Three Key Questions for Breaking Into Translational Research

Breakthroughs in basic science build the foundation for clinical research and our treatment of children’s health. Many basic scientists, however, find themselves wanting to play a more active role in connecting their lab discoveries from the bench to the bedside. The Office of Postdoctoral Affairs at Children’s Hospital of Philadelphia held a Q&A panel, “How to Break Into Translational Research As a Basic Scientist,” in October as part of their week-long, biannual Translational Research Workshop.

Three experts from CHOP and the University of Pennsylvania fielded questions from an audience of basic scientists about ways in which they can get involved with the world of clinical care. A few key themes emerged, including the importance of building close collaborations with clinicians, connecting with patient advocacy foundations, and writing grants with an eye for the clinical impact of a research project. Nancy Spinner, PhD, chief of the Division of Genomic Diagnostics at CHOP, moderated the session, and panelists included:

• Michael B. Robinson, PhD, a researcher in the division of Developmental and Behavioral Pediatrics at CHOP, whose research interests include the cell biology that underpins acute brain injury
• Maja Bucan, PhD, professor of Genetics at the University of Pennsylvania’s Perelman School of Medicine, who investigates the genetic basis of behavioral and psychiatric disorders
• Nancy Bonini, PhD, professor of Cell and Developmental Biology in the department of Neuroscience at the Perelman School of Medicine, who uses Drosophila genetics to study human neurodegenerative disease.

How do you get into research into humans? What is the first step?

Dr. Robinson: I would reach out to physicians until you find one who is interested in the research problem and go from there: Start working with them, teach them about your research, and bring it back and forth. There are a lot of physicians who are interested in research but don’t have the tools that you [as basic scientists] do. One researcher, for example, was interested in stress. A urologist approached her, they started talking about the implications of stress and bladder function, and now they basically have a great collaboration.

Dr. Bucan: The entry into human genetics used to be extremely difficult; you had to have direct collaboration with a clinician who had samples, and each clinician used to have only a small number of samples. But this has changed a lot: In the mid-1990s, many different foundations interacted with each other and realized that having a big collection of samples that everybody could access is absolutely critical and the most efficient way to support collaborative research. This is basically what changed the field of autism, since many people with bright ideas who knew how to analyze data in a novel and creative way were able to obtain samples.

Having close interactions with clinicians is still absolutely critical because clinicians can describe aspects of the disease that are not captured in databases. At the same time, clinicians are incredibly busy and have a heavy clinical load. So, we have to approach collaboration keeping this in mind. We — basic scientists — have more time dedicated to research and need to be prepared to contribute a little more to grant writing, preparation of papers, literature searches.

Dr. Bonini: I want to underscore what Dr. Bucan said. Nowadays, there’s a lot more access to samples than there was; there are brain banks all over the place. You often have to have an idea that has to go through a review, and it can be really helpful to have a clinician-collaborator who can explain the complexities, if you’re coming from outside the field. These are always helpful. But now there’s a lot more ability if you have an idea to just go test it, whereas before it was completely under someone else’s control. So you can take those steps to put all those things into place. Maybe the first potential clinician collaborator you reach out to isn’t going to be the right fit, but just keep at it.

Dr. Spinner: And another part of the answer depends on the location and type of research position that you accept. Hospitals and medical schools have a wider range of jobs than basic science departments in a university setting. Classically, openings for tenure track scientists in university departments (such as the position that Dr. Bonini has) are highly competitive, with limited available positions, and hiring decisions include a variety of factors including your track record and often the type of research that you do (model organism, human cell models, computational), whereas there may be more flexibility in well-funded medical institutions. In some cases, you may be recruited to work on a clinical problem because of the basic science expertise that you bring.

On a day-to-day level, how much time do you spend interacting with patients and doctors?

Dr. Bucan: I am not a physician, so I’m not interacting with patients daily, but even in the 1990s when I was in my own lab doing mouse genetics, I was very involved in the work of different disease foundations. I was invited to advise on the board of an autism foundation and a Tourette foundation, and through work with these organizations, I was regularly interacting with patients who were very interested in advocacy. Also, today, through the Center of Autism Research at CHOP, we participate in autism walks, etc. We have plenty of opportunities to interact with the community.

Dr. Bonini: I don’t interact with patients, but in my collaborations, they have biweekly groups that focus on different pedigrees and analysis of tissues. So, I’m dealing with degenerative disease, trying to clone genes, understand the pathology, and what could be happening there. Fly genetics tell us what can be a modifier, while human genetics tell us what is a modifier. So, that’s one way we can say these are the genes in a fly, do any of these come out when you screen a human?

Dr. Spinner: I interact with patient samples on a daily basis and speak regularly to clinicians who are looking for either research or clinical results. I have frequent contact with patients through the three patient advocacy groups I work with. For example, I’ve been going to Alagille syndrome family meetings since1995 and have gotten to know a number of families extremely well. This summer, one of my colleagues and I went to a family meeting for the Ring Chromosome 20 Advocacy group in Liverpool. There are a lot of opportunities for these types of interactions if you are working on a human disease. Most of my clinical collaborators are extremely happy to have you come to clinic to meet the families and explain ongoing research projects, so there are lots of ways to interact with patients and their families.

How easy is it to get funds from federal or private agencies for your [basic science] research, and what is your first approach?

Dr. Bucan: I encourage you to start early. When you start your postdoc, look for opportunities to write your grants — not just from the National Institutes of Health, but also many foundations now have postdoc grants. Going back to this discussion of collaboration with clinical researchers, my advice is always to start thinking about that grant very early on. The worst thing is when somebody asks: “Do you want to collaborate with me, and my grant deadline is two weeks from now?” It’s very important to start building that relationship and go back and forth because it’s very educational. You learn from the clinician, and the clinician will learn from you. You have to take time to develop this relationship.