Preoperative exercise therapy modulates hepatic neutrophil extracellular trap formation

Feinstein Institute For Medical Research, Manhasset NY

Investigators

Linked publications & trials

Abstract

PROJECT DESCRIPTION: The goal of this Supplement application is to support a Baccalaureate’s degree holder from underrepresented minority group, for pursuing a career in biomedical research. The candidate will receive personized mentorship and support to enhance her medical research experience and experimental skills to determine the mechanism by which preoperative exercise therapy modulates the capability of neutrophils forming neutrophil extracellular traps (NETs), which is highly relevant to the parent grant (R01GM137203) entitled "Preoperative exercise therapy for surgery triggered inflammation". Liver ischemia and reperfusion (I/R) is an unavoidable consequence of major liver resection and liver transplantation that leads to significant morbidity, mortality, and costs after liver surgery. However, previous strategies to protect the liver from I/R injury have focused on one specific known injury mechanisms, leaving intact other detrimental processes. Pre/post-operative exercise facilitates recovery after major abdominal surgery. It is known that exercise confers beneficial effects on the surgical outcome by regulating multiple mechanisms, including alteration of quantity and function of innate immune cells to provide an anti-inflammatory environment. We have discovered that preoperative exercise therapy (PET) significantly reduced serum aminotransferase levels (liver damage) and expression of cytokines and chemokines (inflammatory responses) during liver I/R via metabolic reprogramming Kupffer cells from pro-inflammatory to anti-inflammatory phenotype. However, even though cellular energy metabolism and mitochondrial biogenesis play a critical role in the immune response, the effects of PET-induced changes in neutrophils forming neutrophil extracellular traps (NETs) have never been studied. The undergraduate summer research program at Feinstein Institutes for Medical Research is a well-established research program that support undergraduate students who are considering pursuing biomedical research careers in cutting-edge scientific environments during the summer. Our proposed studies which will be conducted by undergraduate student will significantly expand the scope of the parent R01 award by interrogating two new questions related to those already being investigated in the parent R01 award: 1) What is the role of PET in the transcriptomic changes of infiltrating neutrophils after liver I/R? 2) Do PET- trained KCs suppress NET formation during liver I/R? In summary, the mentored studies will provide valuable training and mentorship to the candidate, contributing to her career development and increasing diversity in biomedical research and will significantly expand the current understanding of the underlying mechanistic mechanisms by which PET prevent surgical stress-induced organ injury via modulating NET formation and evaluate novel potential therapeutic targets, and assess promising novel treatments for patients undergoing surgery.