Flavell Lab Research
Our research uses transgenic and gene-targeted mice to study Innate and Adaptive immunity, T cell tolerance and activation in immunity and autoimmunity, apoptosis, and regulation of T cell differentiation.
- Inflammation and Mucosal Immunity
- Lymphocyte Biology
- Humanized Mice
- RNA World
While transcriptional programming of immune cell differentiation and function has been a well-studied topic of research, the last decade has witnessed a resurgence of interest in how cell metabolism potentiates the biochemistry of these processes. Our lab is interested both in how cell metabolic processes dictate immune responses on the cellular level as well as how organismal and tissue nutrient environments impact immune function. Our current research focuses on lipid, carbohydrate, and amino acid metabolism of lymphocytes and innate immune cells, as well as the biology of intestinal, mucosal, and adipose tissues.
Integrating our long-term focus on T cell differentiation, recent work by Bailis, Shyer et al. demonstrated separable roles for mitochondrial complex I and complex II driven electron transport systems in CD4+ T cell proliferation and Th1 differentiation/IFNg secretion. We found that during early T cell activation, TCA cycling enables the malate/aspartate shuttle and citrate export to produce acetyl-CoA necessary for histone acetylation and epigenetic remodeling, highlighting the reciprocal regulation of cell metabolism and differentiation through changes in gene expression, an ongoing area of interest for our lab. While much immunometabolism has focused on central nodes such as mTOR, we continue to investigate the complex network of biochemical interactions comprising the metabolic-immune axis in multiple cell types with high resolution via forward genetic and chemical screening approaches including CRISPR/Cas9 screening.
Bailis W, Shyer JA, Zhao J, Canaveras JCG, Al Khazal FJ, Qu R, Steach HR, Bielecki P, Khan O, Jackson R, Kluger Y, Maher LJ 3rd, Rabinowitz J, Craft J, Flavell RA. Distinct modes of mitochondrial metabolism uncouple T cell differentiation and function.Nature .
(2019) Jul;571(7765):403-407. doi: 10.1038/s41586-019-1311-3. Epub 2019 Jun 19;573(7773):E2. PMID: 31217581; PMCID: PMC6939459.