecular mechanisms underlying nociceptor sensitization with a special interest in headache disorders. Our long-term goal is to identify molecular features that are unique to nociceptors and to leverage this knowledge to develop novel, nociceptor-specific pain therapeutics. Toward this goal, we built single-cell gene expression atlases of both mouse pain models and human nociceptors and are using this information to control nociceptor activity through both genetic loss of function studies in mice and the development of nociceptor-specific viral vectors.

We are also interested in the epigenomic principles underlying neuronal plasticity, a process which enables neurons to adapt to environmental stimuli. An extreme example of this plasticity occurs after axonal injury of peripheral sensory neurons. Using single-cell genomics, we found that axonal injury induces a transcriptional response in sensory neurons that both promotes axonal regeneration and suppresses cell identity. This transcriptional reprogramming resolves over a similar time course as target reinnervation and is followed by the restoration of original cell identity. Our group is working to understand the transcription factors and epigenomic mechanisms that drive injury-induced transcriptional reprogramming, interesting parallels to stem cell fate reprogramming, and how these general principles provide sensory neurons with a unique ability to survive injury. Better understanding of these mechanisms could guide new approaches to repairing central nervous system neurons in neurogenerative disorders or after trauma or stroke.

To address these questions, our group uses molecular tools such as single-cell genomics, gene editing, advanced imaging, mouse models, and post-mortem human tissue. We work closely with headache and pain neurology and pathology at the Brigham and Women’s Hospital and Massachusetts General Hospital to accelerate clinical translation of our research.



Last Update: 9/16/2020



Publications

For a complete listing of publications click here.

 


 



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