Jesse Rinehart, PhD

Our laboratory is focused on the discovery and characterization of novel sites of phosphorylation in kinases and regulatory networks of proteins that control electrolyte homeostasis. Our long term goal is to understand and “decode” complex signaling networks in physiological systems. Our research integrates cutting edge proteomics with mainstay techniques of molecular biology and physiology, to study signaling networks and provide critical new insight into regulated ion transport. We are focusing on mechanisms of cellular signaling transduction that involve protein phosphorylation. Many of the cellular signaling mechanisms that are disrupted in disease states, and are assumed to be fundamental for normal cellular physiology, are largely uncharacterized and hold a vast amount of therapeutic potential. Understanding the human phosphoproteome is a major challenge as research continues ever farther into the post genome era. We therefore employ established quantitative proteomic techniques, and aim to develop novel methods, in an effort to decode new signaling pathways. We aim to find new roles for kinases, phosphatases, their substrates, and protein-protein interactions on a system-wide level. Collectively, we hope these efforts will identify molecular mechanisms important for both healthy and disease states in humans.

Tens of thousands of phosphorylation sites in diverse eukaryotic proteins have been identified through large scale mass spectrometry studies. For the great majority of these sites, however, the responsible kinase is unknown, and the functional role of phosphorylation is not understood. We have recently made substantial progress towards narrowing this critical gap in knowledge with a new technology that enables site-specific incorporation of phosphoserine into proteins. This technology utilizes an E. coli strain with an expanded genetic code and contains a dedicated sense codon for phosphoserine. We use this breakthrough technology to synthesize human phosphoproteins and accelerate our efforts in “decoding” the human phosphoproteome.

Specialized Terms: Physiological Systems; Protein Phosphorylation; Cell Signaling; Phosphoproteomics; Protein Engineering; Ion Transport; Synthetic Biology; Translational Research

Learn more at http://rinehart.commons.yale.edu/