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Nicholas Marko: From Bedside to Bench and Back

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Title: Chief resident, neurosurgery, Cleveland Clinic
Education: MD, George Washington University School of Medicine, 2005
Recommended by: Robert Weil, Cleveland Clinic

Nicholas Marko seeks to determine how best to translate molecular data gleaned from gene expression analyses into clinically relevant classifications to guide the medical management of patients with malignant brain tumors. As chief resident of neurosurgery at the Cleveland Clinic, Marko oversees the surgical and medical management of brain cancer patients — and when he's not in the OR, he's using genomic technologies to guide translational neuro-oncology research.

It was a particularly formative Howard Hughes Medical Institute fellowship at The Institute for Genome Research that Marko calls his "formal entrance into computational and genome biology." He credits TIGR alum John Quackenbush for pushing him to look beyond the confines of his field and "really look toward where you can cross over."

Marko's investigations began at the bedside and have taken him to the genomics bench and back again. He says that his idea of translational research "might be a bit different from how the term [is] often applied" as he says it should begin with a clinical question, evolve into hypothesis-driven basic research, and end with "taking those answers back to the clinic." Marko says that clinician-researchers are "particularly well-suited to participate in and shape translational research."

He adds that "patients in the clinic don't want to know what their RAF pathway looks like. They want to know, 'What kind of treatment am I going to respond to?' and 'How long do I have to live?'"

Though his work is primarily focused on stratifying glioblastoma patients based on their phenotypic profiles, Marko is also working to transform the theoretical foundations and analytic processes that underlie the majority of biomedical studies. In a Science Translational Medicine paper published in November, Marko outlines researchers' needs to consider how data is distributed, recognize that biological systems are non-linear, and consider the role that randomness may play in tumorigenesis and other disease processes.

"What makes the work I do interesting is that it really requires [me] to look outside of the traditional fields," he says, adding that he has borrowed ideas from fields that use non-linear dimensional reduction and dynamic systems modeling, like quantum mechanics, astrophysics, fluid dynamics, and cosmology. "I think we can learn from the experiences of these folks and the techniques they've developed and then we, as cancer biologists, can apply them to cancer. What we'll get is a whole new way to conceptualize these large-volume, molecular data sets."

Looking ahead

In the future, Marko envisions sending post-op patient tumor samples out for timely, whole-genome sequencing and predictive analysis, which "will make a tremendous difference" in patient management, he says.

Publications of note

Marko calls his 2008 Genomics paper, in which he and his Cleveland Clinic colleagues examined the gene expression differences between long- and short-term survivors of glioblastomas, and a 2010 follow-up paper in the same journal, in which the team applied this approach to low-grade gliomas, "solid pieces of genomics work under the current model." It is his recent Science Translational Medicine paper, though, that he considers exemplary. It describes "where I think the science needs to go to really make it work," Marko says.

And the Nobel goes to ...

Were Marko to be awarded the Nobel, he'd want it to be for "translating this spreadsheet full of data I have in front of me into a clinically useful, predictive tool that can guide therapeutic management of patients and really improve their outcomes," he says.

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