Grants We Funded

Abstract

Impact Summary: Lymphedema is a common complication of cancer treatment and constitutes a significant clinical and economic burden for millions of patients. We aim to utilize immunosequencing techniques to unveil the T cell repertoire activated following lymphatic injury. Successful sequencing of the T cell population will lead to the discovery of putative antigens that play a role in disease development.

Project Summary: Lymphedema is a significant clinical problem for which there is no cure. Despite recent advances in the study of lymphedema pathophysiology, treatment options are limited by a lack of clear understanding of the mechanisms mediating T cell activation following lymphatic injury. We seek to uncover the pathogenic immune responses in lymphedema by sequencing the T cell repertoire, subsequently, enabling the identification of specific T cell-antigen interactions that promote lymphatic dysfunction. We have previously demonstrated that CD4+ T cells are necessary for the pathological changes observed in lymphedema, such as fibrosis, reduced lymphatic pumping, and impaired lymphangiogenesis. We further observed that T cell-APC interactions play a critical role in initiating these inflammatory responses. Building upon this work, this current proposal is based on the central hypothesis that T cell immune responses in lymphedema are oligoclonal in nature and that T cell clones expanding in lymphedematous tissue are generated in response to specific antigens. We have two primary aims: Aim 1 will focus on identifying the clonality of the T cell repertoire in lymphedematous tissue using T cell receptor (TCR) sequencing, while Aim 2 seeks to determine the specific antigens driving the clonal expansion of these T cell populations. Both aims seek to identify a common antigen driving the expansion of pathogenic T cell clones in lymphedema. The goal of this proposal is to identify a common clonal architecture between patients with lymphedema, allowing for early detection of at risk-patients. This discovery could pave the way for the development of novel therapies that target clones early in disease to ultimately prevent disease progression.

Biography
Dr. Adana- Christine Campbell is a research scholar in the laboratory of Dr. Babak J. Mehrara at Memorial Sloan-Kettering Cancer Center in New York, NY. With Dr. Mehrara’s guidance, she will investigate the immunologic mechanisms implicated in the development of lymphedema, with the goal of discovering target therapies that prevent disease progression. Dr. Campbell was raised in Brooklyn, New York and later migrated to North Carolina where she completed her undergraduate studies in 2014 in Cellular and Molecular Biology at Appalachian State University. She obtained her medical degree in 2019 from St. Georges University School of Medicine in Grenada, W.I. Prior to this current research position, Dr. Campbell completed two years of general surgery residency at Metropolitan Hospital in New York. She is passionate about fostering inclusion and diversity in the field of plastic surgery and has a long-term career goal of becoming an academic reconstructive surgeon.