Partner and Prosper: Graduate Students Team Up with NIH Investigators

By Simona Patange

Monday, April 4, 2016

A little-known fact about the NIH Intramural Research Program (IRP) is that a Ph.D. student can conduct dissertation research at NIH as a formal partnership with his or her graduate institution. So, how does a graduate institutional partnership with the NIH begin?

An institutional partnership grown from grassroots collaboration

The University of Maryland (UMD)-National Cancer Institute (NCI) Partnership for Integrative Cancer Research began in early 2003 with two scientists up against the limits of their research fields. Dr. Carole Parent, a then new IRP tenure-track investigator in the Center for Cancer Research (CCR) at NCI, was using microscopes to take time-lapse movies of migrating neutrophils and wanted to quantify the behavior she was observing. At the same time, Dr. Wolfgang Losert, a UMD physics professor, was developing algorithms to track shape dynamics of cells and looking to apply them to significant biological questions.

A chance meeting between Parent and Losert made it clear that each had expertise the other needed, and collaboration would be essential to moving both of their projects forward. The discussions were informal at first. “We went to each other’s group meetings to see how we could really help each other,” Parent says. “How could Wolfgang access biological systems, and how could I quantify the movies we were generating of migrating cells?”

In parallel, at a neighborhood picnic in 2005, Dr. David Levens at CCR and Dr. Drew Baden, who was chair of the Department of Physics at the University of Maryland, discussed the synergistic potential of partnering NCI life scientists with the physics, mathematics, and engineering expertise at UMD. Thereafter, Dr. Jim McNally, also at CCR, and Losert were enlisted to help mobilize colleagues and administrators at both institutions to establish collaborations and develop mechanisms to explore how these nascent connections might help them answer their own research questions. In 2006, the first collaborations developed on an ad hoc basis.

There were major administrative hurdles to inviting UMD graduate students to NCI, one being concerns of intellectual property, but in 2010 a memorandum of understanding was signed to create a formal agreement for student-driven collaborations between UMD and NCI. Losert, Levens, and McNally became co-directors of the partnership. In 2012, Dr. Dan Larson at CCR replaced Levens as co-director, and Parent officially joined the leadership team shortly after to replace McNally. Since then, Losert, Parent, and Larson have overseen the growth of the program, from the first few students to more than a dozen now.

“You really need to have a critical mass,” Parent says. “With a few students and principal investigators, it works but it’s really small. With more students and principal investigators, like we have now, it’s more like a graduate program than ever before, and you can start to have activities such as monthly seminars and the annual symposium. Other NIH institutes and the University of Maryland School of Medicine in Baltimore are getting interested now. I’m happy, but not surprised. If you have a question and only one way to look at it, you really need to have these different types of input to really get at the answer.”

Since 2010, the UMD-NCI Partnership for Integrative Cancer Research has awarded 19 two-year seed grants to students from nine graduate programs. UMD graduate students are jointly mentored by a UMD faculty member and an NCI investigator. Thirty-four publications and several grants have resulted from these collaborations so far, and five students have graduated and obtained postdoctoral fellowships, faculty positions, and industry jobs. Although the Partnership originally started as a direct collaboration between UMD and NCI, currently six UMD students also work with other NIH institutes under this partnership.

“Aperture matters”

The UMD-NCI Partnership hosted its sixth annual symposium in February on UMD’s College Park campus, located just 13 miles from the NIH Bethesda campus. Against the backdrop of a soaring atrium encircled by sleek staircases of glass and steel in the Jeong H. Kim Engineering Building, the symposium served as a forum to report on the progress of existing collaborations and to foster new interactions between NIH and UMD investigators.

This year, the symposium celebrated the renewal of the UMD-NCI partnership for another five-year term. Dr. Glenn Merlino, CCR’s Scientific Director for Basic Research, offered his congratulations and support. “This program really epitomizes something I’ve always thought: the absolute best and most creative science comes from the junction of different disciplines, and this program nicely illustrates that,” Merlino says. “We are heavily indebted to Dan Larson and Carole Parent of CCR and Wolfgang Losert of UMD. I am here to witness this wonderful yearly event, to hear some of the great science going on, and to tell you that the CCR is very high on this partnership, and we have every intention of continuing to support the talented students associated with it.”

Dr. Patrick O’Shea, UMD’s Vice President and Chief Research Officer, also commended the success of the collaborations, noting that, while UMD is famous for its sports teams, “our research teams always have a winning year! The secret sauce is developing partnerships. We’re delighted to have great expertise at the University of Maryland, with tremendous capabilities in virtual reality, data science, and computational research.” And then, drawing on his background in astrophysics, he reiterated Parent’s point of achieving synergy, “Research is like an astronomical telescope: aperture matters. The optimum way is to take smaller telescopes and align them in a complimentary way. That’s exactly what we have in this partnership.”

Flexible research arrangements for graduate students

The UMD-NCI collaborations offer flexible arrangements for students to divide their time between the two campuses. Two of the symposium’s student speakers—Bharath Ramaswamy, a fifth-year bioengineering Ph.D. student, and Dana-Adriana Botesteanu, a fourth-year Ph.D. student in the Applied Mathematics & Statistics, and Scientific Computation Program—collaborate with clinical researchers at the NCI while spending the majority of their time at UMD.

Ramaswamy tests the effectiveness of magnetic nanoparticles to deliver steroids that counter the effects of hearing loss that results from cisplatin-based chemotherapy. He conducts his experiments in the laboratory of Dr. Benjamin Shapiro, a professor in the Fischell Department of Bioengineering at UMD, and meets his NCI advisor, Dr. Andrea Apolo, once a month to update her on the results and obtain feedback on the experimental designs. “This opportunity gave me a chance to understand how an interdisciplinary problem can be perceived from two equally important angles: medicine and engineering,” Ramaswamy says.

In addition, Ramaswamy found that having two mentors opened up a lot more connections to industry. “This program is an ideal platform for students to learn the realities of what it takes to translate an idea from inception to clinical trials,” he says.

Botesteanu, who is advised by Mathematics Professor Dr. Doron Levy at UMD and Assistant Clinical Investigator Dr. Jung-Min Lee at NCI, uses mathematical modeling to study the emergence and frequency of secondary BRCA mutations in ovarian cancer cases that were initially BRCA-deficient at diagnosis. “It truly feels like having a set of ‘academic parents’ involved in nurturing a fledgling junior scientist,” she says. “Because my research doesn’t involve ‘being under the hood’ on a daily basis, I spend about four days a week in my office at UMD and come to NIH for Dr. Lee’s lab meetings or individual meetings. I take mental notes regarding how I could better myself as a researcher by looking at their examples and career trajectories.”

Other Partnership students who spend more of their time at the NIH include fifth-year bioengineering Ph.D. student Susan Hamilla, who utilizes the NCI light microscopy core to measure the effect of contractility and substrate stiffness on the localization of RNA at cellular protrusions.

Song Chen, a second-year biophysics Ph.D. student advised by Parent and Losert, also carries out the majority of his experiments at NCI because of the cell lines he uses. Chen had a specific interest in cell migration and completed a research rotation with Losert in his first year of the biophysics program. The experience naturally led to a rotation in Parent’s lab, where she was expanding her study of cell migration to cancer. Chen continues this project, now funded by the UMD-NCI Partnership, to study the effects of surface topography on migration behavior and how it varies as the cancer cells become increasingly metastatic.

The “secret sauce” for collaboration success

What are the challenges of having a student-driven collaboration with the NIH IRP? And what makes it truly successful? Current partnership mentors Dr. Garyk Papoian, director of the UMD Chemical Physics Graduate Program, and Dr. Yamini Dalal, head of CCR’s Chromatin Structure and Epigenetic Mechanisms Group, offered their thoughts.

Papoian and Dalal jointly mentored fourth-year biophysics Ph.D. student Haiqing Zhao on a project to model the behavior of histone structures that are mis-regulated in cancer. “The culture and expectations vary at different institutions,” Papoian says, “hence, there was a learning period where we had to adjust and try to find common ground.” To be successful in a student-driven interdisciplinary collaboration, Papoian advises principal investigators (PIs) to be ready to learn each other’s languages and approaches to science and understand that a graduate student may require more mentoring than a postdoctoral fellow, the more typical laboratory member at the NIH.

As a result of their collaboration, Papoian, Dalal, and Zhao published a paper in Scientific Reports last fall and currently have another manuscript under review. Zhao presented his research at several local and national meetings and says the advantages of having two mentors greatly outweigh any challenges. Although it is sometimes difficult to find a common meeting time between two PIs, he says the experience greatly strengthens a student’s organization and communication skills. “If both PIs are busy and you don’t supervise yourself well, it is easy to get lost,” Zhao says. “Have a clear plan about the time you spend [at each institution] and what is needed. You need to keep the two advisors updated and let them know where you are in your research.”

There is also a benefit of learning from two mentoring styles and experts in two different fields. Zhao believes students from quantitative backgrounds in chemistry, physics, and math can have successful collaborations with the NIH. What is really needed, he says, is ambition and interest in biological study. “Through this program, we have a good advantage to bridge to cancer or neuroscience problems. Why not give it a try? The NIH is such an amazing resource for you to learn from. I was asking questions every moment I was there. Everyone there is an excellent researcher and you learn so much.”

A new partnership with NINDS

This year’s UMD-NCI symposium featured an exciting announcement. Beginning this year, the National Institute of Neurological Disorders and Stroke (NINDS) will fund two additional UMD students who are interested in neuroscience research.

“Like cancer, the brain is a huge mountain of questions in biology,” said Dr. Joseph Mindell, deputy director for NINDS Intramural Research. “It is a place where integrating quantitative science and biology is going to be ever more critical as we go forward. It is vital we train young people in these areas. I want to reiterate the amazing work that Carole, Wolfgang, and Dan have done to make this come together. They’ve started something great, and we’re really delighted to be included.”

NINDS investigators interested in finding UMD collaborators presented at the symposium. One of the NINDS speakers was Dr. Lucy Forrest, who uses computational approaches to study membrane proteins. “Joe [Mindell] and I have been talking about how it is difficult to have access to more quantitative students within the NIH,” Forrest says. “We have this amazing resource with UMD in close proximity, and it seems a shame not to have that connection. My lab was previously in Frankfurt, Germany, and we had a university next door with a chemistry and physics department, and a bioinformatics group. I had four students from those programs, and I think it was an extremely successful model.”

The UMD-NCI symposium highlighted how graduate student-driven collaborations with the NIH can lead to scientific discoveries, while allowing flexibility for students to craft a unique educational program.

“This has been a wonderful experience for me personally and for my laboratory,” Papoian says. “We learned an incredible amount of biology from Dr. Dalal and her group, helping us to pursue highly problem-oriented computational research. I hope other groups will continue taking advantage of the opportunities afforded by the UMD-NCI Partnership, solving together tough scientific problems using modern interdisciplinary partnerships.”

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