Grants We Funded
Grant applicants for the 2023 cycle requested a total of nearly $4 million dollars. The PSF Study Section Subcommittees of Basic & Translational Research and Clinical Research evaluated nearly 140 grant applications on the following topics:
The PSF awarded research grants totaling over $1 million dollars to support nearly 30 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.
Inducible Lymphovenous Shunts using Tissue Nanotransfection Technology
Principal Investigator
Al Hassanein MD, MMSc, FACS
Al Hassanein MD, MMSc, FACS
Year
2020
2020
Institution
Indiana University
Indiana University
Funding Mechanism
PSRC/ PSF Research Grant
PSRC/ PSF Research Grant
Focus Area
Microsurgery, General Reconstructive
Microsurgery, General Reconstructive
Abstract
Project Summary: Lymphedema refers to swelling of limbs due to accumulation of lymphatic fluid and is caused by the removal of or damage to lymph nodes. If not congenital, (rare type called primary lymphedema) lymphedema is a secondary manifestation to cancer treatment. It usually occurs after cancer surgery or due to radiation therapy. Currently it affects around 250 million people worldwide. There is no treatment to lymphedema. The condition is primarily managed through surgical interventions of lymphovenous anastomosis (LVA) which relies on fusing the lymphatic vessels with the veins at the affected site. This helps to drain the lymphatic fluid back to the circulatory system. During fetal development the lymphatic vessels develop from veins. Once the lymphatic vessels are formed genes, SH2 domain-containing leukocyte protein 76 (Slp-76) and spleen tyrosine kinase (Syk) are activated which ensures that lymphatic vessels stay separate to veins. Here, we propose to turn on the developmental switch of lymphangiogenesis to stimulate LVA formation without surgical intervention. This is proposed by focal silencing genes Slp-76 and Syk in mice tail model of lymphedema. The gene silencing will be done through novel, deterministic and platform technology of tissue nanotransfection (TNT). TNT is a validated non-viral gene delivery technology. The technology is safe and does not pose immunogenic or oncogenic threat of viral vectors. We have proposed two aims to test the feasibility of the concept. In Aim 1: Develop and validate tissue nanotransfection (TNT) based approach to deliver anti-sense oligos against Slp-76 and Syk to murine tail vasculature affected by lymphedema Aim 2: Test whether knockdown approaches to Slp-76 and Syk in the lymphedematous mouse tail achieve lymphovenous shunting and improves lymphedema resolution. Impact Statement: Lymphedema results from lymphatic dysfunction causing extremity swelling from inadequate fluid clearance, adipose deposition and fibrosis. There is no cure for to lymphedema. The condition is managed through conservative (e.g. compression) and surgical interventions. Surgical intervention is by lymphovenous anastomosis (LVA) in which <1mm lymphatic vessels are microsurgically connected with veins. We aim to induce lymphovenous shunts similar to LVA without surgical intervention by silencing genes (Slp-76 and Syk) which prevent lymphatic and venous fusion. This is proposed through novel technology of tissue nano-transfection (TNT). TNT mediated non-viral gene delivery has been previously developed and validated by my collaborators. The results of this study will be clinically translatable.
Project Summary: Lymphedema refers to swelling of limbs due to accumulation of lymphatic fluid and is caused by the removal of or damage to lymph nodes. If not congenital, (rare type called primary lymphedema) lymphedema is a secondary manifestation to cancer treatment. It usually occurs after cancer surgery or due to radiation therapy. Currently it affects around 250 million people worldwide. There is no treatment to lymphedema. The condition is primarily managed through surgical interventions of lymphovenous anastomosis (LVA) which relies on fusing the lymphatic vessels with the veins at the affected site. This helps to drain the lymphatic fluid back to the circulatory system. During fetal development the lymphatic vessels develop from veins. Once the lymphatic vessels are formed genes, SH2 domain-containing leukocyte protein 76 (Slp-76) and spleen tyrosine kinase (Syk) are activated which ensures that lymphatic vessels stay separate to veins. Here, we propose to turn on the developmental switch of lymphangiogenesis to stimulate LVA formation without surgical intervention. This is proposed by focal silencing genes Slp-76 and Syk in mice tail model of lymphedema. The gene silencing will be done through novel, deterministic and platform technology of tissue nanotransfection (TNT). TNT is a validated non-viral gene delivery technology. The technology is safe and does not pose immunogenic or oncogenic threat of viral vectors. We have proposed two aims to test the feasibility of the concept. In Aim 1: Develop and validate tissue nanotransfection (TNT) based approach to deliver anti-sense oligos against Slp-76 and Syk to murine tail vasculature affected by lymphedema Aim 2: Test whether knockdown approaches to Slp-76 and Syk in the lymphedematous mouse tail achieve lymphovenous shunting and improves lymphedema resolution. Impact Statement: Lymphedema results from lymphatic dysfunction causing extremity swelling from inadequate fluid clearance, adipose deposition and fibrosis. There is no cure for to lymphedema. The condition is managed through conservative (e.g. compression) and surgical interventions. Surgical intervention is by lymphovenous anastomosis (LVA) in which <1mm lymphatic vessels are microsurgically connected with veins. We aim to induce lymphovenous shunts similar to LVA without surgical intervention by silencing genes (Slp-76 and Syk) which prevent lymphatic and venous fusion. This is proposed through novel technology of tissue nano-transfection (TNT). TNT mediated non-viral gene delivery has been previously developed and validated by my collaborators. The results of this study will be clinically translatable.
Biography
I am a plastic surgeon specializing in microsurgery in my third year of practice at Indiana University with formal training in clinical and translational research. I am an Assistant Professor at Indiana University School of Medicine. I graduated Magna Cum Laude with a Bachelor’s of Science in Biochemistry at the University of Illinois and completed medical school at the University of Illinois College of Medicine. I finished a general surgery residency at the University of California San Diego, plastic surgery residency at Harvard, and a microsurgery fellowship Johns Hopkins. I completed a 2-year research fellowship in the laboratory of Dr. Arin Greene at Boston Children’s Hospital studying cranial osseous healing as well as vascular malformations and tumors. I earned a Master in Medical Sciences degree in translational and clinical research at Harvard Medical School.
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In my clinical practice, I perform oncological reconstruction and treat lymphedema, including lymphovenous anastomosis (LVA). LVA is a microsurgical technique used to treat lymphedema with bypassing proximal obstructed lymphatics. My research interest is also in lymphedema. During my protected time, I am an investigator at the Indiana Center of Regenerative Medicine. I am collaborating with Dr. Mithun Sinha and Dr. Chandan Sen to improve lymphedema in a mouse tail model by inducing physiological lymphovenous anastomoses using Tissue Nano-transfection (TNT).
I am a plastic surgeon specializing in microsurgery in my third year of practice at Indiana University with formal training in clinical and translational research. I am an Assistant Professor at Indiana University School of Medicine. I graduated Magna Cum Laude with a Bachelor’s of Science in Biochemistry at the University of Illinois and completed medical school at the University of Illinois College of Medicine. I finished a general surgery residency at the University of California San Diego, plastic surgery residency at Harvard, and a microsurgery fellowship Johns Hopkins. I completed a 2-year research fellowship in the laboratory of Dr. Arin Greene at Boston Children’s Hospital studying cranial osseous healing as well as vascular malformations and tumors. I earned a Master in Medical Sciences degree in translational and clinical research at Harvard Medical School.
<br />
In my clinical practice, I perform oncological reconstruction and treat lymphedema, including lymphovenous anastomosis (LVA). LVA is a microsurgical technique used to treat lymphedema with bypassing proximal obstructed lymphatics. My research interest is also in lymphedema. During my protected time, I am an investigator at the Indiana Center of Regenerative Medicine. I am collaborating with Dr. Mithun Sinha and Dr. Chandan Sen to improve lymphedema in a mouse tail model by inducing physiological lymphovenous anastomoses using Tissue Nano-transfection (TNT).