The Year in Review: Celebrating Our Achievements – McKnight Brain Institute!
Evelyn F. & William L. McKnight Brain Institute
Director: Todd Golde, M.D., Ph.D.
The Evelyn F. and William L. McKnight Brain Institute of the University of Florida initiated a new era with the appointment of Todd Golde, M.D., Ph.D., as executive director effective Dec. 1, 2016. Dr. Golde, a professor of neuroscience in the UF College of Medicine, established and was the inaugural director of the Center for Translational Research in Neurodegenerative Disease at UF. Steven T. DeKosky, M.D., who served as interim director of the MBI for the majority of 2016, will remain active in the MBI as deputy director. Both Drs. Golde and DeKosky look forward to working closely with the multiple neuroscience and neuromedicine research communities at UF. Gathering input from the numerous stakeholders on the UF campus during the coming year, they will develop a strategic plan for the Brain Institute that they hope will further enhance and build upon the impact and visibility of neuroscience research conducted at UF.
Neuroscience and neuromedicine research continue to flourish and expand at UF. The current NIH portfolio of neuroscience grants exceeds $35 million a year, with more than 100 NIH-funded grants along with numerous state of Florida and private foundation grants. Both the departments of neuroscience (2016 ranking, No. 12) and neurosurgery (2016 ranking, No. 15) are among the top-ranked UF College of Medicine departments in the NIH rankings from the Blue Ridge Institute for Medical Research. Although research is only one of the many factors that influence the national rankings, the growth of our neuroscience research supports both the visibility and perception of our clinical programs. Notably, in 2016 UF Health neuromedicine climbed 19 spots from the prior year to rank No. 21 in the country in the U.S. News & World Report rankings — making it one of the top two neuromedicine programs in the Southeast.
With an influx of new faculty in the neurosciences over the last five years, in part due to the UF preeminence initiative, a number of studies have coalesced that have resulted in major programmatic NIH funding. The 1Florida Alzheimer’s Disease Research Center, or ADRC, a P50 grant funded by the National Institute on Aging, is now in its second year of funding. It is one of only 30 NIH-funded ADRCs in the country; its unique focus on cognitive impairment in the elderly Hispanic population distinguishes it from the focus of the other ADRCs. Directed by Dr. Golde, the 1Florida ADRC represents a unique partnership with Mount Sinai Medical Center in Miami Beach, the University of Miami, Florida Atlantic University, and Florida International University and is the only federally funded ADRC in Florida. Serving as a hub for collaborative Alzheimer’s disease research, the 1Florida ADRC is already spurring exciting new research at UF and the other participating institutions.
Laura Ranum, Ph.D., who directs UF’s Center for NeuroGenetics, leads an NIH/NINDS (National Institute of Neurological Disorders and Stroke) Program Project Grant (P01) focusing on the central nervous system effects of myotonic dystrophy and molecular mechanisms underlying that disabling disease, which affects both neuromuscular function and cognition. These studies extend pioneering work led by Dr. Ranum demonstrating that microsatellite DNA repeats can be translated into peptides. This translation occurs despite the fact that these DNA repeats lack the canonical (required) signals for translation of proteins. Indeed, in part for recognition of this remarkable discovery, Dr. Ranum was appointed a fellow of the American Academy of Arts and Sciences, one of the highest honors in American sciences. Dr. Ranum and colleagues have also developed a novel mouse model of amyotrophic lateral sclerosis, or ALS, caused by a microsatellite repeat expansion in the C9orf gene, the most common of the several genes that cause ALS. This model is now being used to test novel therapeutic approaches to this form of ALS.
Dawn Bowers, Ph.D., of the College of Public Health and Health Professions, and David Vaillancourt, Ph.D., of the College of Health and Human Performance, co-lead an NIH-training grant (T32) on interdisciplinary training in movement disorders and neurorestoration. This training grant demonstrates the truly interactive nature of neuroscience research and training at UF as well as how focused translation research efforts can lead to the development of world-class programs. Students from engineering, neuroscience, applied physiology, rehabilitation and clinical and health psychology are being supported by the grant. The T32 involves more than a dozen faculty from multiple colleges and departments at UF. Indeed, the T32 leverages longstanding excellence in the Center for Movement Disorders and Neurorestoration led by Michael Okun, M.D., chair of the department of neurology, and Kelly Foote, M.D., a professor of neurosurgery. Their pioneering work in deep brain stimulation surgery was highlighted recently by National Geographic magazine. The T32 helps to solidify UF’s reputation as a leading institution for research on movement disorders.
Most recently, UF received a large multi-principal investigator NIH research (R01) grant. This five-year, $5.7 million grant, titled Augmenting Clinical Training in Older Adults: The “ACT Study,” is led by Adam Woods, Ph.D., Michael Marsiske, Ph.D., and Ronald Cohen, Ph.D., all now in the department of clinical and health psychology at UF’s College of Public Health and Health Professions and department of aging and geriatric research in the College of Medicine. Cohen and Woods are director and assistant director, respectively, of the Cognitive Aging and Memory Clinical Translational Research Program, or CAM-CTRP, one of two major programs supported by the McKnight Brain Research Foundation. This new translational grant aims to test the efficacy of a combination of methods designed to slow the process of age-associated memory loss — a major focus of the MBRF and CAM-CTRP — and potentially prevent onset of cognitive decline and dementia. The study will test how harmless low-voltage transcranial direct current stimulation, a form of noninvasive brain stimulation, can be combined with cognitive training to slow cognitive decline in the elderly. The ACT study can be attributed in large part to the ongoing support of UF and the MBI by the MBRF. The MBRF was established by Evelyn F. McKnight in 1999 and is responsible for the gift that named the McKnight Brain Institute of the University of Florida. In establishing the MBRF, it was Mrs. McKnight’s intent that it would support scientific research on the understanding and alleviation of age-related memory loss. Notably, the MBRF provides direct and ongoing support for both the UF CAM-CTRP program and the age-related memory loss program, which conducts studies in memory biology and behavior in animal models and translation.
The newly formed Center for Respiratory Research and Rehabilitation, housed in the MBI and led by Gordon Mitchell, Ph.D., a preeminence hire and a professor of physical therapy and neuroscience, had a very successful year. The CRRR submitted an institutional training grant application to the National Heart, Lung and Blood Institute to support the BREATHE Training Program (Breathing Research and Therapeutics). This application involves 62 trainers and collaborators from the academic health center, engineering and the applied physiology and kinesiology department. The grant received a score in the fundable range and, if not funded, this council will likely be funded upon resubmission. Members of the CRRR have been awarded a SPARC (Stimulating Peripheral Activity to Relieve Conditions) grant from the NIH Director’s Common Fund titled: “Functional mapping of peripheral and central circuits for airway protection and breathing.” This grant, led by Don Bolser, Ph.D., a professor in the College of Veterinary Medicine, provides $2.65 million in total annual costs. Multiple MBI investigators are essential to the conduct of this grant (Drs. Mitchell, David Fuller, Ph.D., Elisa Gonzalez-Rothi, D.P.T., Ph.D., and Ronald Mandel, Ph.D.). Additional new recruits to UF participating in the CRRR include Erica Levitt, Ph.D., (pharmacology and therapeutics), Russ Hepple, Ph.D., (physical therapy) and Tanja Taivassalo, Ph.D., (physiology and functional genomics). The CRRR is a great example of how the MBI is not just about a building but about supporting programmatic activities that have campuswide reach.
These large programmatic grants speak to our successful efforts to build and support translational, thematic, team science within the MBI. However, the foundation of our neuroscience research activities remains the individual investigator-based awards — R01s, R21s, private foundations and state grants. One of the major hallmarks of success in building programmatic areas of research is to ensure that we not only attract and retain preeminent scientists, such as Gordon Mitchell (PHHP) and Carol Mathews, M.D., (COM, psychiatry), but also support the careers of the next generation of investigators. The success of our junior investigators and trainees over the last year in numerous programs and departments has been outstanding, and demonstrates how investment in programmatic activities can establish the MBI and affiliated departments and programs. Our success here is reflected in the granting of T32 NIH training awards. Examples of our junior faculty and trainee successes follow.
Led by Duane Mitchell, M.D., Ph.D., a professor of neurosurgery, the Brain Tumor Immunotherapy Program is funded in large part by the Lillian S. Wells Foundation and by matching funds from UF and the MBI. The BTIP is an outstanding example of how programmatic investment can provide great opportunities for new investigators to thrive. Dr. Mitchell was the first recruit to the program and has quickly established himself as a national leader in brain tumor immunotherapy. David Tran, M.D., Ph.D., Maryam Rahman, M.D., and Elias Sayour, M.D., Ph.D., recently appointed junior faculty in the department of neurosurgery, all have received NIH faculty career development (K) awards. Notably, all of their funded work is highly translational, and demonstrates the growing integration of our basic and clinical neuro-oncology research efforts. The success of the program and anticipated future growth will be an important part of the future efforts of the UF Cancer Center to obtain National Cancer Institute designation as a nationally designated (and quality) cancer center.
Another example of programmatic efforts enabling our young investigators is the aforementioned Age-Related Memory Loss Program. This program is led by Tom Foster, Ph.D., a professor of neuroscience, and like the CAM-CTRP has ongoing support from the MBRF. This program supports multiple investigators in preclinical studies of age-related memory loss. In 2016, Sara Burke, Ph.D., an assistant professor in the department of neuroscience, received three new R01 awards studying varying aspects of cognitive aging. Dr. Burke was also the recipient of an American Psychological Association Distinguished Scientific Contributions Award. Andrew Maurer, Ph.D., another recently appointed assistant professor in the department of neuroscience, also received his first R01 and has a second R01 scored in the range that it is almost certain to be funded. We are delighted by the success of our young MBRF-supported faculty.
A third example of programmatic efforts benefiting junior scientists comes from the Center for Translational Research in Neurodegenerative Disease. This center, established by Dr. Golde and now led by David Borchelt, Ph.D., a professor of neuroscience, focuses on understanding and finding new therapeutic approaches for neurodegenerative disorders such as Alzheimer’s, Parkinson’s disease, ALS and rare disorders that are thought collectively to be caused by excessive accumulation of different proteins in the brain. One of our recent M.D.-Ph.D. trainees, Amanda Sacino, was accepted into the neurosurgery residency program at The Johns Hopkins University, one of the top training programs in the country. Working in the laboratory of Benoit Giasson, Ph.D., a professor of neuroscience, Dr. Sacino published 10 manuscripts, including eight first-author manuscripts, during her graduate and medical training. Most of these studies centered on how pathology spreads in Parkinson’s disease, and these articles are having a significant impact on the field, having been collectively cited almost 300 times in the less than three years since they have been published. Dr. Sacino’s success in our neuroscience training program highlights not only how our junior faculty but also our trainees benefit by working in a translational research environment.
Numerous scientific advances have also emerged in the MBI programs. A number of these are highlighted in the Neuromedicine 2016 Progress Report (https://indd.adobe.com/view/12a0fdf8-db65-4bb5-a26f-9ba404bf46e1). Multiple neuroscience investigators (Drs. Adam Woods, Sara Burke, Brian Hoh, Edgardo Rodriguez, Mavis Agbandje-McKenna, Habibeh Khoshbouei and Eric Wang) have been featured in the UF Research Landscape videos, which can be found at http://med.ufl.edu/research/video-spotlights/. The report and these videos show snapshots of our diverse and growing neuroscience research portfolio. Over the next year the MBI will work with our stakeholders to create additional forums for highlighting our research advances. Indeed, the breadth of our neuroscience research at UF is impressive and we need novel and efficient ways to communicate our advances both internally and externally.
A number of new clinical investigators have been hired who will support translational neuroscience research efforts as well as the larger clinical mission that will be necessary to support the opening of the new UF Health Neuromedicine Hospital this December. Dr. Sri Gururangan, FRCP, was recruited from Duke University to lead the pediatric neuro-oncology program. Dr. Michael Jaffee, M.D., an associate professor of neurology and a 21-year veteran of the U.S. Air Force, brings experience from having served as national director of the Defense and Veterans Brain Injury Center and a wartime tour as chief of the medical staff at the main U.S. theater hospital in Iraq. An expert in traumatic brain injury, Dr. Jaffee was recruited to establish a multidisciplinary brain trauma clinic associated with our memory disorders and movement disorders clinics. Dr. Katharina Busl, M.D., now chief of UF neurocritical care, is a fellowship-trained neurointensivist from Harvard/Massachusetts General Hospital. She has appointments in neurology, neurosurgery, anesthesiology and bioengineering.
We continue to update the MBI facilities and resources. The MBI’s Advanced Magnetic Resonance Imaging and Spectroscopy facility, part of the National High Magnetic Field Lab funded by the National Science Foundation, expanded both their human imaging capabilities and their support of preclinical research programs through instrument additions this year. A 3T Siemens Prisma scanner was installed in December 2016 to support a rapidly increasing number of federally funded UF investigators who are studying Parkinson’s disease, muscular dystrophy, aging and cognition, Alzheimer’s disease, adolescent brain cognitive development, traumatic brain injury and more. The Prisma has the strongest gradients available for human imaging, advanced motion correction algorithms and increased flexibility in scanning disparate areas (i.e., head to foot without having to change coils or having the subject get up and turn around). A new Bruker Advance console was installed in August to support preclinical applications at 11.1 T. It offers phased array imaging at micron resolution as well as in vivo spectroscopy methods for monitoring metabolites via 1H, 31P and 13C-DNP methods.
The addition of the 3T scanner is essential for new translational research activities at UF. For example, Sara Jo Nixon, Ph.D., a professor of psychiatry, and Linda B. Cottler, Ph.D., M.P.H., chair of epidemiology, are part of the landmark Adolescent Brain Cognitive Development (http://www.abcdstudy.org/) study, and will study 400 adolescents from the North Central Florida region who will be scanned using this machine. UF is one of 21 research sites across the country following 10,000 children ages 9 and 10 year in a 10-year longitudinal study, the first of its kind to examine brain development and child health using advanced neuroimaging and bioassays in combination with assessments of cognition, environments, substance use and social function.
Overall, the AMRIS facility, led by Joanna Long, Ph.D., supports more than 60 grants and 10 clinical trials.
Due in large part to efforts of Dr. Habibeh Khoshbouei, Ph.D., Pharm.D., an associate professor of neuroscience, who was principal investigator on an NIH shared instrument grant, we have a Nikon multiphoton Super-Resolution Imaging System available in the Cell and Tissue Analysis Core in the MBI for all researchers. An example of an image obtained from this type of microscope is shown below. Instrumentation grants, like training grants, are large and complex endeavors, and typically provide only a minor return to the PI, but are invaluable for the institution and its researchers. We are extremely grateful to Drs. Khoshbouei, Bowers and Vaillancourt and all the investigators who helped with the submission of these successful grants and other T32 and instrument grants that hopefully will be funded in the future, for their efforts on behalf of UF and the MBI. Looking forward, we will continue to assess our equipment needs to ensure that our scientists are supported with cutting-edge instrumentation.
The MBI also launched the MBI Neuromedicine Scholars program with Dr. Hank Paulson from the University of Michigan as our first Neuromedicine Scholar. This program was designed to support visits from eminent neuroscientists and opportunities not only for a seminar presentation but also for less formal interactions with trainees to provide both career and scientific advice. Further, it was designed to publicize our neuromedicine research programs. We think that this was a success, as Dr. Paulson’s parting words were, “Thanks for inviting me. This was great. I had no idea how strong the neuroscience research environment was here at UF.” We hope that with more activities like the Neuromedicine Scholars Program, we will continue to get the word out: neuroscience and MBI-supported programs are thriving at UF and we all should collectively be proud of our accomplishments in 2016.