Grants Funded

Abstract

Project Summary: Secondary lymphedema, a debilitating condition affecting over 5 million individuals in the US after lymphadenectomy for cancer surgery, results in progressive limb swelling and irreversible fibroadipose tissue deposition. This pathological process leads to limb hypertrophy, chronic pain, open wounds, and disability. Our goal is to identify an effective, non-surgical strategy to mitigate chronic lymphedema by targeting fibrofatty tissue deposition. In this proposal, I will use a mouse model of hindlimb secondary lymphedema induced via surgical excision of the hindlimb draining lymph nodes and the femoral lymphatic vessel. In Aim 1, I will examine how rosiglitazone, an adipogenic agent that augments signaling through peroxisome proliferator-activated gamma (PPARy), modifies inflammation and mesenchymal cell fate in lymphedema when delivered at discrete timepoints, including during the immediate and post-inflammatory phases. In Aim 2, I will further refine, validate, and examine a topical formulation of rosiglitazone to treat lymphedema when applied locally, while also limiting toxic systemic effects. To achieve my research endeavors and advance my career goal of becoming an academic plastic surgeon, I have joined the laboratory of Dr. Shailesh Agarwal, a surgeon-scientist in the Department of Surgery studying the pathology of adipose tissue in lymphedema. Dr. Arin Greene, expert in pediatric vascular anomalies and lymphedema, will serve as a co-mentor for this proposal. Under their mentorship, I will set out to achieve my research objectives through a rigorous training plan that initiated in July 2023 and will continue through June 2025. I have developed a schedule for individual and laboratory meetings with both mentors. I have access to resources and equipment available in Dr. Agarwal's lab. As a member of the Harvard community, I participate in courses offered by Harvard Medical School, including seminars on developing laboratory research skills and workshops on advanced laboratory techniques, many of which I have already completed. Long-term, my ambition is to be an academic surgeon-scientist with an NIH-funded laboratory that investigates treatment for clinically debilitating and challenging conditions. I am confident that with the support of the PSF Research Fellowship, I will make significant strides in my maturation as a physician-scientist with the goal of serving as a scientific and clinical leader whose research impacts the lives of patients.

Impact Statement: This research proposal is relevant to public health because it examines a method to treat secondary lymphedema, a condition which impacts over 5 million cancer patients in the United States. This proposal seeks to examine how a therapeutic agent with a history of previous FDA approval for other indications, reduces the permanent limb hypertrophy observed in patients with chronic lymphedema. Successful execution of this proposal would have wide-ranging impacts on the practice of plastic surgery with the translation of a topical therapeutic agent for secondary lymphedema, a debilitating condition that currently lacks reliable, long-term treatment.

Biography
I completed my undergraduate training at Tufts University (2011 – 2015) where I studied Biopsychology. During that time, I was involved in basic science research using mice to study the effects of alcohol on stress. I worked in the laboratory of Dr. Diana Bianchi, who was then recruited to the NIH, where she is now the Director of NICHD. After graduating, I joined her laboratory at NIH studying prenatal treatments for Down syndrome. This work led to 4 publications which I co-authored with Dr. Bianchi as the senior author. I matriculated at the UCF College of Medicine in 2017 under a merit-based scholarship. I continued my laboratory research while at UCF and had the honor of being inducted to the institution’s AOA chapter. I then began my General Surgery residency at Brigham and Women’s Hospital in June 2021 where I balanced a demanding clinical load with my desire to pursue research. I identified the lab of Dr. Shailesh Agarwal as a place where I could combine my interest in plastic surgery with my desire to grow as a physician-scientist. Under his guidance, I have started to investigate treatment for lymphedema, a debilitating, incurable condition. I will take two years of uninterrupted, dedicated research time in Dr. Agarwal’s laboratory that commenced on July 1, 2023. Upon completion of my General Surgery residency at BWH, I plan to pursue a fellowship in plastic surgery. Long-term, I hope to establish myself as a plastic surgeon and a laboratory researcher.