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From Collaboration to Clinic

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Few recommendations come higher than from people who have made the very choice they’re advocating. When Josh Mendell, a scientist and researcher at the Institute of Genetic Medicine at Johns Hopkins, says that his institute offers “a great environment,” you can be sure he believes it — because when he had the chance to go off to another setting after his postdoctoral work there, he instead leaped at the opportunity to take a faculty position within the institute.

Mendell’s lab focuses on the role played by microRNAs in cancer. “It’s become clear that microRNA expression patterns are almost always abnormal in cancer cells compared to normal cells from the same tissue,” he says. Add to that findings that “specific microRNAs … have been found that can act as a new oncogene or tumor suppressor” and Mendell certainly has a ripe field for his studies. He hopes that he and his team can better understand just how microRNAs are implicated in cancer, and whether RNA interference offers hope of novel therapy for the disease.

No doubt he’s in a good position for these pursuits; one critical component of IGM — and a relatively rare one among systems biology-style institutes — is its direct connection to clinical research and treatment. “There are much closer ties between basic scientists and clinicians,” says Aravinda Chakravarti, the institute’s inaugural director who stepped down earlier this year to run a center within IGM. “It’s a unique kind of atmosphere.”

That clinical work will be of increasing importance in the coming years, says new director David Valle. “We will continue to expand our clinical activities — particularly as the role of the genes becomes more obvious for all kinds of disorders — to assist our colleagues in all of the clinical departments here at the school,” he says. In addition to direct ties with patient research and treatment, clinically oriented programs at IGM include “an active program of genetic counselors” and other service programs, Valle says.

At Hopkins, like other academic institutions, the value of a clinical tie was not always an easy case to make, Chakravarti recalls. The current esteem with which research faculty see their links to actual patients has been a long time coming. “Clinical work … [was] valued only in name,” Chakravarti says of the attitude in research organizations in years past. “At any of the leading institutions, that wasn’t really the quickest path or even the most successful path to professional accolade or tenure. NIH funding was minimal for people who did clinical work.” As he sees it, the problem boiled down to one of commitment. “[People ask] why has translational research been so far behind,” Chakravarti says. “I think the major reason is that we as a community didn’t put our money where our mouth is.”

Times certainly have changed, Chakravarti says. “Many of the right changes have happened. It really is a path for tenure, promotion, and recognition.” In other words, the landscape has shifted enough to allow a research-meets-clinic institute like IGM to find real success.

The Joy of Teamwork

Clearly, the success of research-clinic work is predicated on scientists’ ability to collaborate. But ask an IGM member for an explanation of how the institute fosters these kinds of collaborations, and in all likelihood you’ll get little more than silence. Fact is, the team-building spirit at IGM is strong enough that the leadership has never had to think about formal ways of encouraging partnerships.

“People who have been here for ages will tell you one of the key features of Hopkins is the highly collaborative nature of the faculty,” says Chakravarti. “It’s something that’s part of the culture.”

Mendell says his lab is involved in a number of projects with other groups around the institute and the school as a whole. “People are always working together across labs,” he says. That has proven to be a tremendous boon for interdisciplinary and cross-technology research. “There’s a wide range of expertise and research that’s being done and model systems that are being used,” Mendell says of the work at IGM, citing as examples research from zebrafish to mice to classic human genetics, performed with technologies ranging from RNA biology to proteomics. “That creates a really stimulating environment, and I think it helps us think about different ways to approach problems,” he says.

With teamwork like that, who needs a formal institute? According to Chakravarti, who served as the first director for IGM, the Hopkins genetics faculty needed to be pushed just a little. “Genetics, and primarily human genetics and medical genetics, has been here at Hopkins and successful for over 50 years,” he says. “Genetics was spread out over so many departments here. … While genetics was being rejuvenated everywhere else, it wasn’t being done here.” So in January 1999, IGM was officially launched as a way to establish a “central place where we could relight the fire,” Chakravarti says.

To ensure the institute was a dynamic place without the walls and boundaries typical of academic departments, the single rule Chakravarti was given as he took the helm of IGM was that every institute member had to have a primary affiliation in a regular department, he recalls. In practice, IGM is home base for the roughly 35 faculty members who are very involved in the institute: “This is where our physical space is, where all of our budgets and grants go through; we make tenure decisions here,” Chakravarti says. Another 40 or 45 faculty members have affiliations with IGM, but don’t call it home.

While the institute began in concept more than seven years ago, it’s only for the last two and a half years or so that IGM scientists have been rounded up in the same building. Chakravarti says over that time there’s been a significant push to bring in researchers with very diverse interests — “proteomics, microRNA work, highly conserved noncoding regions” — to the institute. That, in addition to being in the same building, has helped fuel even more collaborations.

With the institute already making its mark in research and the clinical realm, new director Valle says the next push will be in the educational arena. Hopkins is in the midst of establishing a new curriculum called Genes to Society, and “we hope to play a very major role in thinking about that curriculum,” Valle says.

Name: McKusick-Nathans Institute of Genetic Medicine

Host: Johns Hopkins Medicine

Director: David Valle

Established: January 1999

Staff: The institute has nearly 40 core faculty members, and another 50-some affiliated faculty members. Overall, there are more than 300 employees and about 50 graduate students at IGM.

Funding: According to former director Aravinda Chakravarti, the institute was established with money from the Hopkins School of Medicine as well as philanthropic gifts and endowments. The institute also has a significant amount of money from federally funded grants and contracts through its faculty members.

Research efforts: Studies led by IGM members run the gamut from genomics and gene regulation to computational biology to genetic epidemiology and clinical research.

Core facilities: Core labs support a number of services, including DNA sequencing and synthesis; genotyping; cell culture work; and more.

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