Grants Funded
Grant applicants for the 2024 cycle requested a total of nearly $3 million dollars. The PSF Study Section Subcommittees of Basic & Translational Research and Clinical Research evaluated more than 100 grant applications on the following topics:
The PSF awarded research grants totaling over $650,000 dollars to support more than 20 plastic surgery research proposals.
ASPS/PSF leadership is committed to continuing to provide high levels of investigator-initiated research support to ensure that plastic surgeons have the needed research resources to be pioneers and innovators in advancing the practice of medicine.
Research Abstracts
Search The PSF database to have easy access to full-text grant abstracts from past PSF-funded research projects 2003 to present. All abstracts are the work of the Principal Investigators and were retrieved from their PSF grant applications. Several different filters may be applied to locate abstracts specific to a particular focus area or PSF funding mechanism.
Targeting Angiogenesis to Inhibit Heterotopic Ossification
Principal Investigator
Shailesh Agarwal MD
Shailesh Agarwal MD
Year
2015
2015
Institution
University of Michigan
University of Michigan
Funding Mechanism
Research Fellowship
Research Fellowship
Focus Area
Wounds / Scar
Wounds / Scar
Abstract
Heterotopic ossification (HO) is the abnormal formation of bone in muscle or joints. Plastic surgeons often care for patients with HO-related chronic pain, open wounds, joint restriction, and nerve entrapment. Surgical excision of HO can be attempted to restore function, but pain and limited range of motion persist. As a complication of trauma, HO presents the most important barrier to functional recovery and independence. Therapeutics such as NSAIDs or bisphosphonates are not well-tolerated by all patients and do not address the underlying cause of HO. Therefore, there is a need to identify solutions to prevent HO in patients. Based on our clinical experience and research findings, HO is preceded by excess angiogenesis. Our preliminary studies show robust vessel growth is intimately linked to ectopic bone. We have found that angiogenesis precedes HO, suggesting that targeting angiogenesis may serve as an early intervention to prevent HO. Previous studies have shown that local production of hypoxia inducible factor-1a (HIF-1a) promotes angiogenesis by inducing endothelial progenitor cell (EPC) growth and migration. We plan to improve prevention strategies for acute military and civilian injuries with high HO risk by targeting hypoxia inducible factor one alpha (HIF-1a) and subsequent EPC migration. In Aim 1, we will characterize the contribution of EPCs to HO using a mouse and rat model of HO, and human HO tissue collected from patients undergoing surgical excision. We will compare the angiogenic and osteogenic properties of EPCs from these tissues. In Aim 2, we will target HIF-1a to prevent pre-HO angiogenesis and cartilage development, thereby inhibiting HO in our mouse model. We will use three novel techniques to inhibit HIF-1a - 1) bortezomib, 2) light activated microRNA519c, and 3) Cre gene for efficient inducible HIF-1a knockout. In addition to evaluating overall HO using microCT imaging, we will assess the impact on EPCs from the injury site. We will monitor wound healing at the burn and tenotomy sites to ensure that these therapies do not alter wound healing kinetics. Upon completion of this study, we will have elucidated a therapeutic option, inhibition of angiogenesis by targeting HIF-1a, to prevent HO. Because angiogenesis precedes HO, this technique holds promise in preventing the morbidity associated with HO. Our findings will benefit patients at risk for HO after trauma/burns, spinal cord injuries, pressure ulcers, and surgical procedures.
Heterotopic ossification (HO) is the abnormal formation of bone in muscle or joints. Plastic surgeons often care for patients with HO-related chronic pain, open wounds, joint restriction, and nerve entrapment. Surgical excision of HO can be attempted to restore function, but pain and limited range of motion persist. As a complication of trauma, HO presents the most important barrier to functional recovery and independence. Therapeutics such as NSAIDs or bisphosphonates are not well-tolerated by all patients and do not address the underlying cause of HO. Therefore, there is a need to identify solutions to prevent HO in patients. Based on our clinical experience and research findings, HO is preceded by excess angiogenesis. Our preliminary studies show robust vessel growth is intimately linked to ectopic bone. We have found that angiogenesis precedes HO, suggesting that targeting angiogenesis may serve as an early intervention to prevent HO. Previous studies have shown that local production of hypoxia inducible factor-1a (HIF-1a) promotes angiogenesis by inducing endothelial progenitor cell (EPC) growth and migration. We plan to improve prevention strategies for acute military and civilian injuries with high HO risk by targeting hypoxia inducible factor one alpha (HIF-1a) and subsequent EPC migration. In Aim 1, we will characterize the contribution of EPCs to HO using a mouse and rat model of HO, and human HO tissue collected from patients undergoing surgical excision. We will compare the angiogenic and osteogenic properties of EPCs from these tissues. In Aim 2, we will target HIF-1a to prevent pre-HO angiogenesis and cartilage development, thereby inhibiting HO in our mouse model. We will use three novel techniques to inhibit HIF-1a - 1) bortezomib, 2) light activated microRNA519c, and 3) Cre gene for efficient inducible HIF-1a knockout. In addition to evaluating overall HO using microCT imaging, we will assess the impact on EPCs from the injury site. We will monitor wound healing at the burn and tenotomy sites to ensure that these therapies do not alter wound healing kinetics. Upon completion of this study, we will have elucidated a therapeutic option, inhibition of angiogenesis by targeting HIF-1a, to prevent HO. Because angiogenesis precedes HO, this technique holds promise in preventing the morbidity associated with HO. Our findings will benefit patients at risk for HO after trauma/burns, spinal cord injuries, pressure ulcers, and surgical procedures.
Biography
Dr. Shailesh Agarwal is an Assistant Professor of Surgery at Harvard Medical School and Associate Surgeon in the Division of Plastic Surgery at the Brigham and Women's Hospital. Dr. Agarwal completed his residency in plastic surgery at the University of Michigan from 2010-2018. During that time, he also completed a 2-year post-doctoral research fellowship studying pathologic wound healing with Dr. Benjamin Levi. Dr. Agarwal completed his microsurgical fellowship at the University of Chicago where he performed microsurgical reconstruction including lymphovenous bypass and vascularized lymph node transfer for patients with secondary lymphedema. At the Brigham and Women's Hospital, Dr. Agarwal performs both microsurgical and implant-based breast reconstruction, lymphedema surgery with vascularized lymph node transfer, LYMPHA for lymphedema prevention, and gender-affirming top and bottom surgery. His laboratory is focused on studying the underlying biology of lymphedema fibroadipose tissue deposition, and in developing adipocyte-based therapies for the local release of therapeutic biologic agents including peptide and microRNA.
Dr. Shailesh Agarwal is an Assistant Professor of Surgery at Harvard Medical School and Associate Surgeon in the Division of Plastic Surgery at the Brigham and Women's Hospital. Dr. Agarwal completed his residency in plastic surgery at the University of Michigan from 2010-2018. During that time, he also completed a 2-year post-doctoral research fellowship studying pathologic wound healing with Dr. Benjamin Levi. Dr. Agarwal completed his microsurgical fellowship at the University of Chicago where he performed microsurgical reconstruction including lymphovenous bypass and vascularized lymph node transfer for patients with secondary lymphedema. At the Brigham and Women's Hospital, Dr. Agarwal performs both microsurgical and implant-based breast reconstruction, lymphedema surgery with vascularized lymph node transfer, LYMPHA for lymphedema prevention, and gender-affirming top and bottom surgery. His laboratory is focused on studying the underlying biology of lymphedema fibroadipose tissue deposition, and in developing adipocyte-based therapies for the local release of therapeutic biologic agents including peptide and microRNA.