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Arthur Salomon, PhD

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Arthur Salomon

Title: Associate Professor of Biology and Chemistry
Department: Molecular Biology, Cell Biology, & Biochemistry and Chemistry

Arthur_Salomon@brown.edu
+1 401 863 6091

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Overview | Research | Grants/Awards | Teaching | Publications

My interests include: elucidation of signaling networks relevant to human disease and exploring perturbations in phosphorylation patterns induced by pharmacological agents. Recently I described a mass spectrometric-based technique that allows efficient profiling of hundreds of phosphorylation sites over time from human total cellular lysates. This technique will be automated by implementation of a high-throughput phosphoproteomics platform to determine global cellular phosphorylation patterns. I intend to employ this platform to map complex signaling networks under normal and pathological conditions.

Biography

Dr. Salomon did undergraduate studies at Case Western Reserve University, graduate studies at Stanford University, and postdoctoral studies at the Genomics Institute of the Novartis Research Foundation. He recently joined the faculty of Brown University where he is Assistant Professor of Molecular Biology, Cell Biology, and Biochemistry (MCB).

Institutions

SS

Research Description

The reversible phosphorylation of tyrosine, serine, and threonine residues is an important mechanism for modulating biological processes such as cellular signaling, differentiation, and growth. A comprehensive understanding of these dynamic cellular processes at the molecular level requires the simultaneous detection of changes in the sites and levels of phosphorylation across numerous proteins over time and through space within the cell. We employ fully automated, highly selective new methodologies that allow for the simultaneous assignment of the temporal and spatial pattern of phosphorylation sites from exceedingly complex mixtures derived from whole cell lysates. This technological infrastructure is applied to the analysis of complex signaling networks in diverse biological and pharmacological contexts.

Many cellular processes are directly controlled through the reversible phosphorylation of protein tyrosine residues. These regulatory functions are ultimately achieved through the coordinated phosphorylation and dephosphorylation of numerous tyrosine residues across multiple proteins over time. Clearly, benefits arise from individually characterizing specific components of a particular pathway, such as identifying a site of phosphorylation on a given protein, the kinase responsible for the modification, or the phosphatase responsible for its removal, or the identity of proteins that subsequently interact. Ultimately though, a thorough understanding of these signaling pathways at the molecular level requires the thorough, simultaneous evaluation of all phosphorylation and dephosphorylation events—changes in phosphorylation state—over time.

Emerging methodologies in mass spectrometry derive their utility through application to persistent, difficult problems in pharmacology and cellular biology. The ability of the mass spectrometer to assign sites of phosphorylation and ubiquitination in complex mixtures of peptides represents an opportunity to greatly accelerate the elucidation of signaling pathways. Identification of novel signaling pathway members will provide targets for rational development of drugs that selectively inhibit these pathways. Recent successes with the BCR/ABL kinase inhibitor STI571 (Gleevec) in the treatment of chronic myelogenous leukemia and with the HER2 receptor protein tyrosine kinase inhibitor Herceptin in the treatment of advanced breast cancer, illustrate the viability of targeting signaling pathway members to treat disease.

Awards

National Institutes of Health Biotechnology Training Grant, 1995-1997
NIH Study Section ZRG1 BST-D(55) National Technology Centers for Networks and Pathways, 2005
NIH Study Section ZRG1 BST-D(51) Continued Development and Maintenance of Software, 2006
Beckman Young Investigator Award, 2006-20010
Session Chair, 96th American Association of Immunologist Annual Meeting "Technological Innovations in Immunology", Seattle, WA, 2009

Affiliations

American Chemistry Society
The American Association of Immunologists

Funded Research

National Institutes of Health Centers of Biomedical Research Excellence (NIH COBRE)
grant #2P20RR015578 (PI: J. Sedivy) 07/01/2005 to 06/30/2010
"Center for Cancer Signaling Networks"
Program Project 3:"High-throughput Proteomic Analysis of Signaling Pathways"

Beckman Young Investigator Award 09/01/2006 to 09/01/2010
Beckman Foundation
"Phosphoproteomic analysis of cellular signaling pathways in allergy and asthma"

R21 AI083908-01 (PI: A. Salomon) 07/17/09 to 06/30/11
NIH/NIAID
"Towards a Molecular Signature of Neutrophil Priming"
The goal of this proposal is the analysis of signaling pathways in human neutrophil priming utilizing novel phosphoproteomic techniques developed in our lab.
Role: PI 10% effort

Teaching Experience

I periodically give lectures covering biological, chemical, and statistical cutting edge proteomic technologies at Brown. In the past this lecture has been integrated into a variety of courses including Bio121, Bio201a, Bio127/227, Bio213, Stats206, Bio154, BC0261, Chem156, CS296, and Phys2620F. I have also taught a seminar course on Topics in Developmental Biology (Bio232) in 2006 and Current Topics in Biochemistry and Molecular Biology: Molecular Mechanisms in Signal Transduction (Bio221) in 2006,7,8. I am presently teaching Introductory Biochemistry (Bio28).

Selected Publications

  • K. Yu, A. Salomon (2010). " HTAPP: High-throughput autonomous proteomic pipeline." Proteomics, In Press.(2010)
  • A. Ritz, G. Shakhnarovich, A. Salomon, B. Raphael (2009). "Discovery of phosphorylation motif mixtures in phosphoproteomics data." Bioinformatics. 25 (1) 14-21.(2009)
  • J. Pezza, S. Langseth, R. Yamamoto, S. Dorris, S. Ulin, A. Salomon, T. Serio (2009). "The NatA acetyltransferase couples Sup35 prion complexes to the [PSI+] phenotype." Molec. Biol. Cell., 20(3): 1068-80.(2009)
  • I. Lee, A. Salomon, K. Yu, L. Samavati, P. Pecina, A. Pecinova, M. Huttemann (2009). "Isolation of regulatory-competent, phosphorylated cytochrome c oxidase." Methods Enzymol, 457, 193-210.(2009)
  • K. Yu, A. Sabelli, L. DeKeukelaere, R. Park, S. Sindi, CA. Gatsonis, A. Salomon (2009). "Integrated platform for manual and high-throuput statistical validation of tadem mass spectra." Proteomics, 9(11), 3115-25.(2009)
  • V. Nguyen, L. Cao, J. T. Lin, N. Hung, A. Rit, K. Yu, R. Jianu, B.J. Raphael, S. Ulin, D.H. Laidlaw, L. Brossay, A. Salomon (2009). "A new approach for quantitative phosphoproteomic dissection of signaling pathways applied to T cell receptor activation." Mol. Cell. Proteomics. 8:2418-31.(2009)
  • K. Yu, A. Salomon (2009). "PeptideDepot: Flexible relational database for visual analysis of quantitative proteomic data and integration of existing protein information." Proteomics, 9(23):5350-8.(2009)
  • R. Jianu, K. Yu, L. Cao, V. Nguyen, A. Salomon, D. Laidlaw (2009). "Effective visual integration of quantitative proteomic data, pathways, and protein information." Trans. on Vis. and Comp. Graphics., In Press.(2009)
  • H. Yu, I. Lee, A. Salomon, K. Yu, M. Huttmann (2008). "Mammalian liver cytochrome c is tyrosine-48 phosphorylated in vivo, inhibiting mitochondrial respiration." Biochim. Biophys. Acta. 1777(7-8) 1066-71.(2008)
  • T. Nuhse, K. Yu, A. Salomon (2007). "Isolation of Phosphopeptides by Immobilized Metal Ion Affinity Chromatography."  In Cur. Prot. Mol. Biol., (Ausubel et al., eds.) 18.13.1-18.13.23. John Wiley & Sons, Hoboken, N.J.(2007)
  • L. Cao, K. Yu, C. Banh, V. Nguyen, A. Ritz, B. Raphael, Y. Kawakami, T. Kawakami, A. Salomon (2007). "Quantitative Time-Resolved Phosphoproteomic Analysis of Mast Cell Signaling." J. Immunology. 179(9) 5864-76.(2007)
  • I. Lee, A. Salomon, K. Yu, J. Doan, L. Grossman, M. Huttemann (2006). "New Prospects for an Old Enzyme: Mammalian Cytochrome c Is Tyrosine Phosphoryalted In Vivo." Biochemistry. 45(30): 9121-9128.(2006)
  • L. Cao, K. Yu, A. Salomon (2006). "Phosphoproteomic Analysis of Lymphocyte Signalling." In Advances in Experimental Medicine and Biology, Vol. 584, C. Tsoukas, ed. Springer, New York, NY. chapter 19, Pgs. 277-88.(2006)
  • S. Ficarro, A. Salomon, L. Brill, D. Mason, M. Stettler-Gill, A. Brock, E. Peters (2005). "Automated immobilized metal affinity chromatography/nano-LC electrospray ionization mass spectrometry platform for profiling protein phosphorylation sites." Rap. Comm. Mass Spec. 19(1):57-71.(2005)
  • I. Lee, A. Salomon, S. Ficarro, I. Mathes, F. Lottspeich, L. Grossman, M. Huttemann (2005). "cAMP-dependent tyrosine phosphorylation of subunit I inhibits cytochrome c oxidase activity." J. Biol. Chem. 280(7): 6094-6100.(2005)
  • L. Brill, A. Salomon, S. Ficarro, M. Mukherji, M. Stettler-Gill, E. Peters (2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Anal. Chem. 76(10): 2763-2772.(2004)
  • A. Brock, D. Horn, E. Peters, C. Shaw, C. Ericson, Q. Phung, A. Salomon (2003). "An automated matrix-assisted laser desorption/ionization quadrupole fourier transform ion cyclotron resonance mass spectrometer for 'bottom up' proteomics." Anal. Chem. 75(14):3419-3428.(2003)
  • C. Ericson, Q. Phung, D. Horn, E. Peters, J. Fitchett, S. Ficarro, A. Salomon, L. Brill, A. Brock (2003). "An automated noncontact deposition interface for liquid chromatography matrix-assisted laser desorption/ionization mass spectrometry." Anal. Chem. 75(10): 2309-2315.(2003)
  • A. Salomon, S. Ficarro, L. Brill, A. Brinker, Q. Phung, C. Ericson, K. Sauer, D. Horn, P. Schultz, E. Peters (2003). "Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry." Proc. Nat. Acad. Sci., 100(2): 443-448.(2003)
  • E. Peters, A. Brock, Q. Phung, J. Fitchett, D. Horn, C. Ericson, S. Ficarro, A. Salomon (2002). "Automated Liquid Chromatography MALDI FT-ICR MS Platform for Proteomics: Rationale for an Off-Line Approach and Optimized Implementation" Am. Pharma. Rev., 5(3): 72-81.(2002)
  • A. Brock, D. Horn, C. Shaw, E. Peters, C. Ericson, Q. Phung, S. Ficarro, A. Salomon (2002). "FT-ICR MS Platform for Proteomics: Automated High Performance Mass Spectrometry and Data Analysis" Am. Pharma. Rev., 5(4): 94-99.(2002)
  • E. Peters, A. Brock, D. Horn, Q. Phung, C. Ericson, A. Salomon, S. Ficarro, L. Brill (2002). "An automated LC-MALDI FT-ICR MS platform for high-throughput proteomics." LCGC Europe, 15(7): 423-8.(2002)
  • J. Pennington, H. Williams, A. Salomon, G. Sulikowski (2002). "Toward a stable apoptolidin derivative: Identification of isoapoptolidin and selective deglycosylation of apoptolidin." Organic Letters, 4(22): 3823-3825.(2002)
  • A. Salomon, Y. Zhang, H. Seto, C. Khosla (2001). "Structure-activity relationships within a family of selectively cytotoxic macrolide natural products." Organic Letters, 3(1): 57-59.(2001)
  • A. Salomon, D. Voehringer, L. Herzenberg, C. Khosla (2001). "Apoptolidin, a selective cytotoxic agent, is an inhibitor of F0F1-ATPase." Chemistry and Biology, 8(1): 71-80.(2001)
  • A.Salomon, D. Voehringer, L. Herzenberg, C. Khosla (2000). "Understanding and exploiting the mechanistic basis for selectivity of polyketide inhibitors of F0F1-ATPase." Proc. Nat. Acad. Sci., 97(26): 14766-71.(2000)
  • H. Zeng, H. Shao, N. Menon, J. Yang, A. Salomon, R. Freidland, and M. Zagorski (2000). "Nicotine and Amyloid Formation" Biological Psychiatry 49(3): 248-257.(2000)
  • A. Salomon, K. Marcinowski, R. Friedland, and M. Zagorski (1996). "Nicotine inhibits amyloid formation by the beta-peptide." Biochemistry 35(42):13568-78.(1996)