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.
Preventing Scar Contracture Formation by Inhibiting ROCK
Principal Investigator
Howie Levinson MD, FACS
Howie Levinson MD, FACS
Year
2010
2010
Institution
Duke University Medical Center
Duke University Medical Center
Funding Mechanism
National Endowment for Plastic Surgery Grant
National Endowment for Plastic Surgery Grant
Focus Area
Wounds / Scar
Wounds / Scar
Abstract
Scar contracture is estimated to affect more than 40 million people worldwide. There are no effective treatments to prevent contractures. The long-term objective of this research is to develop a drug to prevent scar contracture formation. Contractures develop gradually, and as they progress the scar matrix becomes increasingly stiff. Contractures are believed to be caused by fibroblast contractility, which is stimulated by Rho kinase (ROCK). It is hypothesized that ROCK activation causes scar contracture formation and that increasing matrix stiffness acts synergistically with TGF-beta to promote ROCK activation through Rho A. Two Specific Aims are proposed in this innovative proposal to test the hypothesis. Successful completion of the Specific Aims will further the understanding of the pathogenesis of scar contracture and identify a drug to prevent contracture formation.
Specific Aim 1. To determine how increasing tensile strain works synergistically with TGF-beta to promote ROCK activation. In the heart, ROCK is stimulated by increasing mechanical strain and in the lung ROCK is activated by TGF-beta stimulation of Rho A. The effect of increasing mechanical strain and TGF-beta stimulation on ROCK induced fibroblast contractility in the skin is unknown. This Specific Aim will use polyacrylamide gels of varying stiffnesses (soft (1kPa), and medium (20kPa)) with glass slides as a positive control (>100kPa), to test how changes in matrix rigidity act synergistically with TGF-beta to alter ROCK mediated fibroblast contractility through Rho A.
Specific Aim 2. To determine the efficacy of ROCK inhibition in contracture prevention. The FDA approved drug, fasudil, has been shown to prevent lung, liver, and kidney fibrosis. Fasudil will be used to test whether ROCK inhibition prevents rat wound contraction. Osmotic pumps will be subcutaneously implanted to continuously deliver systemic fasudil. The effects of fasudil on wound contraction will be quantified by planimetry.
Scar contracture is estimated to affect more than 40 million people worldwide. There are no effective treatments to prevent contractures. The long-term objective of this research is to develop a drug to prevent scar contracture formation. Contractures develop gradually, and as they progress the scar matrix becomes increasingly stiff. Contractures are believed to be caused by fibroblast contractility, which is stimulated by Rho kinase (ROCK). It is hypothesized that ROCK activation causes scar contracture formation and that increasing matrix stiffness acts synergistically with TGF-beta to promote ROCK activation through Rho A. Two Specific Aims are proposed in this innovative proposal to test the hypothesis. Successful completion of the Specific Aims will further the understanding of the pathogenesis of scar contracture and identify a drug to prevent contracture formation.
Specific Aim 1. To determine how increasing tensile strain works synergistically with TGF-beta to promote ROCK activation. In the heart, ROCK is stimulated by increasing mechanical strain and in the lung ROCK is activated by TGF-beta stimulation of Rho A. The effect of increasing mechanical strain and TGF-beta stimulation on ROCK induced fibroblast contractility in the skin is unknown. This Specific Aim will use polyacrylamide gels of varying stiffnesses (soft (1kPa), and medium (20kPa)) with glass slides as a positive control (>100kPa), to test how changes in matrix rigidity act synergistically with TGF-beta to alter ROCK mediated fibroblast contractility through Rho A.
Specific Aim 2. To determine the efficacy of ROCK inhibition in contracture prevention. The FDA approved drug, fasudil, has been shown to prevent lung, liver, and kidney fibrosis. Fasudil will be used to test whether ROCK inhibition prevents rat wound contraction. Osmotic pumps will be subcutaneously implanted to continuously deliver systemic fasudil. The effects of fasudil on wound contraction will be quantified by planimetry.
Biography
Howard Levinson, MD, FACS is a double board certified General Surgeon and Plastic and Reconstructive Surgeon at Duke University Medical Center (DUMC). He is an Associate Professor in the Departments of Surgery and Pathology. Dr Levinson is the Director of Plastic Surgery Research and is the Principal Investigator of the Wound Healing and Fibrosis Laboratory at DUMC. Dr Levinson has an active clinical practice. He cares for patients both at DUMC and the Veterans Administration Hospital in Durham, North Carolina. Dr Levinson performs clinical research and leads a translational research team which is rooted in the basic science laboratory. He holds several translational patents. His team uses contemporary in vitro and in vivo disease models to understand the mechanisms of skin wound healing and scarring in both rodents and swine. His laboratory is funded by intramural as well as extramural grants. His funding portfolio includes past and present grants from industry sponsored research, foundation and society funding, and grants from the National Institutes of Health and Howard Hughes Medical Institute.
Dr Levinson is also a national recognized key opinion leader in the field of skin regeneration as is evidenced by his consulting for GlaxoSmithKline, Johnson and Johnson, Heraeus Pharmaceuticals, Exoxemis, Allergan. He serves on the Wound Care Advisory board for Cardinal Health. He had served on multiple study sections for Department of Defense and the Plastic Surgery Foundation and has multiple collaborations with investigators both within and outside of DUMC. He has served as an ad-hoc reviewer for several scientific journals including The New England Journal of Medicine, Annals of Surgery, The American Journal of Physiology: Cell Physiology, e-PLOS, Journal of Surgical Research, Plastic and Reconstructive Surgery, and Molecular and Cellular Biochemistry.
Howard Levinson, MD, FACS is a double board certified General Surgeon and Plastic and Reconstructive Surgeon at Duke University Medical Center (DUMC). He is an Associate Professor in the Departments of Surgery and Pathology. Dr Levinson is the Director of Plastic Surgery Research and is the Principal Investigator of the Wound Healing and Fibrosis Laboratory at DUMC. Dr Levinson has an active clinical practice. He cares for patients both at DUMC and the Veterans Administration Hospital in Durham, North Carolina. Dr Levinson performs clinical research and leads a translational research team which is rooted in the basic science laboratory. He holds several translational patents. His team uses contemporary in vitro and in vivo disease models to understand the mechanisms of skin wound healing and scarring in both rodents and swine. His laboratory is funded by intramural as well as extramural grants. His funding portfolio includes past and present grants from industry sponsored research, foundation and society funding, and grants from the National Institutes of Health and Howard Hughes Medical Institute.
Dr Levinson is also a national recognized key opinion leader in the field of skin regeneration as is evidenced by his consulting for GlaxoSmithKline, Johnson and Johnson, Heraeus Pharmaceuticals, Exoxemis, Allergan. He serves on the Wound Care Advisory board for Cardinal Health. He had served on multiple study sections for Department of Defense and the Plastic Surgery Foundation and has multiple collaborations with investigators both within and outside of DUMC. He has served as an ad-hoc reviewer for several scientific journals including The New England Journal of Medicine, Annals of Surgery, The American Journal of Physiology: Cell Physiology, e-PLOS, Journal of Surgical Research, Plastic and Reconstructive Surgery, and Molecular and Cellular Biochemistry.