Research:

Keywords: immunology, metabolism, cancer, t cells, differentiation

Summary of Research Program

In addition to canonical activation and cytokine signaling, immune cell phenotype and function are exquisitely tuned to nutrient and metabolic conditions. Our previous work revealed that glutamine antagonism could markedly condition the differentiation of effector CD8 T cells, enhancing long-lived, memory-like phenotypes, dramatically augmenting anti-tumor responses in mouse models (Leone, et al., Science, 2019). Building on these observations, our lab is interested in elucidating cellular mechanisms of adaptive immune response to metabolic perturbations. Our approach includes assessment of transcription factor modulation, metabolic enzyme moonlighting, metabolically responsive posttranslational modifications (e.g., methylation, acetylation), spliceosomal modulation, cellular stress response, as well as bioactive lipid signaling and cancer/immune cell co-metabolism. This work requires integration of a broad range of techniques including high-dimensional flow cytometry, mass spectrometry (e.g., metabolomics, stable isotope tracing), metabolic flux analyses, proteomics, transcriptomics and epigenomics, CRISPR/Cas9 gene editing, microscopy and metabolic imaging agents. Specific areas of interest include ACSS2 mediated epigenetic modulation, metabolic modulation of FOXO1, and the role of pyruvate and glutamate metabolism in cellular redox homeostasis. We employ an extensive range of immunologic models in mice, in vitro studies, as well as patient samples. Our goal is to elucidate fundamental cellular processes activated in response to metabolic events that have broad implications for development of immune-based therapeutics.

Publications and Interests: https://jhu.pure.elsevier.com/en/persons/robert-leone