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.
Single cell transcriptional analysis of fibroblasts in Dupuytren disease
Principal Investigator
Janos Barrera MD
Janos Barrera MD
Year
2020
2020
Institution
Stanford University
Stanford University
Funding Mechanism
Combined Pilot Research Grant
Combined Pilot Research Grant
Focus Area
Hand of Upper Extremity, Wounds/Scar
Hand of Upper Extremity, Wounds/Scar
Abstract
Project Summary: Dupuytren disease, affecting over 20 million Americans, remains one of the most challenging problems faced by hand surgeons due to the unpredictable progression of disease, inadequate treatment options, and high recurrence rates. The myofibroblast has been implicated as the primary cell responsible for matrix deposition and contraction in a variety of disease states. Our laboratory recently performed a meta-analysis of publicly available Dupuytren gene expression data, and found correlations with calcium channel function, as well as mesenchymal stem cell and fibroblast proliferation. However, recent developments in our understanding of fibroblasts include the realization of substantial heterogeneity within these cell populations. For example, it was recently shown that CD26+ fibroblasts constitute a distinct subpopulation, which is the primary cell type for excessive collagen deposition during wound-healing associated fibrosis. Similarly, heterogeneity in fibroblasts mediating pulmonary and renal fibrosis have also been described. These results indicate that a method for high-resolution analysis of these cell subpopulations is needed to better understand the role that these cells play in disease pathogenesis. Over the past 15 years, the Gurtner laboratory has developed a unique and robust platform for cell detection and selection that we have validated in a number of published studies and can be used to identify functionally significant subpopulations within heterogenous populations. Here, we will apply single cell RNA sequencing (scRNA-seq) to human Dupuytren tissue, to identify and characterize the populations of fibroblasts responsible for its pathogenesis. We will then test two therapeutic strategies for reducing fibrosis in vivo using a rat model. Carboxyamidotriazole (CAI), a commercially available calcium channel blocker and chemotherapeutic that was identified by our recent meta-analysis data, will be tested for in vivo fibrosis reduction. Depletion of a known fibrogenic population of fibroblasts (CD26+), as well as any subpopulations of interest identified through scRNA-seq, will also be examined for changes in fibrosis in vivo. By identifying the subpopulations responsible for Dupuytren disease, this project will enable the development of improved diagnostics, predictive tools and treatment modalities for this challenging condition before it causes significant functional impairment. Impact Statement: Dupuytren disease significantly affects patient quality of life and poses direct and indirect costs to society through increased healthcare spending and loss of productivity. Currently, we are unable to predict if patients will progress toward severe joint contracture, or if they will remain without functional impairment for decades. By identifying the fibroblast subpopulation responsible for Dupuytren disease, we may be able to determine which patients are at highest risk for disease progression. Additionally, a thorough understanding of the signaling networks in Dupuytren disease could help identify new treatment modalities. These findings could allow hand surgeons to implement targeted therapy in high-risk patients before their disease causes functional impairment.
Project Summary: Dupuytren disease, affecting over 20 million Americans, remains one of the most challenging problems faced by hand surgeons due to the unpredictable progression of disease, inadequate treatment options, and high recurrence rates. The myofibroblast has been implicated as the primary cell responsible for matrix deposition and contraction in a variety of disease states. Our laboratory recently performed a meta-analysis of publicly available Dupuytren gene expression data, and found correlations with calcium channel function, as well as mesenchymal stem cell and fibroblast proliferation. However, recent developments in our understanding of fibroblasts include the realization of substantial heterogeneity within these cell populations. For example, it was recently shown that CD26+ fibroblasts constitute a distinct subpopulation, which is the primary cell type for excessive collagen deposition during wound-healing associated fibrosis. Similarly, heterogeneity in fibroblasts mediating pulmonary and renal fibrosis have also been described. These results indicate that a method for high-resolution analysis of these cell subpopulations is needed to better understand the role that these cells play in disease pathogenesis. Over the past 15 years, the Gurtner laboratory has developed a unique and robust platform for cell detection and selection that we have validated in a number of published studies and can be used to identify functionally significant subpopulations within heterogenous populations. Here, we will apply single cell RNA sequencing (scRNA-seq) to human Dupuytren tissue, to identify and characterize the populations of fibroblasts responsible for its pathogenesis. We will then test two therapeutic strategies for reducing fibrosis in vivo using a rat model. Carboxyamidotriazole (CAI), a commercially available calcium channel blocker and chemotherapeutic that was identified by our recent meta-analysis data, will be tested for in vivo fibrosis reduction. Depletion of a known fibrogenic population of fibroblasts (CD26+), as well as any subpopulations of interest identified through scRNA-seq, will also be examined for changes in fibrosis in vivo. By identifying the subpopulations responsible for Dupuytren disease, this project will enable the development of improved diagnostics, predictive tools and treatment modalities for this challenging condition before it causes significant functional impairment. Impact Statement: Dupuytren disease significantly affects patient quality of life and poses direct and indirect costs to society through increased healthcare spending and loss of productivity. Currently, we are unable to predict if patients will progress toward severe joint contracture, or if they will remain without functional impairment for decades. By identifying the fibroblast subpopulation responsible for Dupuytren disease, we may be able to determine which patients are at highest risk for disease progression. Additionally, a thorough understanding of the signaling networks in Dupuytren disease could help identify new treatment modalities. These findings could allow hand surgeons to implement targeted therapy in high-risk patients before their disease causes functional impairment.
Biography
Dr. Janos Barrera is a plastic surgery resident at Stanford and currently working as a postdoctoral research fellow in the Hagey Laboratory for Pediatric Regenerative Medicine at Stanford University School of Medicine under the mentorship of Dr. Geoffrey Gurtner. Dr. Barrera completed his medical degree at Stanford after obtaining his bachelor’s degree in Biochemistry with Honors from the University of Washington. Since joining the Gurtner laboratory, Dr. Barrera has been investigating cellular and molecular mechanisms of mammalian regeneration, including the application of stem cell and small molecule-based therapies for improving wound healing.
Dr. Janos Barrera is a plastic surgery resident at Stanford and currently working as a postdoctoral research fellow in the Hagey Laboratory for Pediatric Regenerative Medicine at Stanford University School of Medicine under the mentorship of Dr. Geoffrey Gurtner. Dr. Barrera completed his medical degree at Stanford after obtaining his bachelor’s degree in Biochemistry with Honors from the University of Washington. Since joining the Gurtner laboratory, Dr. Barrera has been investigating cellular and molecular mechanisms of mammalian regeneration, including the application of stem cell and small molecule-based therapies for improving wound healing.