A Perfect 10

Now that I’ve got your attention, it’s not what you’re thinking. The title of this newsletter refers to the perfect score of 10 that is given, only rarely, by NIH study sections to grant applicants. Recently, and amazingly, three grant applications from the Department of Physical Therapy in the College of Public Health and Health Professions received a perfect 10. This newsletter will highlight faculty members of the Department of Physical Therapy, who have produced a burgeoning grant portfolio by reaching high in the pursuit of research excellence, and by taking advantage of the collaborative spirit at UF.

First, let me provide some context. The environment for submitting grant applications to NIH has become increasingly challenging. The NIH budget has remained flat at about $30 to $31 billion since 2009 (not counting stimulus money in 2009 and 2010); in constant dollars adjusted for inflation, the fiscal year 2012 budget is $4 billion lower than the peak year in fiscal year 2003, and at the lowest level since fiscal year 2001. Therefore, it is not surprising that the number of research grants funded by NIH has declined every year since 2004. For fiscal year 2011, the last year that data are available, NIH made 8,765 competing (new and renewed) awards, more than 1,600 fewer than in 2003.

In this environment, pay-lines for grants at NIH study sections have become tighter, and reviewers have become more strict in their assessments of submitted grant applications. Each reviewer is asked to assign an overall scientific “impact score” using a 9-point scale, and are guided to use the full range of the rating scale — spreading scores to discriminate among applications. A score of 1 indicates an exceptionally strong application with essentially no weaknesses. A score of 9 indicates an application with serious and substantive weaknesses and very few strengths; 5 is considered an average score.

Individual reviewer scores are averaged and the result is multiplied by 10 to determine the final impact score. Thus, the range of the final application scores is from 10 through 90. You can see how tough it is to receive a perfect 10! The grant must consistently be scored as a “1” (exceptional) by all 25 to 30 members of the study section.

Now let’s look at the recent “perfect 10” grants from the Department of Physical Therapy:

One is a K12 training grant in which the principal investigator is Krista Vandenborne, Ph.D., professor and chair of the Department of Physical Therapy. UF has a paucity of training grants, which are designed to provide the infrastructure needed to train the next generation of investigators. This grant, titled “Rehabilitation Research Career Development Program (RRCD),” is a renewal of Dr. Vandenborne’s current grant that funds the training of rehabilitation scientists who are occupational and physical therapists, and includes collaboration with other universities. Some history is of note: In 2007, a new RFA was released from the NIH for K12 consortium applications in the field of rehabilitation. The RFA noted that three grants would be awarded, one in each of the following areas: 1) rehabilitation engineering, 2) physical and occupational therapy, and 3) neurology and neurosurgery. Top physical therapy programs across the country tried to position themselves to submit a strong consortium application for the second category. UF partnered with The University of Texas Medical Branch (UTMB). Drs. Kenneth Ottenbacher (UTMB) and Vandenborne crafted a solid application as co-directors, the consortium received the top score nationally and the grant was funded. This K12 award has provided national prominence to UF’s Department of Physical Therapy, and has allowed the department to recruit outstanding junior faculty nationally.

The goal of the now-renewed RRCD Program is “to increase the number of rigorously trained, extramurally competitive and scientifically competent rehabilitation scientists who will conduct translational investigations, lead clinical research teams and eventually mentor the next generation of occupational and physical therapy investigators.” The University of Southern California, with Dr. James Gordon as site principal investigator, was added to the UF/UTMB consortium. The training program comprises two phases. Phase 1 (Years 1-3) is designed to provide the scholars with the foundation needed for a productive career in interdisciplinary rehabilitation research. Scholars will conduct research at one of the consortium institutions under the supervision of a Lead Mentor and collaborate with members of an interdisciplinary research team in their area of research interest. In Phase 1, scholars will acquire research experience, generate, analyze, present and publish research data and become equipped to compete for independent external funding. In Phase 2 (Years 4-5), scholars transition to independent researcher positions. Eighty-eight percent of scholars who transitioned to Phase 2 since 2007 have obtained individual external funding from the NIH or VA. This is an extraordinary result in the current NIH environment and is a testimony to the dedication of Dr. Vandenborne and the other faculty who serve as mentors.

A second “perfect 10” grant was recently awarded to David Fuller, Ph.D., for his new R01 application titled “Modulation of Phrenic Motoneuron Plasticity after Cervical Spinal Cord Injury.” Patients with spinal cord injury often develop difficulty breathing because of injury to nerves in the spinal cord that control respiration. The research project to be conducted by Dr. Fuller and his colleagues is based on the fact that the injured spinal cord has a robust capacity for “neuroplasticity,” which allows the nerve cells in the brain to compensate for injury and disease and to adjust in response to new situations or to changes in their environment. The goal of their research is to develop an understanding of how this neuroplasticity can be harnessed therapeutically to enhance respiratory outcomes after injury to the cervical (neck) portion of the spine. Fundamental to improved rehabilitation after spinal cord injury (SCI) is an improved understanding of the complex circuit between the spinal cord and respiration, and how the spinal respiratory nerve cells are controlled physiologically after SCI. In principle, the injured spinal cord is essentially a “new spinal cord” in which neural networks and control mechanisms affecting virtually every aspect of the system are significantly altered. Dr. Fuller and his research team will build upon their recent characterization of the spinal respiratory circuit anatomically after cervical SCI, and will now define key relationships that develop after SCI between altered anatomy and altered physiology. In this project, Dr. Fuller and his research colleagues will conduct a series of experiments in a rat model that will define the spinal respiratory circuit neurophysiologically after cervical SCI, examine the influence of a key neuromodulator – serotonin – on the circuit, and determine the impact of a promising spinal cord transplantation approach on spinal respiratory neurons and recovery of respiration after cervical SCI.

A third “perfect 10” grant is a renewal of an R01 grant titled “Control of Breathing and Pompe Disease,” in which both Dr. Fuller and Barry J. Byrne, M.D., Ph.D. (professor of pediatrics and director of the Powell Gene Therapy Center) are principal investigators. Pompe disease is a neuromuscular disorder resulting from mutations in the gene for acid alpha-glucosidase — an enzyme necessary to degrade lysosomal glycogen. Hypoventilation is a hallmark feature of Pompe disease and work from the first cycle of this grant demonstrated that neuropathology contributes to Pompe breathing problems. This is important since the current therapy for Pompe disease - intravenous enzyme replacement therapy (ERT) directed at the muscle - does not target the central nervous system (CNS). The substantial effort needed for biweekly ERT treatment at a cost of >$500K per year, as well as the potential immune responses and limited success of ERT, warrant an improved approach. The studies conducted in the renewal target optimization of adeno-associated virus-based therapies to treat the CNS in Pompe disease. (See On The Same Page “Gene Therapy,” December 14, 2011).

This innovative work on the development of new therapies for the respiratory insufficiency in Pompe disease is part of an ongoing and highly successful collaborative effort between a clinician and gene therapy researcher (Dr. Byrne) and a respiratory control scientist (Dr. Fuller). For this newsletter, I asked Dr. Fuller to comment on his research goals. He states: “First, a major goal of mine is to help bring an NIH program grant to UF that focuses on the use of diaphragm stimulation as a rehabilitation tool (vs. just a means of maintaining alvelolar ventilation). The UF Health Science Center has, in my opinion, the best concentration of cutting-edge expertise in respiratory neurobiology of any academic center in the world. The bottom line is that we have the talent and the ideas to do this. Second, my colleagues in the McKnight Brain Institute, particularly Drs. Paul Reier and Michael Lane (Department of Neuroscience) and Dr. Daniel Hoh (Department of Neurosurgery) and I, are actively planning to create a Center for Spinal Cord Injury and Repair Research. Again, we've got great talent in this area, and I think this could be a major strength for UF.”

Much of this progress in the Department of Physical Therapy in the College of Public Health and Health Professions can be traced to its chair, Krista Vandenborne, Ph.D. I first met her when I arrived in 2009, which was a watershed year for her own research program: she obtained an RC1 grant (score – 10), which has facilitated the expansion of the muscular dystrophy program at UF, a program project grant on therapeutic strategies to promote muscle recovery after spinal cord injury, and a multicenter R01 grant on imaging and biomarkers in muscular dystrophy. But this remarkable story begins earlier, and it is illuminating to consider some of the steps taken by Dr. Vandenborne to grow a small department of physical therapy into a veritable national powerhouse.

Dr. Vandenborne came to the U.S. from Belgium in 1989 as a physical therapy graduate on a Fullbright award (Belgian American Educational Foundation) to learn about MRI. She describes herself as “fortunate enough to be trained by pioneers in the field of magnetic resonance” at the University of Pennsylvania and started as a research assistant professor at Penn in the Department of Rehabilitation Medicine with joint appointments in Physiology and in Radiology. In 2001, Dr. Vandenborne was recruited to UF as an associate professor by Dr. Robert Frank, then dean of Health Professions, and Dr. Bill Luttge, then director of the McKnight Brain Institute (MBI). Her husband, Glenn Walter, was recruited as a tenure-track assistant professor in the Department of Physiology and Functional Genomics. They were both attracted by UF’s association with the National High Magnetic Field laboratory, the strength of the MBI and Dr. Luttge’s vision, as well as the strong collaborative spirit across many programs. In evaluating their options and comparing with other offers, Dr. Vandenborne explains that “the hospitality of UF and the collaborative programmatic approach sealed the deal.”

In 2002, Dr. Frank asked Dr. Vandenborne to consider becoming the chair of the physical therapy department. She recalls: “I was 36 at the time, my research was taking off, and I had only been a Research Assistant Professor until recently. Yet, somehow I felt I had the vision to lead the department forward. I could see lots of productive connections and collaborations that had been untapped and could really excel the department. In my view the department, similar to many other U.S. physical therapy departments, had been very parochial in its approach — only relying on internal resources and not recognizing what it had to offer to other groups and departments. In my view, my job would mainly consist of opening doors and making the connections. I felt comfortable in this role. In my negotiations with Dr. Frank, he charged me with making a strong academic department and building an NIH portfolio. I was able to obtain additional faculty lines, had the support of Bill Luttge for faculty start-up, and the approval to hire an assistant chair to direct the clinical physical therapy program.”

Within six weeks of accepting the role of chair, she and her faculty wrote the pre-doctoral NIH T32 training grant in Neuromuscular Plasticity and Rehabilitation. The training grant was built on the principles of integrating clinical and basic science students and faculty from different disciplines. Since, in Dr. Vandenborne’s view, the senior “muscle community” and “neuro-rehabilitation community” were too small as independent entities, she merged the groups and the theme “neuromuscular plasticity” emerged. The leadership and faculty of the training grant were recruited from across different colleges and became the core network for their efforts. To date the program is in its tenth year and has supported 22 students, organized eight symposia, and hosted more than 100 invited speakers.

Dr. Vandenborne recalls that some faculty members “were a bit worried about the fate of clinical education under a new chair with a strong research agenda.” She therefore decided to focus on education first and invited three prominent leaders in physical therapy education to evaluate the clinical physical therapy program. Their recommendations were to start a doctoral physical therapy (DPT) program, close the master’s of health science program, build a residency program and build strong relationships with Shands for clinical internships. The recommendations of the committee became the department’s blueprint for clinical education. To date, the department has graduated 261 DPT students and the program is ranked 4th in the nation for AAU public universities by U.S. News & World Report. The residency program has trained a total of 17 residents in the areas of Orthopedics, Sportsmedicine, Cancer Rehabilitation and Neuro-Rehabilitation, and, in conjunction with Shands Rehabilitation Serves, has played an important role in enhancing patient care, promoting evidence-based practice and promoting leadership in a variety of Shands clinical settings. The department also houses one of the largest Ph.D. programs in rehabilitation sciences in the country.

The next several years were a period of intense recruitment to bring strong rehabilitation scientists and national leaders to the department. Dr. Vandenborne recruited nine new faculty. Besides Dave Fuller, whose work was highlighted above, Mark Bishop PT, Ph.D., Terese Chmielweski PT, Ph.D., Jane Day, PT, Ph.D., Steven George, PT, Ph.D., Steven Kautz Ph.D., Mary Thigpen PT, Ph.D., Claudia Senesac PT, Ph.D., and Carolynn Patten, PT, Ph.D., joined the department. Many of these faculty recruitments were accomplished in collaborations with centers, such as the VA Brain Rehabilitation Research Center, the Powell Gene Therapy Center, Center for Pain Research and Behavioral Health and the MBI. Junior faculty received several successful K-awards and senior faculty obtained R01 grants. The department, which now lists 23 faculty, was on its way.

Areas of strength are neuro-rehabilitation, musculoskeletal pain and injury and cardiorespiratory training. Of special note, UF has built a strong research program in Duchenne muscular dystrophy, with projects ranging from animal models to clinical trials in patients. The program is recognized internationally and funded by a variety of different grants, including a multicenter R01 grant and a Wellstone Center grant. The collaborative network at UF includes a cadre of senior and junior investigators, including Drs. Walter (Physiology), Byrne (Pediatrics), Vandenborne (Physical Therapy), Senesac (Physical Therapy), Lott (Physical Therapy), Bendixen (Occupational Therapy), Forbes (Physical Therapy), Baligand (Physiology) and Willcocks (Physical Therapy). UF is well positioned in a consortium for muscular dystrophy research with University of Pennsylvania, Oregon Health and Science University, University of California, Los Angeles, NIH and the University of Chicago as research and clinical partners. As part of its efforts to bridge research and clinical service, the UF muscular dystrophy group started the Neuromuscular Clinic, a partnership between the departments of Pediatrics, Neurology and Physical Therapy.

Total annual research funding over the last three years in the Department of Physical Therapy has averaged $5.1 million. Faculty members have become leaders in the American Physical Therapy Association and serve as editorial board members for leading peer-reviewed journals. As of today, five faculty serve on NIH study sections, and others chair national committees, and organize national and international conference sessions. They publish extensively (>65 papers annually) and contribute to the development of the clinical practice guidelines for the physical therapy profession. Dr. George, for example, recently co-authored an important paper linking clinical practice guidelines to the International Classification of Functioning, Disability, and Health (ICF) model and setting the standard of care for Orthopaedic Physical Therapy Practice (J Orthop Sports Phys. Ther. 2012 Apr;42(4):A1-57. Epub 2012 Mar 30) In addition, Dr. Martin’s innovative respiratory training model has had a significant impact clinically, and has led to reduced length of stay in the ICU (Crit Care. 2011;15(2):R84. Epub 2011 Mar 7).

Most recently, in response to the cumulative state budget cuts, the department has developed plans to expand the Department of Physical Therapy class from 55 to 70, via a self-funded budget model. The proposal has been approved by the president and is being submitted to the physical therapy accrediting body for approval. The department is exploring an integrated laboratory classroom/clinic, which would facilitate an innovative clinical education model and add yet another dimension in which it is at the forefront of the field of physical therapy. All in all, the Department of Physical Therapy in the College of Public Health and Health Professions is an inspiring example of what can be accomplished at UF by bringing together a superb faculty and staff who leverage their talent and experience with the spirit of collaboration throughout the university. A perfect 10 indeed!

Forward Together,

David S. Guzick, M.D., Ph.D. Senior Vice President, Health Affairs President, UF&Shands Health System