PROVIDENCE – In July, Brown University neuroscientist John Donoghue, the director of the Brown Institute for Brain Science, or BIBS, announced that he was taking a year’s sabbatical to serve as the director of the new research center at Campus Biotech in Geneva, Switzerland.

Donoghue will serve as the center’s first director, helping to launch the Wyss Center for Bio- and Neuro-Engineering, which will provide research platforms and innovative funding to translate technology to new medical devices.

In that capacity, he will serve as an adjunct professor of the Ecole Polytechnique Federale de Lausanne, or EPFL, whose president is Patrick Aebischer, a neuroscientist who worked at Brown from 1984 through 1992, and was a founder of Cyto Therapeutics.

In his stead, Brown has appointed Diane Lipscombe, a professor of Neuroscience, to serve as Interim Director of BIBS, beginning in January of 2015.

Lipscombe’s principal research has focused on calcium ion channels in the nervous system, with a strong interest in potential drug targets in the treatment of neurological and psychiatric disorders.

Lipscombe currently serves as co-director of the Center for the Neurobiology of Cells and Circuits at BIBS, with Justin Fallon, a professor of Neuroscience. The mission of the new center, which was created in May of 2014, is to support research on neural function in health and disease at the level of cells, synapses, and circuits, working with a group of Brown faculty in basic and clinical neuroscience.

For example, the Center will facilitate and support research focused on understanding the mechanisms underlying such diseases and disorders as autism spectrum disorders, neurodegenerative disorders including amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s Disease), and chronic pain, including the migraine disorders. 

[In the ALS Ice Bucket Challenge featuring Brown University President Christina Paxson, Lipscombe administers the bucket of icy water. See link to ConvergenceRI article below.]

Lipscombe and three of her colleagues at BIBS – Julie Kauer, Christopher Moore and Carl Saab – recently received a $300,000 award to study the physiology and mechanisms of migraines from the Association for Migraine Disorders. The research will focus on identifying the cells and circuits that cause migraines and possible opportunities for creating therapies.

Lipscombe described the integrative research project that would examine migraine at the behavioral, circuit, cellular and molecular level as reflective of the mission at BIBS: “To facilitate collaborative research aimed at understanding basic and disease mechanisms of the brain.”

ConvergenceRI spoke with Lipscombe recently about the challenges involved in undertaking the interim directorship at BIBS.

ConvergenceRI: What are the immediate challenges? Does it increase demands on your time? Will it mean less time in the lab?
LIPSCOMBE: In terms of my calendar and adding things, I will be juggling things around.

In November I rotate off as chair of the Scientific Publications Committee for the Society for Neuroscience. My classroom teaching load is lighter, come January, when I assume the interim directorship. I’ll continue to run my lab, and will continue to manage current research projects as well as develop new lines of research.

NIH funding for my laboratory was just renewed for five years through 2019. But I’m always teaching; I have had undergraduates working in the lab as part of my research team since arriving at Brown in 1990, as well as a superb team of graduate students and postdoctoral associates.

I really like the work that I’m doing. I’ll be learning a lot and looking forward to that. 

I’ll have to be more efficient about priorities. One of the activities I’m looking forward to is to explain to lots of different groups about what the Institute does, what it does well – and where we have opportunity to continue to expand.

The greater scope of the research initiatives in BIBS that I will help to facilitate and grow are extremely appealing aspects of serving as the Interim Director.

ConvergenceRI: There have been some conversations about creating a new building for brain sciences in Providence.

LIPSCOMBE: The Institute has been very successful. The face of brain science at Brown continues to grow. There are lots of opportunities to do a lot more collaborative research activities. There’s a lot of capacity to still grown in those areas. 

Having a dedicated research facility that encourages those types of collaborative activities that wouldn’t necessarily occur otherwise would be great.

ConvergenceRI: Is Rhode Island, Providence and Brown in particular emerging as a national hub of neuroscience research?
LIPSCOMBE: Without question, neuroscience at Brown is nationally recognized. I think, for sure, the group of faculty – individuals and collectively, have been recognized as being some the leading scientists in the county and globally.

ConvergenceRI: How has the new federal NIH initiative on brain research by the Obama administration been playing out?
LIPSCOMBE: I’m pretty sure that John [Donoghue] will remain on the advisory committee to the NIH director. The first round of BRAIN (Brain Research through Advancing Innovative Neurotechnologies) grants have just been awarded. One of our colleagues was part of a collaborative team that was awarded funding.

Given the strong track record in innovation in the area of neurotechnologies, BIBS faculty are likely to be successful in competing for this support.

As exciting as the BRAIN initiative is, overall federal funding for biomedical research remains far below what is needed to maintain our global competitiveness. This is one of our greatest challenges as neuroscientists.

Time and time again, great discoveries are made in the most unexpected areas. Collectively, we have an amazing capacity to take advantage of new technologies to understand brain function, but we are not good at knowing where the next great discovery will come from.

It is crucial to support the very best basic research, including studies of model organisms such as the fruit fly and a range of disciplines such as neuroscience, engineering, applied mathematics, and genetics.

ConvergenceRI: What kind of impact has National Institute of Mental Health Director Thomas Insel’s efforts to change the research focus – incorporating genetics, imaging and cognitive science to transform the diagnosis of mental disorders – on brain research?

LIPSCOMBE [laughing]: Tom Insel directs the $1.5 billion annual research budget at NIMH; he’s fairly influential.

I think there are lots and lots of factors that are driving many people who are interested in brain science to focus on mechanistic studies of the brain.

His vision at NIMH is one of them. I think others have to do with the non-invasive tools that are now available to investigate the human brain.

What’s been a huge, huge, huge change over the last 10-15 years is the development of tools to visualize and study the activity of specific classes of neurons in the brain, to control their activity, and to address mechanistic questions of how the normal brain works, and how the diseased brain malfunctions. As well as the human genome sequencing initiative, that has transformed our ability to understand the genetic underpinnings of many diseases.

Tom’s vision, in addition to the major advances in tool development, has combined to strongly influence research.

ConvergenceRI: Is there greater emphasis on collaborative, translational research? John Donoghue’s work at the new Wyss Institute appears to be focused on translational research.
LIPSCOMBE: The more we know about the brain and how the brain works, the more likely we’ll be able to understand the basis of what happens when things don’t work well. In disease, in disorders, whether they’re hereditary, early onset, late onset.

No single approach is going to get us there, or going to advance the field in a very dramatic way.

Neuroscience is multi-disciplinary by definition; multiple approaches are absolutely required in order to take what goes on at the bench and translate that into clinical therapy and treatments – physical rehabilitation, behavioral, surgical – all of these types of clinical applications.

ConvergenceRI: What kinds of collaborative research efforts do you anticipate with the new URI neurosciences institute, with the VA, and with the Prince Neurosciences Institute?
LIPSCOMBE: First, I am looking forward to getting more fully acquainted with the status of the other initiatives in the state, including the URI neurosciences institute.

There are already successful partnerships between BIBS and the Norman Prince Neuroscience Institute, Butler Hospital, and the VA. We’re all working toward the same goal: to further our understanding of the brain and to further the diagnosis, treatment, and rehabilitation of those with brain diseases, disorders and injuries.

There is great potential for collaboration. URI is looking for a director for the Ryan Institute for Neuroscience. When there is a director in place, I expect there will be opportunities for collaborations on research as well as education and training.

ConvergenceRI: There has also been some discussion regarding the potential of the creation of an independent, private investment fund in Rhode Island that would invest in neuroscience and bio-medical startups.

LIPSCOMBE: The Institute has a fabulous record of facilitating the awarding of a number of different grants from foundations and private donors, as well as a lot of success in [receiving] awards of federal funds.

The Institute has also been involved in the piloting of new projects that traditionally are not funded by federal grants – these typically are only successful once substantial amounts of preliminary data have been gathered. The Institute has been incredibly successful in generating seed funding for these types of innovative new projects.

As a result, BIBS has proven successful by promoting and finding ways to seed funding to investigators – and facilitating research that wouldn’t happen otherwise, or wouldn't happened as quickly.

That said, having a new fund within Rhode Island that focuses on translating basic findings into tools, treatments, or pharmaceuticals would be fabulous.

Several BIBS scientists have been involved in biomedical startups, including Donoghue and Fallon. Others of us have a long history of working with pharmaceutical companies licensing materials, including my own lab. I will be meeting with a number of key individuals to find out how BIBS can assist in promoting private investment in the areas of brain science and brain health.  

ConvergenceRI: How are things progressing in the efforts around BrainGate the initiative around creating a small, iPhone-like wireless device for processing interactions with the implanted chip in the brain?

LIPSCOMBE: It’s a very important part of the Institute, but I would refer you to the people who are involved in that initiative, including John Donoghue, Leigh Hochberg, and Arto Nurmikko to talk about how they are doing in terms of research. John [Donoghue] is still going to be heavily involved.

ConvergenceRI: Much of the focus of your research is on the calcium channel, as I recall from a presentation you made at the medical school in April. Is that correct?
LIPSCOMBE: Yes, I’m an expert on calcium ion channels in the nervous system, with a strong interest in potential drug targets of neurological and psychiatric disorders. My NIH funding for part of this research was just renewed for five years, so I’m very happy.

I’m involved in a number of research initiatives, including some new collaborative projects within BIBS aimed at understanding cell and circuit mechanisms of migraine disorders. Our team (myself, Kauer, Moore, and Saab) are also talking with Dr. Julie Roth, [a neurologist at Rhode Island Hospital], who has joined our discussion group. She has great insight into patient care and how they diagnose migraines. It’s a spectrum of disorders, not a single disorder. 

I expect these kinds of multi-disciplinary collaborations that connect discoveries at the bench to clinical applications will only increase.

Another potential area of great growth in terms of my own research is in the area of psychiatry. There are human-to-human variations in the sequences of our genes – common variants. Common variants in human genes that code for calcium ion channels appear to collectively contribute to an individual’s susceptibility to many psychiatric illnesses, including schizophrenia and bipolar disorder. I expect to build collaboration with my colleagues in psychiatry who are interested in understanding the importance of the regulation of calcium, and calcium ion channels in psychiatric disorders.