Program: Computational and Systems Biology
Current advisor: Rotating in the lab of Megan T. Baldridge, MD, PhD
Undergraduate university: Trinity College
This summer, I worked in the lab of Dr Joel Schilling studying the impact of inflammatory signaling, via Toll-like receptor 4 (TLR4), on the survival of liver resident macrophages (Kupffer cells) in response to acute LPS challenges. Non-alcoholic fatty liver disease (NAFLD), one of the most common chronic liver disorders in the US, is known to induce chronic inflammation that is characterized by loss of Kupffer cells (KCs). However, the mechanism behind this is poorly understood. Thus, I sought to establish an acute inflammation model to recreate this KC loss phenomenon in a shorter time, and then, using this model, elucidate the mechanism of KC loss in inflammatory conditions. I used in vivo and ex vivo experimental systems to probe the interplay between inflammatory signaling and macrophage survival. For ex vivo assays, I first investigated the effectiveness of previous cell death assays in bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMacs) as well as Kupffer cells (KCs). I then stimulated these cells with LPS and palmitate to compare their survival. I discovered that KCs are resistant to lipotoxic stimuli ex vivo. For in vivo assays, I challenged mice by i.p. injection of LPS and determined the degree of KC loss. The outputs of these assays were assessed using a combination of flow cytometry and immunofluorescence.