Todd Greco

2022-12-03

Todd Greco Todd Greco  Ph.D. As a senior scientist in the laboratory of Ileana Cristea at Princeton University, his research focuses on understanding the contribution of proteome dynamics to pathological states, including virus infection and neurodegenerative diseases. A primary goal is to accelerate the identification of disease-relevant proteins by combining multiple proteomic perspectives from a single model system. Using quantitative mass spectrometry-based proteomics, paired with molecular and optical approaches, Todd gains insight into the temporal dynamics of protein abundance, localization, protein complexes, and post-translational modifications. Moreover, he employs IDIRT-based AP-MS workflows to monitor protein interaction abundance and stability, which are suitable for global and targeted MS studies. In the proteomics community, Todd regularly teach Ph.D. candidates and facility staff about MS experimental design and software, including Skyline and Proteome Discoverer.

Unbiased and Targeted Mass Spectrometry Provides Insight into Huntington’s Disease Pathogenesis

The causative agent of Huntington’s disease (HD) is the CAG repeat expansion of the huntingtin gene, producing a mutant protein with an expanded glutamine tract (mHTT). mHTT toxicity selectively impacts the brain and liver. mHTT-induced proteome and protein interaction alterations have been investigated in the brain, yet those proximal to disease progression remain poorly understood. Read More
Moreover, the molecular signatures of mHTT toxicity in the liver are unknown. In HD mouse models from pre-symptomatic and post-symptomatic stages, we explored polyQ- and age-dependent relative stabilities of mHTT protein interactions using AP-MS and 13C-labeled tissues. mHTT caused increased protein interaction stabilities, while specific components of phosphorylation signaling networks were impacted. Additionally, we detected 219 differential protein candidates in mHTT liver using MS1-based LFQ, which were all targeted for validation by PRM using Skyline. This provided large scale validation of HTT disease- and tissue-specific altered protein abundances.


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