Genetic variation underlying human transcription factor and cell signaling protein levels.

摘要

Proteomics is an important area to develop to connect common and rare genetic variation to phenotypic variation, from complex trait risks to quantitative traits such as height and response to anticancer agents to gene regulation. Here, I discuss the extension of targeted, antibody-based proteomic platforms to begin to address this question in human cell lines. In Chapter 1, I will discuss the history of antibody-based "protein-omic" platforms, the development of the microwestern array, and my work on extending it to quantify hundreds of proteins across a population of cell lines. In Chapter 2, I will describe the first application of this technology to identify genetic variants associated with transcription factor and cell signaling protein levels and comparing these genetic determinants of protein expression to genetic determines of mRNA expression and complex disease risk. In Chapter 3, I will discuss the integration of cellular responses to chemotherapeutic agents and the identification and validation of novel protein and genetic biomarkers underlying these responses. Lastly, I will conclude with some brief anecdotes on ongoing and future projects that have derived from this thesis work.