Inorganic Chemistry Seminar: Professor Katlyn Meier, University of Miami
About the Seminar
"Mechanistic Insights into Metal-Protein Interactions: Implications for Neurodegenerative Disease Progression and Intervention"
Elevated levels of protein expression and aberrant metal exposure have been reported in many neurodegenerative diseases, including Huntington’s Disease (HD). While there is currently no cure for HD, metal chelation therapies have been shown to assuage disease symptoms including chorea. These observations underscore the critical need to understand how metal-protein interactions are involved in disease pathogenesis. Our objective in this work is to elucidate the role of copper (Cu) and other biorelevant metals in HD and, more specifically, their interactions with the huntingtin protein (htt). We aimed to characterize the Cu-htt interaction and speciation trends in our in vitro HD system, as well as the influence of disease-relevant Cu concentrations on protein oligomerization/aggregation both in vitro and in vivo. We utilized multiple spectroscopic techniques (circular dichroism, electron paramagnetic resonance, UV-Vis absorption, dynamic light scattering, and mass spectrometry) that cover a broad range of energy scales, allowing us to characterize protein structure at the molecular, secondary structure, and quaternary structure levels. Additionally, site-directed mutagenesis of several putative metal binding residues was used to define the roles of specific amino acids in mediating oligomerization/aggregation, metal binding, and redox chemistry. Taken together, our work has led to the first report of multiple copper binding sites in non-pathological htt and provides insight into one pathway for depletion of native htt pools that may contribute to HD.
About the Speaker
Katlyn received her B.S. in Physics from Allegheny College in 2009, where she conducted research with Doros Petasis to spectroscopically characterize (via electron paramagnetic resonance, EPR) Fe/Ru spin cross-over complexes. She received her Ph.D. in Physical Chemistry from Carnegie Mellon University in 2015 under the direction of Professor Eckard Münck. During her graduate research, she utilized EPR in combination with variable temperature and variable field (VTVH) Mössbauer spectroscopies and density functional theory (DFT) calculations to define the structural and electronic properties of biological, biomimetic, and synthetic systems involved in O2-activation. After earning her Ph.D., Katlyn went on to join the lab of Professor Edward Solomon at Stanford University as a NIH Ruth L. Kirschstein National Research Service Award (F32) postdoctoral fellow. There, she focused on defining the structures and mechanisms of copper-dependent enzymes including lytic polysaccharide monooxygenases and the formylglycine generating enzyme. During this time, she expanded her expertise to include VTVH magnetic circular dichroism (MCD), circular dichroism (CD), stopped-flow absorption kinetics, and protein expression and purification. Since starting her independent career at the University of Miami in Fall 2019, Katlyn has been named a Frost Junior Research Fellow, and she recently received the 2026 Paul D. Saltman Memorial Award at the Metals in Biology Gordon Research Conference. She’s also received funding support from the Miami Clinical & Translational Science Institute KL2 program for her work to elucidate the interaction of the huntingtin protein with copper and commercially available chelators as well as an NSF CAREER award for her work on defining heme- and non-heme mediated protein-protein interactions and enzyme mechanisms.
Host: Ed Solomon
This seminar is supported by the William S. Johnson endowment honoring this esteemed chemist, who made significant contributions in the areas of synthetic and bioorganic chemistry.