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Michigan Postdoctoral Pioneer Program, 2020

Collaborative PIs

Mentor

Deepak Nagrath, Ph.D.

Associate Professor
Department of Biomedical Engineering
Department of Chemical Engineering
University of Michigan
https://nagrath.bme.umich.edu/
Email:
dnagrath@umich.edu

Co - Mentor

Venkat Keshamouni, Ph.D.

ASSOCIATE PROFESSOR OF INTERNAL MEDICINE, PULMONARY & CRITICAL CARE DIVISION
https://cancerbio.medicine.umich.edu/venkat-keshamouni-phd
Email:
vkeshamo@umich.edu

Abstract:

Title:

Metabolic engineering of CAR-NK cells

Metabolism is an important driver of cancer progression influencing the growth and function of all cell types in the tumor microenvironment, including Natural Killer (NK), a key first line of defense against malignant cells. Tumor altered metabolic changes such as high levels of aerobic glycolysis, oxygen deprivation and competition for critical nutrients, all contribute to the suppression of function and metabolic reprogramming of NK cells. In addition, NK cells are emerging as an important alternative to T cells for chimeric antigen receptor (CAR) based immunotherapies, as they do not require strict HLA matching or carry the risk of graft-versus-host disease. Therefore, understanding the mechanisms and pathways regulating such immunometabolic changes is critical for developing new generation of NK cell-based immunotherapies. The goal of this project is to identify tumor-induced immunometabolic barriers in NK cells, investigate how expression of CARs modulate those barriers, with the aim of engineering NK-tailored CARs with favorable energetics and optimum activity. Project involves the use of cutting edge approaches including single cell proteomics, transcriptomics, metabolic flux, bioenergetics, cellular engineering and mouse models of lung cancer. The selected candidate will interact and work together with PIs, Nagrath Lab, and Keshamouni Lab. This will be an excellent opportunity for a candidate to make strong contributions in immunometabolism. 

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