Melanie Martinsen
Understanding and Enhancing Neutrophil Progenitor Engraftment
Abstract
Neutrophils are our first defenders against bacterial and fungal infections. This proposal aims to develop neutrophil progenitors (NPs) as an “off-the-shelf” cellular therapy capable of attenuating periods of neutropenia or neutrophil dysfunction. Our lab has developed conditionally-immortalized murine NP cell lines that have the unique ability to robustly engraft in the bone marrow of naïve mice and rapidly generate mature, functional neutrophils within days and for a period of two weeks. Preliminary studies show that these NPs cannot however engraft in mice of a different strain as an allograft, suggesting immune barriers may mediate graft rejection. I hypothesize that neutrophil progenitors can be genetically engineered to enhance engraftment and evade transplantation barriers. These studies will elucidate the mechanisms and barriers of NP engraftment, and significantly impact human health by bringing NPs as a cellular therapy closer to clinical development.
This fellowship provides critical support for my research developing a cell therapy for immunocompromised patients. This training will equip me with the skills to identify gaps in clinical care and bridge them through innovative, patient-centered research.
