Candie Paulsen, PhD
Assistant Professor of Molecular Biophysics & BiochemistryCards
About
Titles
Assistant Professor of Molecular Biophysics & Biochemistry
Biography
I love exploring the unknown and the thrill and sense of accomplishment that comes with making the unknown familiar. This passion has inspired me to make significant transitions, both conceptually and with methodology, at every stage of my career. I purposefully choose research projects that serve to improve human health as well as stand to make fundamental discoveries of basic biology and physiology. Moreover, I thoroughly enjoy teaching, mentoring, and helping young scientists find the joy in science. As a graduate student with Kate Carroll at the University of Michigan and The Scripps Research Institute in Jupiter, FL, I studied redox regulation of signal transduction cascades important to cancer. As a postdoctoral fellow with David Julius at the University of California, San Francisco, I determined the first structures of an important pain receptor, TRPA1 by cryo-EM. In the Paulsen Lab, we combine my diverse trainings to take a multidisciplinary approach to understand how TRPA1 is regulated and dysregulated by novel natural variants and through protein-protein interactions. This work is carried out with an eye towards discovering what a pain receptor "sees" in a cellular context, how those molecules can modulate its activity basally, and how those interactions may be modified to contribute to the development of chronic pain/inflammation.
Appointments
Molecular Biophysics and Biochemistry
Assistant ProfessorPrimary
Other Departments & Organizations
- Biochemistry, Quantitative Biology, Biophysics and Structural Biology (BQBS)
- Interdepartmental Neuroscience Program
- Molecular Biophysics and Biochemistry
- Neuroscience Track
- Wu Tsai Institute
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
Education & Training
- Staff Scientist
- Yale University (2017)
- Staff Scientist
- University of California, San Francisco (2017)
- Postdoctoral Fellow
- University of California, San Francisco (2017)
- Postdoctoral Fellow
- The Scripps Research Institute (2012)
- PhD
- University of Michigan, Chemical Biology (2011)
- BS
- Purdue University, Genetic Biology (2006)
Research
Overview
Pain is a fundamental protective mechanism initiated in response to harmful thermal, mechanical, or chemical stimuli that is necessary for survival of a species. When pain sensory neurons become hyper-sensitized, pain can outlive its protective utility and become chronic and debilitating. 100 million Americans suffer from chronic pain, yet, little progress has been made to develop new pain remedies beyond non-steroidal anti-inflammatory agents and opioids, which harbor significant side effects and the risk of addiction. The wasabi receptor, TRPA1, is a non-selective homotetrameric cation channel expressed in primary pain sensory neurons where its activation by diverse chemical irritants initiates pain signals and neurogenic inflammation. This central role of TRPA1 in initiating and enhancing pain signaling through neurogenic inflammation has deemed it a gatekeeper to the development of chronic pain and mark it a viable target for new pain therapeutics. Despite its importance, there is much we do not understand about how TRPA1 is regulated, how it becomes hyper-activated, and how hyper-activated TRPA1 uniquely contributes to the development of chronic pain. Our current research program focuses on determining how TRPA1 is regulated by proteins, lipids, and small molecules and how modifications to those regulatory mechanisms contribute to channel hypersensitivity and aberrant pain signaling. To answer these questions, we employ a multidisciplinary approach that includes chemical biology, molecular biology, protein biochemistry, ion channel electrophysiology, and single-particle electron cryo-microscopy.
Academic Achievements & Community Involvement
Links
Media
- Three-dimensional structure of the ion channel, TRPA1, which is activated by many environmental and endogenous irritants including the active ingredients in wasabi, mustard, onions and garlic to initiate pain sensations. TRPA1 assembles as a homotetramer (each subunit is shown in a distinct color for clarity) in the plasma membrane of a subset of sensory neurons. During her postdoctoral studies, Prof. Paulsen (Yale, MB&B) used a biophysical method called electron cryo-microscopy to solve this first-ever structure of the TRPA1 ion channel. The structure is docked in the density map (grey) to illustrate the high-resolution portion of the ion channel. TRPA1 contains 16 ankyrin repeats, a common protein fold, 11 of which were poorly resolved in the density, but are docked below the core of the channel for completion. The structure revealed, for the first time, the binding site of a necessary cofactor, InsP6 (chemical structure near center).