• Researcher Profile

    Jarrod Marto, PhD

     
    Jarrod Marto, PhD
     
    Associate Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School

    Office phone: 617-632-3150
    Fax: 617-582-7737
    Email: jarrod_marto@dfci.harvard.edu

    Preferred contact method: email
     
     

    Research Department

    Cancer Biology

    Area of Research

    Using Proteomics to Analyze the Molecular Events of Tumorigenesis

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Smith 1158
    Boston, MA 02215

    Biography

    Jarrod Marto received his PhD in analytical chemistry from The Ohio State University in Columbus, Ohio. Following his postdoctoral work at the University of Virginia, he became a member of the research faculty there. He then was named a senior research scientist and the director of analytical proteomics for MDS Proteomics in Charlottesville, VA. Dr. Marto recently joined the staff of DFCI to continue his research of proteomics-based techniques in protein expression and signaling events relevant to cancer initiation and progression.

    Research

    Using Proteomics to Analyze the Molecular Events of Tumorigenesis

    Our lab is focused on the development and application of proteomics-based methods for in-depth analysis of key molecular events in tumorigenesis. The overall thesis supporting this work is that cellular control of biological processes, such as differentiation, occurs primarily at the level of multiprotein complexes and is orchestrated through a delicate balance of protein-protein interactions and posttranslational modifications. Intervention or manipulation intended to achieve a desired biological outcome requires deciphering the individual events that collectively contribute to a particular cellular state.

    Given the highly dynamic nature of biological processes, we are particularly interested in novel and robust strategies for measuring relative changes in both protein expression levels and the posttranslational modification state of the proteome in response to perturbation. Limited dynamic range is a common obstacle encountered during proteomics-driven analyses of complex mixtures; oftentimes, changes in low-abundance proteins are critical to an observed phenotype but are undetectable by proteomics experiments performed in the context of a given biological milieu. We are pursuing a number of different strategies to overcome this hurdle, including: (1) enrichment of protein classes of interest, either through isolation of cell compartments or chromatographic- and affinity-based methods; (2) improved mass spectrometry technology, through internal efforts and via industrial collaboration; and (3) development of novel data processing and bioinformatics algorithms to more efficiently analyze the vast quantity of data generated in global proteomics experiments.

    We currently use cell lines as model systems to query relative protein expression and phosphorylation events critical to aberrant signaling, blocked differentiation, and other functional hallmarks of cancer. In principle, proteomics-based methods provide a highly parallel readout of multiple biologically relevant events in a single experiment. Collectively, these data provide a detailed view of key molecular mechanisms in cancer initiation and progression and can also facilitate drug target discovery and improved characterization of small molecule therapeutics. In the future, we expect to leverage continued improvements in proteomics methods, in combination with other technologies, to transition into analysis of clinical samples and development of new diagnostic protocols to better detect and characterize cancer onset and progression.

    Select Publications

    • Marto JA, Brame CJ, Ficarro SB, White FM, Shabanowitz J, Hunt DF. Sequence analysis: low energy MS/MS- peptide sequence interpretation. In: Gross ML, Caprioli RM, editors. The encyclopedia of mass spectrometry. Boston: Elsevier; 2005. p. 165-76.
    • Syka JE, Marto JA, Bai DL, Horning S, Senko MW, Schwartz JC, Ueberheide B, Garcia B, Busby S, Muratore T, Shabanowitz J, Hunt DF. Novel linear quadrupole ion trap/FT mass spectrometer: performance characterization and use in the comparative analysis of histone H3 post-translational modifications. J Proteome Res 2004;3:621-6.
    • Zarling AL, Luckey CJ, Marto JA, White FM, Brame CJ, Evans AM, Lehner PJ, Cresswell P, Shabanowitz J, Hunt DF, Engelhard VH. Tapasin is a facilitator, not an editor, of class I MHC peptide binding. J Immunol 2003;171:5287-95.
    • Townsend DM, Marto JA, Deng M, Macdonald TJ, Hanigan MH. High pressure liquid chromatography and mass spectrometry characterization of the nephrotoxic biotransformation products of Cisplatin. Drug Metab Dispos 2003;31:705-13.
    • Ficarro S, Chertihin O, Westbrook VA, White F, Jayes F, Kalab P, Marto JA, Shabanowitz J, Herr JC, Hunt DF, Visconti PE. Phosphoproteome analysis of capacitated human sperm. Evidence of tyrosine phosphorylation of a kinase-anchoring protein 3 and valosin-containing protein/p97 during capacitation. J Biol Chem 2003;278:11579-89.

    Trainees

    • PhD, Rositsa Koleva