This competitive renewal application of my SRCS program is focused on three major health problems in the VA patient population, TBI, osteoporosis and osteoarthritis. One of our major areas of focus is on the long- term negative impact of traumatic brain injury (TBI) on bone. TBI, a signature injury of combat operations, results in a myriad of clinical complications that have devastating effects on our battlefield warriors and represents one of CRADO?s five cross-cutting clinical priorities. In our studies, we have established that repetitive mild TBI exerts a significant negative impact on the skeletal system over the long term by influencing peak bone mass and by promoting ectopic bone formation in soft tissues after injury. Our current studies are focused on elucidating the key cellular elements and the relevant systemic and local signaling pathways that impact the development of ectopic bone in response to TBI and local trauma with a goal of developing novel therapeutic strategies for prevention and treatment of heterotopic ossification in TBI patients. The population of elderly veterans continues to increase, and, therefore, issues affecting the aged have become a VA research priority. Osteoporosis and osteoarthritis (OA) are significant age-related public health problems in the Veterans as well as in the general U.S. population and pose a substantial financial burden. It is estimated that approximately one in two women and one in four men age 50 and older will break a bone due to osteoporosis. OA is known to affect over 30 million adults in the U.S. The pathogenesis of osteoporosis and OA are known to involve increased destruction of bone and cartilage, not compensated by parallel increases in the synthesis of new tissue. Therefore, the long-term goals of my VA- and NIH-sponsored research is focused on identifying the defective signaling pathways that contribute to bone and cartilage loss in the elderly, and to develop novel anabolic strategies for treatment of these debilitating bone diseases. Our laboratory has been very productive over the years with 370 peer review research articles, 30 review articles and 28 book chapters. Our publications have received more than 45,000 citations with an H-factor of 89 and an i-10-index of 839. Our research has led to several important discoveries in the areas of bone and mineral metabolism and has received continuous funding from federal agencies (VA, NIH, DOD) over a span of 30 years. I was the recipient of the 2017 ASBMR Louis Avioli Founder?s award given in recognition of life-long contributions in translational research related to bone and mineral metabolism. Besides establishing strong active collaborations both locally and nationally, our program continues to successfully mentor a new generation of researchers and contributes to VA research administration at both a local and national level. Our ongoing studies are designed to not only provide mechanistic insights into the role of the key signaling pathways in the pathophysiology of the various bone-wasting diseases but also to identify novel and rational drug targets for the development of novel effective therapies to treat metabolic bone diseases that impact the health of veterans.
One of the major complications of traumatic brain injury (TBI), a signature combat injury in Veterans, is heterotopic ossification (HO) that adversely affects the quality of life. Our ongoing translational research focused on identifying mechanisms and signaling molecules for TBI effects on HO will lead to the future development of effective rehabilitation strategies to minimize the adverse effects of TBI on HO and improve the general well- being of TBI patients in the VA and in the general population. Our other VA and NIH funded studies utilize state- of-the-art approaches to identify the cellular and molecular events that contribute to the pathogenesis of osteoarthritis and osteoporosis, two common musculoskeletal diseases affecting the Veterans. The goal of our research program is to identify and solve research questions that will ultimately lead to identification of novel therapeutic approaches to prevent and treat these bone diseases in the Veteran and general population.
