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The Protein Perspective on Cancer

  • Title: Assistant Professor, Dana-Farber Cancer Institute and Harvard Medical School
  • Education: PhD, Ohio State University, 1995
  • Recommended by: Paul Morrison

The Dana-Farber Cancer Institute’s Jarrod Marto aims to put cancer in context. As head of the recently inaugurated $16.5 million proteomics center at the institute, Marto works on isolating proteins involved in cancer-related events. Using high-throughput proteomics and mass spec, he’s hoping, for example, to find proteins involved in downstream signaling of oncogenetic kinases or to find protein complexes involved in the DNA damage response. In any case, it’s “where you’re trying to watch response of either changes in phosphorylation or changes in protein complex membership as a function of biological perturbation,” Marto says. “We’re primarily a mass spectrometry-based laboratory, so we’re keen on the stable isotope labels for the quantitative studies.”

Marto completed his PhD in analytical chemistry at Ohio State University in Columbus, Ohio. He did a postdoc at the University of Virginia, where he became a member of the research faculty. He was then appointed director of analytical proteomics for MDS Proteomics in Charlottesville, Va., before coming to Dana-Farber. It was, however, his undergraduate days that sparked his fire for molecules and how they interact with one another. “I was always attracted to the quantitative sciences, physical sciences,” he says. He spent a few summers doing research internships, “and that really got me kind of hooked.”

Looking ahead

Some of the biggest challenges facing the field in the future, Marto believes, are the limitations of today’s mass spec instruments in affording detection of a wide dynamic range. Teasing out the low-abundance proteins — the important ones when it comes to cancer signaling cascades — from the wide dynamic range of the pool is the biggest challenge. “I think the classic example is, the plasma proteome is estimated to contain proteins that span a concentration dynamic range of 11 orders of magnitude,” Marto says. “And the huge limitation is that you can’t detect simultaneously across that entire abundance range. It turns out to be one of the huge limitations in the field of proteomics.”

Some of the workarounds Marto has been using include enriching protein classes of interest, industrial collab-orations to improve the instrumentation itself, and developing better algorithms to both analyze the increasingly complex and large amounts of proteomics data as well as to follow up on the most important subsets of these data. “Like many people in the field, we’ve been working with a combination of commercial and open source tools to do this and, in fact, we have our own internal effort primarily aimed at … portable and lightweight desktop applications.”

One area he sees as being necessary for the field’s forward momentum is large-scale data management projects like that of HUPO. “I think it’s very clear that the field is moving beyond the concept of generating catalogs of proteins and [it] clearly needs to get to a point where there is some standardization in [quantitative] measurements and some robust mechanism for distribution or sharing of data.”

Publications of note

A recent paper published in the October 2006 issue of the Journal of Proteome Research (“Improved immobilized metal affinity chromatography for large-scale phosphoproteomics applications”) takes on high-throughput identification of phosphopeptides in a complex biological sample using immobilized metal affinity chromatography.

Leadership style

With a staff of 12 in his lab, he takes pride in the integrity his team brings to the research. “My particular approach is [to] focus on getting high-quality people who really embrace the idea of cross-disciplinary research and propose a number of intriguing research questions — and then give them the resources they need and the freedom they need to get the work done.”

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