Current Projects

Global analysis of protein homeostasis

A central focus of the lab is the development of novel mass spectrometry-based methodologies for system-wide analyses of protein homeostasis. Specifically, we are developing novel techniques for measuring the kinetics of protein degradation, folding, stability and oxidation on proteome-wide scales. These projects are being conducted in collaboration with the University of Rochester Mass Spectrometry Resource Laboratory.

Selected Recent Publications:
"Proteome birthdating reveals age-selectivity of protein ubiquitination." bioRxiv 2024
"Folding stabilities of ribosome-bound nascent polypeptides probed by mass spectrometry." Proc Natl Acad Sci 2023
"Global analysis of methionine oxidation provides a census of folding stabilities for the human proteome." Proc Natl Acad Sci 2019

Methionine redox biology

Methionine residues are prone to oxidation and are converted to methionine sulfoxides by reacting with reactive oxygen species. Oxidized methionines can be enzymatically repaired through the action of a conserved class of enzymes known as methionine sulfoxide reductases (Msrs). Our laboratory is developing methods to investigate methionine redox on proteome-wide scales and identifying factors that regulate the oxidation and reduction of methionines.

Selected Recent Publications:
"Formylation facilitates the reduction of oxidized initiator methionines." bioRxiv 2024
"Protein folding stabilities are a major determinant of oxidation rates for buried methionine residues." J Biol Chem. 2022
"Quantitative analysis of in vivo methionine oxidation of the human proteome." J Proteome Res. 2020

Proteostasis and aging

We are using proteomics to investigate the relationship between protein quality control and aging. By conducting analyses of proteome degradation kinetics across multiple species, we have identified correlations between protein turnover rates and organismal lifespan. We are currently conducting experiments to investigate the link between protein turnover, protein damage and aging.

Selected Recent Publications:
"Accurate proteome-wide measurement of methionine oxidation in aging mouse brains." J Proteome Res. 2022
"Interspecies differences in proteome turnover kinetics are correlated with lifespans and energetic demands." Mol Cell Proteomics 2020
"Cross-species comparison of proteome turnover kinetics." Mol Cell Proteomics 2018

The toxicity of prion aggregates

Accumulation of protein aggregates are generally toxic to cells. Yet, the exact mechanism of toxicity for many types of protein aggregates remain incompletely understood. We are investigating the toxic mechanism of prion protein aggregates that accumulate during the course of prion diseases such as Creutzfeldt Jakob Disease. These aggregates tend to accumulate in the endocytic pathway within prion infected cells and are highly toxic to neurons. Yet, many other cell types (e.g. neuroblastomas) can accumulate prion aggregates without any signs of overt toxicity. Our lab is trying to uncover the exact cellular mechanisms that make some cells resistant to the toxic effects of prions.

Selected Recent Publication:
"Global analysis of protein degradation in prion infected cells." Sci. Rep. 2020
"Methionine oxidation within the prion protein." Prion 2020