CTSA Pilot and Collaborative Studies

Dr. David Guzick, M.D., Ph.D.

July 26, 2007

A major component of the Clinical and translational Science Award (CTSA) at the University of Rochester School of Medicine and Dentistry is the opportunity to fund germinal studies that require data collection before a grant can be prepared form more definitive funding. In the last newsletter, we discussed the awards given to faculty who proposed novel approaches to translational methodologies. In this newsletter, I will describe awards for pilot projects under the CTSA Pilot and Collaborative Studies Program. This program also funds trainee and travel awards, which will also be described.

The overall goal of the Pilot and Collaborative Clinical and Translational Studies Program is to provide research support for preliminary and proof-of-concept studies critical to moving basic laboratory findings into clinical applications. High priorities of the program are to facilitate development of enabling technologies, new therapeutic, diagnostic, or outcomes assessment approaches, and innovative cross-disciplinary collaborative programs. Pilot funding is targeted at research proposals which demonstrate ability to be catalytic in terms of generating new programs, directions, and funding for clinically applied research and methodologies.

The Pilot Program utilizes a number of funding mechanisms to ensure flexibility in the ability to take advantage of new funding opportunities. This past month the Pilot and Collaborative Studies Program announced the Award recipients for the first round of competitive funding. Awards were distributed across three categories; Faculty, Trainee, and Travel, and the recipient names can be found below. A new RFP was released on July 9th, 2007. Please check the CTSI website for further details.

Randy Rosier, MD, PhD, and Richard Moxley, MD direct this program for the CTSI. The review procedure for choosing awardees consisted of two phases. In the first phase, brief one-page preliminary applications in abstract form were reviewed by a standing Coordinating Committee. This Committee invited a limited number of full applications from the initial set. Full applications were reviewed by ad hoc reviewers selected on the basis of their expertise. Proposals were scored by all reviewers, and the ad hoc reviewers met to discuss their scores and select awardees. One ad hoc reviewer was assigned to serve as a mentor to each investigator whose proposal was not selected.

Fifty-four preliminary applications were submitted: 38 faculty pilots, 11 trainee pilots and 5 traveling fellowships. After review by the Coordinating Committee, 10 faculty proposals, 7 trainee proposals and 4 travel award proposals were solicited, for a total of 21 solicited proposals.

In addition to Drs. Rosier and Moxley, the Coordinating Committee consists of Drs. James Eichelberger, Kishan Pandya, Rick Waugh, Chris Ritchlin, Nancy Bennett and John Treanor. The level of commitment to this program by medical school faculty is truly extraordinary: 86 faculty members agreed to serve as ad hoc reviewers/mentors.

Here, then, is a little bit about the Pilot and Collaborative Studies projects, and about the people who received the awards:

Faculty Awards

Laura Calvi, M.D.,
Assistant Professor of Medicine
in the Division of Endocrinology

Laura Calvi, MD is an Assistant Professor of Medicine in the Division of Endocrinology. She was profiled in my newsletter dated August 26, 2005, when she was honored as a Pew Scholar. Having been raised in Italy through much of High School, Laura attended Union College and then Harvard Medical School, where she took a year out to conduct research. This experience sparked a commitment to research as a career, which extended through training in Internal Medicine and Endocrinology at Massachusetts General Hospital en route to Rochester. In addition to her Pew grant, Dr. Calvi's work has been supported by NIH K08 and K21 awards. Although to date Dr. Calvi's research has mainly used transgenic mouse models, the aim of the pilot is to define changes in the bone and bone marrow in humans that occur as a result of in vivo treatment with parathyroid hormone (PTH). Patients receiving PTH for osteoporosis will undergo prospective bone marrow sampling, with analysis of stem cell and osteoblast compartments. Collaborators include Susan Bukata, MD (Assistant Professor of Orthopaedics) and Jonathan Friedberg, MD Associate Professor of Medicine). The goal is to confirm previous findings in mouse models that PTH exerts a myeloprotective effect. If these mouse findings are found to translate to humans, there would be exciting support for the therapeutic potential of parathyroid hormone (PTH) in a variety of bone and malignant diseases, including bone marrow failure states, and iatrogenic stem cell aplasia due to chemotherapy or radiation.

Charles Duffy MD, PhD,
Professor of Neurology

Charles Duffy MD, PhD, is a tenured Professor of Neurology. He received an A.B. in Psychology and Social Relations from Harvard College and went on to the MD-PhD Program at John Hopkins Medical School, earning his PhD in physiology. After an internship at Hopkins in Medicine, he took his Neurology residency at the Massachusetts General Hospital. He was recruited to Rochester as an Assistant Professor in 1993, and rose through the ranks to appointment as Professor in 2003. He is widely recognized for his work on visual-spacial orientation and processing by the brain in normal aging and in Alzheimer's disease. This work is currently supported by two R01 grants, both of which are in years 6-10 of funding. His pilot project, entitled, "VEP's in Aging and Alzheimer's Disease," uses visual evoked potentials (VEPs) to predict a patient's ability to navigate independently based on linked neurophysicological and psychological measures. The information from this pilot and follow-on studies may substantially improve the quality of life for patients who suffer from Alzheimer's disease, which is becoming increasingly important in our aging population.

James McGrath, PhD
Associate Professor of Biomedical Engineering

James McGrath, PhD, is Associate Professor of Biomedical Engineering. After obtaining his B.S. in mechanical engineering at Arizona State University, he obtained his PhD in Biological Engineering from the Harvard/MIT program. He was recruited to the Department of Biomedical Engineering in 2001, and became Director of the Graduate Program in Biomedical Engineering in 2004. Dr. McGrath's pilot project, which includes several collaborators [Drs. Jessica Snyder (PhD candidate in Biophysics), Philippe Fauchet (Professor of Electrical Engineering), Alan Friedman (Director of Proteomics Core) and Jeremy Taylor (Nephrology)], will investigate the potential of a novel, silicon-based membrane material (silicon nanomembranes) to provide improvements in hemodialysis that are described as "revolutionary." These membranes are four orders of magnitude thinner (only 15 nm thick) than synthetic and biopolymer membranes currently used in dialysis, which should lead to vastly improved molecular discrimination. This pilot study is the first effort of this group to apply these silicon nanomembranes to solve a specific biomedical problem. It would indeed be a dramatic example of translational science if these ultrathin membranes could be used to improve the lives of patients requiring hemodialysis.

Patricia J. Sime, MD
Associate Professor of Medicine and Environmental Medicine

Patricia J. Sime, MD is an Associate Professor of Medicine and Environmental Medicine. Born and raised in Scotland, she received her Bachelor's Degree and Medical Degree from the University of Edinburgh and the Royal College of Physicians. She then took her residency training in Medicine in Edinburgh, and a Fellowship in Pulmonary Medicine at McMaster University in Ontario, Canada, where she became interested in adding basic and translational science to her clinical career in pulmonary medicine. She was recruited to Rochester in 1999, received a K08 Award in 2001 and an R01 in 2005 on the molecular mechanisms that explain lung scarring. In this project, Dr. Sime takes advantage of her recent identification of aryl hydrocarbon receptor (AhR) as a previously unrecognized down-regulator of cigarette smoke-mediated inflammatory disease in mice. In the pilot, she and her collaborators (Sanjay Maggirwar, PhD (Assistant Professor of Microbiology & Immunology), Thomas Gasiewicz, PhD (Chair of Environmental Medicine), Michael Larj, MD (Assistant Professor of Medicine), and Richard P. Phipps, PhD (Professor of Environmental Medicine) will attempt to translate their animal model studies to humans by investigating lung tissue, fluid and cells from smokers with and without disease. They will test the hypothesis that activation of AhR dampens human cigarette smoke-induced inflammation. If so, these new studies will identify the AhR as a novel target for future therapy of lung inflammation, and possibly smoking-induced cardiovascular disease.

Xinping Zhang, PhD
Assistant Professor of Orthopaedics

Xinping Zhang, PhD, is an Assistant Professor of Orthopaedics. After receiving her M.D. from Shanghai Medical University and her M.S. in Molecular Biology, Dr. Zhang came to Rochester for her PhD training, which she completed in Biochemistry. Dr. Zhang Joined the Dept. of Orthopaedics in 2000 and finished her postdoc training with Dr. Edward Schwarz in 2001. Since then she has been a faculty member in the Dept. of Orthopaedics, Center for Musculoskeletal Research. Her project also has a translational nanotechnology focus, which is one of the innovative science programs emphasized in the URMC Strategic Plan. Specifically, to treat patients with large segmental bone defects, Dr. Zhang proposes a tissue engineering strategy to fabricate a 3D cellular scaffold. Although some work on tissue engineering for the repair of bone defects has been reported, a major limitation has been the lack of a cellular osteoinductive scaffold that could fit around a bone of any size and shape. Dr. Zhang and a multidisciplinary team proposes to use 3D tissue fabrication via electrospinning as a versatile and efficient technique for the fabrication of nanofiber-based scaffolds that match the structural characteristics of extracellular matrix. Included in the team are Dr. Zhang (a bone biologist), Dr. Hong Yang (Associate Professor of Chemical Engineering, an expert in multifunction nanomaterials), Dr. Younan Xia (Professor of Chemistry, U. of Washington, an inventor and pioneer of electrospinning) and Dr. YanFang Ren, (Assistant Professor of Dentistry). Success in these studies on bone tissue engineering would hold much promise for the treatment of bone defects.

Trainee and Travel Awards

In addition to funding pilot projects proposed for faculty, the CTSA also funds trainee awards. Anitha Krishnan is a PhD candidate in Biomedical Engineering who has completed her formal coursework. Her efforts are not concentrated on research towards her PhD thesis. Her proposal addresses a critical need for improved treatment of glioblastoma, which currently has a dismal prognosis with current chemotherapy and stereotactic radiotherapy. In particular, radiation treatment is ineffective in protecting against recurrences unless it also treats local spread. However, it lacks the precision required to treat local spread without also ablating a large amount of healthy brain tissue. Anitha seeks to develop and validate predictive models of local cell dispersion using datasets from high resolution in vivo MR diffusion tensor imaging (MR-DTI). It is hoped that such knowledge will lead to prolonged survival of patients with glioblastoma by treating tumor cells that spread out from the primary cancer site, without damaging health tissue.

Finally, the Pilot and Collaborative Studies Program of the CTSA funds travel awards. This first round of travel awards were awarded to Rebekah Loy, PhD, Research Associate Professor of Neurology, and to Jennifer Gewandter, a PhD student in Biochemistry and Biophysics. Dr. Loy will be spending 3 weeks learning methodology related to epigenetic gene regulation in the laboratory of Dr. Simon D. Spivak at the Wadsworth Research Center. She will then develop techniques that will allow her to test the hypothesis that epigenetic mechanisms may contribute to psychosis and agitation in people with Alzheimer's Disease, as well as responsiveness to mood stabilizer therapy. Jennifer will be spending 4-8 weeks in the laboratory of Dr. Jenny Hinshaw at NIH. She will be focusing on the mitochondrial fission protein DLP1 (dynamin-like protein 1), which is critically involved in the severing of mitochondrial membranes that plays such an important role in mediating the pathologic effects of reactive oxygen species (ROS). In order to target DLP1 as a potential therapeutic agent for conditions caused by ROS, we must understand the mechanism of action of DLP1, which is exactly what Jennifer will be attempting to do at NIH.

The CTSI recently launched its website. Check it out! You will find information on how to apply for these awards, as well as information about what else is occurring under the CTSI umbrella.

Meliora,

David S. Guzick, MD, PhD
Dean, School of Medicine and Dentistry
University of Rochester

Dean's Newsletter

Posted May 28, 2009:
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