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Stadtman Investigator

Alexander Chesler, Ph.D.

Sensory Cells and Circuits Section

Porter Neuroscience Research Center
Building 35 Room 1D822
Convent Drive 35A
Bethesda MD 20892
Office: (301) 594-1049


alexander.chesler@nih.gov

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 NIH intramural pain program in 2013 as a Stadtman Investigator and became a Senior Investigator in 2020 with joint appointments in NCCIH and NINDS. His laboratory employs multidisciplinary approaches to study how sensory stimuli, such 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 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, he has received two DDIR Innovation Awards for his work on pain, a Bench-to-Bedside award focused on the use of natural products to treat mechanical allodynia, a HEAL-initiative funded collaboration with NCATs to discover new treatments for chronic pain and has helped establish the NIH Pain Research Center in the Clinical Center.



The central question guiding research in the Chesler Lab is 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 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 mechanosenstion 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 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.

Staff Image
  • NIma Ghitani, Ph.D
    Staff Scientist

  • Ruby Lam, B.S.
    Graduate Student
    Brown-NIH GPP program

  • Domnhall MacDonald, Ph.D
    Postdoctoral Fellow

  • Max Nagel, Ph.D
    Postdoctoral Fellow

  • Alec Nickolls, Ph.D
    Postdoctoral Fellow

  • Jennifer Osborne, B.S.
    Postdoctoral Fellow

  • Sarah Shynader, B.S.
    Postdoctoral Fellow

  • 1) Chesler AT*, Szczot M, Bharucha-Goebel D, Čeko M, Donkervoort S, Laubacher C, Hayes LH, Alter K, Zampieri C, Stanley C, Innes AM, Mah JK, Grosmann CM, Bradley N, Nguyen D, Foley AR, Le Pichon CE, Bönnemann CG*.
  • The Role of PIEZO2 in Human Mechanosensation. New England Journal of Medicine. 2016 Oct 6;375(14):1355-1364. Epub 2016 Sep 21. PMID: 27653382. * co-corresponding authors.
  • 2) Ghitani N, Barik A, Szczot M, Thompson JH, Li C, Le Pichon CE, Krashes MJ, Chesler AT*.
  • Specialized Mechanosensory Nociceptors Mediating Rapid Responses to Hair Pull. Neuron. 2017 Aug 16;95(4):944-954.e4. doi: 10.1016/j.neuron.2017.07.024. PMID: 28817806. * corresponding author.
  • 3) Szczot M, Liljencrantz J, Ghitani N, Barik A, Lam R, Thompson JH, Bharucha-Goebel D, Saade D, Necaise A, Donkervoort S, Foley AR, Gordon T, Case L, Bushnell MC, Bönnemann CG, Chesler AT*.
  • PIEZO2 mediates injury-induced tactile pain in mice and humans. Science Translational Medicine. 2018 Oct 10;10(462). pii: eaat9892. doi: 10.1126/scitranslmed.aat9892. PMID: 30305456. *corresponding author.
  • 4) von Buchholtz LJ, Ghitani N, Lam RM, Licholai JA, Chesler AT*, Ryba NJP*.
  • Decoding Cellular Mechanisms for Mechanosensory Discrimination. Neuron. 2020 Nov 4:S0896-6273(20)30852-7. doi: 10.1016/j.neuron.2020.10.028. *co-corresponding authors.
  • 5) Marshall KL, Saade D, Ghitani N, Coombs AM, Szczot M, Keller J, Ogata T, Daou I, Stowers LT, Bönnemann CG, Chesler AT*, Patapoutian A*.
  • PIEZO2 in sensory neurons and urothelial cells coordinates urination. Nature. 2020 Oct 14. doi: 10.1038/s41586-020-2830-7 *co-corresponding authors.
  • 6) Case LK, Liljencrantz J, Madian N, Necaise A, Tubbs J, McCall M, Bradson ML, Szczot M, Pitcher MH, Ghitani N, Frangos E, Cole J, Bharucha-Goebel D, Saade D, Ogata T, Donkervoort S, Foley AR, Bönnemann CG, Olausson H, Bushnell MC, Chesler AT.
  • Innocuous pressure sensation requires A-type afferents but not functional ΡΙΕΖΟ2 channels in humans. Nature Communications. 2021 Jan 28;12(1):657. doi: 10.1038/s41467-021-20939-5.
  • 7) Romero LO, Caires R, Nickolls AR, Chesler AT*, Cordero-Morales JF*, Vásquez V*.
  • A dietary fatty acid counteracts neuronal mechanical sensitization. Nature Communications. 2020 Jun 19;11(1):2997. doi: 10.1038/s41467-020-16816-2.PMID: 32561714. *co-corresponding authors.
  • 8) Barik A, Thompson JH, Seltzer M, Ghitani N, Chesler AT*.
  • A Brainstem-Spinal Circuit Controlling Nocifensive Behavior. Neuron. 2018 Dec 19;100(6):1491-1503.e3. doi: 10.1016/j.neuron.2018.10.037. Epub 2018 Nov 15. PMID: 30449655. * corresponding author.
  • 9) Nickolls AR, Lee MM, Espinoza DF, Szczot M, Lam R, Nguyen MQ, Ryba NJ, Ward ME, Zou J, Wang Q, Beers J, Solinski HJ, Hoon MA, AlJanahi AA, Johnson KR, Chesler AT*, Bönnemann CG,*.
  • Transcriptional Programming of Human Mechanosensory Neuron Subtypes. Cell Reports 2020 Jan 21;30(3):932-946.e7. doi: 10.1016/j.celrep.2019.12.062. PMID: 31968264. *co-corresponding author.
  • 10) Szczot M, Pogorzala LA, Solinski HJ, Young L, Yee P, Le Pichon CE, Chesler AT*, Hoon MA*.
  • Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction. Cell Reports. 2017 Dec 5;21(10):2760-2771. doi: 10.1016/j.celrep.2017.11.035. PMID: 29212024. * co-corresponding author.
  • 11) Wlaschin JJ, Gluski JM, Nguyen E, Silberberg H, Thompson JH, Chesler AT*, Le Pichon CE*.
  • Dual leucine zipper kinase is required for mechanical allodynia and microgliosis after nerve injury. Elife. 2018 Jul 3;7. pii: e33910. doi: 10.7554/eLife.33910. PMID: 29968565. * co-corresponding author
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