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INFORMATION FOR

Jesse Rinehart, PhD

Associate Professor

Contact Information

Jesse Rinehart, PhD

Lab Location

Office Location

Mailing Address

  • Systems Biology Institute

    PO Box 27388

    West Haven, CT 06516-7388

    United States

Research Summary

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/

Coauthors

Research Interests

Biochemistry; Biotechnology; Hypertension; Molecular Biology; Phosphoproteins; Signal Transduction; Proteomics; Systems Biology; Synthetic Biology

Research Images

Selected Publications

  • Correction: The mechanism of β-N-methylamino-L-alanine inhibition of tRNA aminoacylation and its impact on misincorporationHan N, Bullwinkle T, Loeb K, Faull K, Mohler K, Rinehart J, Ibba M. Correction: The mechanism of β-N-methylamino-L-alanine inhibition of tRNA aminoacylation and its impact on misincorporation Journal Of Biological Chemistry 2022, 298: 102544. PMCID: PMC9547288, DOI: 10.1016/j.jbc.2022.102544.
  • CSIG-08. TARGETING ION TRANSPORT-REGULATORY KINASES AS A NOVEL TREATMENT FOR GLIOBLASTOMASchiapparelli P, Meade P, Miranda-Herrera P, Bechtle A, Issacs F, Levchenko A, Rinehart J, Quinones-Hinojosa A. CSIG-08. TARGETING ION TRANSPORT-REGULATORY KINASES AS A NOVEL TREATMENT FOR GLIOBLASTOMA Neuro-Oncology 2020, 22: ii29-ii29. PMCID: PMC7650317, DOI: 10.1093/neuonc/noaa215.120.
  • 205-OR: Hepatic Protein Kinase C-e Is Necessary and Sufficient in Mediating Lipid-Induced Hepatic Insulin ResistanceLYU K, ZHANG D, KAHN M, RODRIGUES M, HIRABARA S, LUUKKONEN P, LEE S, BHANOT S, RINEHART J, BLUME N, RASCH M, SERLIE M, BOGAN J, CLINE G, SAMUEL V, SHULMAN G. 205-OR: Hepatic Protein Kinase C-e Is Necessary and Sufficient in Mediating Lipid-Induced Hepatic Insulin Resistance Diabetes 2020, 69 DOI: 10.2337/db20-205-or.
  • The mechanism of β-N-methylamino-l-alanine inhibition of tRNA aminoacylation and its impact on misincorporationHan N, Bullwinkle T, Loeb K, Faull K, Mohler K, Rinehart J, Ibba M. The mechanism of β-N-methylamino-l-alanine inhibition of tRNA aminoacylation and its impact on misincorporation Journal Of Biological Chemistry 2020, 295: 1402-1410. DOI: 10.1016/s0021-9258(17)49898-x.
  • Innentitelbild: Chemische Evolution eines bakteriellen Proteoms (Angew. Chem. 34/2015)Hoesl M, Oehm S, Durkin P, Darmon E, Peil L, Aerni H, Rappsilber J, Rinehart J, Leach D, Söll D, Budisa N. Innentitelbild: Chemische Evolution eines bakteriellen Proteoms (Angew. Chem. 34/2015) Angewandte Chemie 2015, 127: 9862-9862. DOI: 10.1002/ange.201506522.
  • Inside Cover: Chemical Evolution of a Bacterial Proteome (Angew. Chem. Int. Ed. 34/2015)Hoesl M, Oehm S, Durkin P, Darmon E, Peil L, Aerni H, Rappsilber J, Rinehart J, Leach D, Söll D, Budisa N. Inside Cover: Chemical Evolution of a Bacterial Proteome (Angew. Chem. Int. Ed. 34/2015) Angewandte Chemie International Edition 2015, 54: 9726-9726. DOI: 10.1002/anie.201506522.
  • Chemische Evolution eines bakteriellen ProteomsHoesl M, Oehm S, Durkin P, Darmon E, Peil L, Aerni H, Rappsilber J, Rinehart J, Leach D, Söll D, Budisa N. Chemische Evolution eines bakteriellen Proteoms Angewandte Chemie 2015, 127: 10168-10172. DOI: 10.1002/ange.201502868.
  • Src‐family tyrosine kinase (SFK) phosphorylates With‐No‐ Lysine Kinase4 (WNK4) and modulates the inhibitory effect of WNK4 on ROMK channels.Lin D, Yue P, Yarborough O, Lifton R, Rinehart J, Wang W. Src‐family tyrosine kinase (SFK) phosphorylates With‐No‐ Lysine Kinase4 (WNK4) and modulates the inhibitory effect of WNK4 on ROMK channels. The FASEB Journal 2013, 27: 911.2-911.2. DOI: 10.1096/fasebj.27.1_supplement.911.2.
  • Src‐family protein tyrosine kinase (SFK) stimulates KCNJ10 K channels in the basolateral membrane of distal convoluted tubules (DCT).Wang W, Zhang C, Lin D, Yue P, Wang L, Rinehart J. Src‐family protein tyrosine kinase (SFK) stimulates KCNJ10 K channels in the basolateral membrane of distal convoluted tubules (DCT). The FASEB Journal 2013, 27: 911.1-911.1. DOI: 10.1096/fasebj.27.1_supplement.911.1.
  • Sec23b deficiency In Mice Results In Pancreatic Destruction and Defective long Term Hematopoietic Stem Cell FunctionVasievich M, Zhang B, Rinehart J, Jones M, Maillard I, Ginsburg D. Sec23b deficiency In Mice Results In Pancreatic Destruction and Defective long Term Hematopoietic Stem Cell Function Blood 2010, 116: 2038-2038. DOI: 10.1182/blood.v116.21.2038.2038.
  • Sites of Regulated Phosphorylation that Control K-Cl Cotransporter ActivityRinehart J, Maksimova Y, Tanis J, Stone K, Hodson C, Zhang J, Risinger M, Pan W, Wu D, Colangelo C. Sites of Regulated Phosphorylation that Control K-Cl Cotransporter Activity Journal Of End-to-End-testing 2009, 138: 525-536. DOI: 10.1016/s9999-9994(09)20390-4.
  • Sites of Regulated Phosphorylation that Control K-Cl Cotransporter ActivityRinehart J, Maksimova Y, Tanis J, Stone K, Hodson C, Zhang J, Risinger M, Pan W, Wu D, Colangelo C, Forbush B, Joiner C, Gulcicek E, Gallagher P, Lifton R. Sites of Regulated Phosphorylation that Control K-Cl Cotransporter Activity Journal Of End-to-End-testing 2009, 138: 525-536. DOI: 10.1016/s9999-9994(09)20441-7.
  • Structural and Functional Interactions of KCl Cotransport Proteins KCC1 and KCC3 in Sickle and Normal Erythrocyte MembranesRisinger M, Risinger M, Rinehart J, Crable S, Crable S, Ottlinger A, Ottlinger A, Winkelmann R, Winkelmann R, Pan D, Pan D, Huebner C, Huebner C, Gallagher P, Joiner C, Joiner C. Structural and Functional Interactions of KCl Cotransport Proteins KCC1 and KCC3 in Sickle and Normal Erythrocyte Membranes Blood 2008, 112: 2474-2474. DOI: 10.1182/blood.v112.11.2474.2474.
  • A mutation in WNK4 that causes human hypertension activates the epithelial Na+ channel in vivoRing A, Kahle K, Cheng S, Leng Q, Lalioti M, Wilson F, Rinehart J, Hebert S, Lifton R. A mutation in WNK4 that causes human hypertension activates the epithelial Na+ channel in vivo The FASEB Journal 2007, 21: a876-a876. DOI: 10.1096/fasebj.21.6.a876-c.
  • Catalytically‐inactive WNK3 bypasses the tonicity requirement for K‐Cl cotransporter activation via a phosphatase‐dependent pathwayDe los Heros P, Kahle K, Rinehart J, Bobadilla N, San Cristobal P, Vazquez N, Lifton R, Hebert S, Gamba G. Catalytically‐inactive WNK3 bypasses the tonicity requirement for K‐Cl cotransporter activation via a phosphatase‐dependent pathway The FASEB Journal 2006, 20: a1224-a1224. DOI: 10.1096/fasebj.20.5.a1224.
  • Saccharomyces cerevisiae imports the cytosolic pathway for Gln‐tRNA synthesis into the mitochondrionKrett B, Rinehart J, Rubio M, Alfonzo J, Söll D. Saccharomyces cerevisiae imports the cytosolic pathway for Gln‐tRNA synthesis into the mitochondrion The FASEB Journal 2006, 20: a500-a500. DOI: 10.1096/fasebj.20.4.a500-b.