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Adam R. Simard

Education and Experience
Ph.D. Candidate, Dartmouth College
B.S., Microbiology, University of Maine, Orono. 2015

  • Research Associate, Mascoma LLC. 2015 - 2019
  • Undergraduate Researcher, University of Maine, Orono. 2014 - 2015

Joined the 'Mad-den' in 2020

Contact
adam.r.simard.gr@dartmouth.edu
LinkedIn

Research Summary

Cif is a homodimeric epoxide hydrolase produced by the lung pathogen Pseudomonas aeruginosa and exhibits virulence properties that are of concern for persons with cystic fibrosis (CF). Once delivered to the airway epithelia via outer membrane vesicles, Cif causes a rapid decrease in apical CFTR and threatens to undermine the therapeutic benefit of modulator therapies. Cif also promotes a hyper-inflammatory environment by destroying 14,15-epoxyeicosatreinoic acid, a transcellular signaling molecule involved in the regulation of neutrophil recruitment. This bifurcated assault amplifies the lung pathophysiology afflicting CF patients. Using X-ray crystallography and biochemical assays, I study the finer details pertaining to Cif and it’s interaction with various molecules including substrates, nanobodies, and inhibitors. By studying how these interactions augment Cif activity, we hope to refine our understanding of the mechanics of cooperative and allosteric regulation in this enzyme. And with a little luck, maybe we can make a move at a therapeutic that could help a person or two.