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Sensory Cells and Circuits Lab

About

Lab Chief: Alexander Chesler, Ph.D.

Alexander (Alex) Chesler, Ph.D., heads the Sensory Cells and Circuits Lab. This lab is interested in how sensory input is detected and processed by the brain to evoke specific behaviors. Our work focuses on identifying peripheral somatosensory neurons tuned to specific types of stimuli, the molecules they use for transduction, and the neural circuits that they activate. Through our research we seek to understand the basis by which some stimuli are perceived as innocuous while others are perceived as noxious and how these distinctions are modulated by physiological state or prior experience. The hope is that improving our knowledge of these basic mechanisms will be useful in developing new therapeutic approaches for treating acute and chronic pain. Our lab uses mouse genetics, in vitro and in vivo electrophysiology, in vivo two-photon imaging, and behavior to study how sensory stimuli are detected and encoded. Together, these approaches help us to better understand the importance of specific molecules for the responses of defined classes of sensory neurons and to map neural pathways for touch and pain in the brain. In parallel, we have identified a cohort of patients with a rare inherited disorder affecting mechanosensation due to damaging mutations in the gene PIEZO2. Studying these patients helped define the role of this particular gene in human mechanosensation and allowed us to probe basic questions about the role select sensory inputs play in perception. Most importantly, working with these patients allows us to ask questions about human experience that, by definition, are impossible to answer using animal models. We are now positioned to take what we learn from these patients to guide our studies in mice and vice versa.

Lab Chief

Chesler_Headshot

Dr. Chesler received his degrees from Bard College (B.A., 1995) and Columbia University (Ph.D., 2005). His graduate study, in the laboratory of Dr. Stuart Firestein, was focused on the function and development of olfactory sensory neurons. He did his postdoctoral training in the laboratory of Dr. David Julius at the University of California, San Francisco, where he combined physiological, anatomical, and behavioral approaches to study the pharmacology of somatosensory neurons. He was recruited to the National Institutes of Health (NIH) intramural pain program in 2013 as a Stadtman Investigator and became a senior investigator in 2020 with joint appointments in the National Center for Complementary and Integrative Health and the National Institute of Neurological Disorders and Stroke. His laboratory employs multidisciplinary approaches to study how sensory stimuli, such as temperature, touch, and environmental irritants, are detected and encoded by the somatosensory system in mice and humans. His research seeks to uncover the basis by which some stimuli are perceived as innocuous while others are perceived as noxious and how these distinctions are modulated by physiological state or prior experience. The hope is that improving our knowledge of these basic mechanisms will be useful in developing new therapeutic approaches for treating acute and chronic pain.  Among his achievements within the intramural program, Dr. Chesler has received two DDIR (Deputy Director of Intramural Research) Innovation Awards for his work on pain, a Bench-to-Bedside award focused on the use of natural products to treat mechanical allodynia, a Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®-funded collaboration with NCATs to discover new treatments for chronic pain, and has helped to establish the NIH Pain Research Center in the NIH Clinical Center.