Structural Biology Program
The Melinda Diver Lab
The Diver laboratory focuses on ion channels, and other membrane-embedded proteins, involved in somatosensation and pain signaling. The sensation of pain protects our bodies from harm, but maladaptive changes in this sensory modality can lead to debilitating persistent pain disorders. We aim to enhance our biophysical and molecular understanding of sensory transduction and pain sensation and, specifically, how modulation of ion channels in primary afferent somatosensory neurons contributes to chronic pain. Thus, a major goal of ours is to determine mechanisms whereby tissue injury and inflammation enhance the sensitivity of primary afferent nociceptors to noxious (hyperalgesia) and innocuous (allodynia) stimuli. Another important goal of ours is to visualize these ion channels in more physiological environments – an absolute necessity for bridging the disconnect between in vitro membrane protein studies and human disease.
Our broad and innovative approach exploits a range of scale, spanning from tissues to cells to high-resolution structures. By exploiting structural approaches, we explore how sensory ion channels detect a wide range of physical and chemical stimuli, and how they integrate these stimuli to play critical roles in pathophysiology. We focus on questions concerning mechanisms and consequences of lipid-protein and protein-protein interactions and their effects on structure, biophysics, and physiology. As merely solving a structure provides only a superficial understanding of a protein’s function, we emphasize complementary techniques that provide a more complete understanding of function and how it relates to human biology and therapeutics. Fully comprehending the complexities of sensory ion channels, and their regulatory partners, is critical to developing novel, non-opioid analgesics to improve the quality of life for those suffering from chronic pain.
Diver, M.M., Lin King, J.V., Julius, D. and Cheng, Y. (2022). Sensory TRP channels in three dimensions. Annu. Rev. Biochem. 91, 629-649.
Diver, M.M., Cheng, Y. and Julius, D. (2019). Structural insights into TRPM8 inhibition and desensitization. Science 365, 1434-1440.
Diver, M.M., Pedi, L., Koide, A., Koide, S. and Long, S.B. (2018). Atomic structure of the eukaryotic intramembrane RAS methyltransferase ICMT. Nature 553, 526-529.
Diver, M.M. and Long, S.B. (2014). Mutational analysis of the integral membrane methyltransferase isoprenylcysteine carboxyl methyltransferase (ICMT) reveals potential substrate binding sites. J. Biol. Chem. 289, 26007-26020.
Melinda M. Diver, PhD
- The Diver laboratory aims to enhance our biophysical and molecular understanding of sensory transduction and pain sensation and, specifically, how modulation of ion channels in primary afferent somatosensory neurons contributes to chronic pain.
- BSc, Biochemistry, University of British Columbia (2007)
- PhD, Biochemistry and Structural Biology, Weill Cornell Graduate School of Medical Sciences (2015)
- Postdoc, University of California, San Francisco (2021)
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- BA, Biological Sciences (Microbiology) & Theater and Performance Studies, University of Chicago (2021)
- BA, Writing and Rhetoric, Asian Languages and Cultures, Hobart and William Smith Colleges (2011)
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- BA, Biochemistry, Vassar College (Expected 2024)
- BA, Chemistry, Bard College (2022)
- BAc, Economics, Peking University (2013)
- BSc, Biological Sciences, Peking University (2013)
- PhD, Structural Biology/Biochemistry, Peking University (2018)
- Josie Robertson Investigator (2021-2026)
- NCCIH Pathway to Independence Award (K99/R00) (2019-2024)
- A. P. Giannini Postdoctoral Fellowship and Career Award (2017-2019)
- American Heart Association Pre-doctoral Fellowship (2012-2013)
- Dorris J. Hutchinson Fellowship (2010-2011)
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Melinda M. Diver discloses the following relationships and financial interests:
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