BME PhD Dissertation Defense: Delaney Gray Scherr

Title: "Engineering the lymphatic system: an in vitro approach to multi‑scale study of lymphatic vascular function"

Advisory Committee: Joyce Y. Wong, Ph.D. – BME, MSE (Chair), BU Christopher S. Chen, M.D., Ph.D. – BME, MSE (Research Advisor), BU Hadi T. Nia, Ph.D. – BME, BU Diane Bielenberg, Ph.D. – Surgery, HMS John T. Ngo, Ph.D. – BME, BU

Abstract: Lymphedema, lipedema, and related lymphatic disorders collectively affect hundreds of millions of people worldwide, disproportionately burden women, and lack disease‑modifying treatments, in large part because we lack human experimental models that connect molecular changes in lymphatic endothelium to drainage‑relevant transport. This dissertation develops two such in vitro platforms. First, a tape‑based microfluidic device supports independently perfusable, self‑assembled human blood and lymphatic microvascular networks within a shared fibrin matrix, reconstructing the coupled blood–interstitium–lymphatic interface at capillary scale. This platform enables size‑selective solute and lipid transport from blood to lymphatic vessels under physiologic‑like hydrostatic gradients and recapitulates cytokine‑ and chemokine‑regulated T cell trafficking from blood to lymphatic vessels. Second, a reductionist 2D model drives primary adult human dermal lymphatic endothelial cells into a button‑like junctional state with discontinuous VE‑cadherin puncta, oak‑leaf morphology, high‑resistance barrier function, and apparent unidirectional, pressure‑dependent macromolecular transport. Using this system, glucocorticoid receptor knockdown and IL‑1β treatment are shown to drive distinct junctional trajectories away from the drainage‑competent button‑like state with characteristic morphological, barrier, and transcriptional signatures, supporting a model in which lymphatic junctions occupy a continuum of functionally distinct states shaped by glucocorticoid signaling, inflammatory NF‑κB programs, and Rho‑ROCK–mediated mechanobiology. Together, these platforms provide human‑relevant experimental foundations for dissecting the molecular basis of lymphatic capillary drainage and for identifying targets to preserve lymphatic function in disease.