Maria Bettini
Education and Training
2001 BS East Tennessee State University
2006 PhD Emory University
2006-2008 Postdoctoral training Emory University
2008-2013 Postdoctoral training St Jude Children's Research Hospital
Research Interests
Our group has been working to understand how T cell receptor guides T cell fate decisions of autoimmune and regulatory Foxp3+ T cells. T cell responses in autoimmunity develop under a unique set of conditions: relatively low TCR affinity, lack of danger signals, and chronic antigen stimulation. We are trying to understand how autoimmune T cells and suppressive regulatory T cells navigate these conditions to persist or fail.
Members of my laboratory utilize genetically modified mouse models, multi-color flow cytometry, high resolution and 2-photon live imaging, single cell transcriptomics and epigenetic profiling to study autoimmune and regulatory T cell function. We have made several key observations regarding the function of Foxp3+ T cells in the context of autoimmune type 1 diabetes. Foxp3+ regulatory T cells employ multiple mechanisms to maintain immune and metabolic homeostasis, suppress autoimmunity, and aid in tissue repair. T cell receptor signaling and cellular interactions with tissue and effector T cells converge to guide Treg functions that are specialized for the tissue site and inflammatory context. Current work in the lab is focused on how Tregs integrate T cell receptor signaling with tissue-derived cues to modulate their suppressive functional program. Additional projects are focused on transcriptional and epigenetic mechanisms associated with autoimmune T cell function, autoimmune T cell memory, and T cell exhaustion in chronic inflammation.
Current ongoing projects
T cell receptor activation and control of regulatory T cell function
Regulatory T cells (Tregs) exhibit a unique T cell receptor (TCR) repertoire and enhanced TCR signaling in vivo compared to conventional T cells. We are applying high-throughput TCR sequencing, expression of select TCRs in vivo, and high resolution microscopy to investigate unique characteristics of Treg-derived TCRs and their cell-intrinsic differences in downstream signaling.
Image by Yi Jing - dSTORM microcopy image of an activated T cell's TCR clustering
Suppressive mechanisms of Foxp3+ regulatory T cells in autoimmune diabetes
Tregs exhibit a number of suppressive functions, including secretion of immune suppressive and tissue repair molecules. We are investigating Treg functional sub-populations in autoimmune environment, signals that drive their functional specialization, and the role of these molecules in regulation of pancreatic autoimmunity.
Image created with BioRender.com
TCR-redirected regulatory T cell adoptive therapy
We are testing natural and mutated TCRs for their ability to recruit Tregs into the autoimmune tissue and impart optimal function on TCR-redirected Tregs.
Image by Yi Jing - CD4+ T cells (green) infiltrating pancreatic islet and targeting insulin-producing beta cells (magenta).
Mechanisms that control T cell persistence in autoimmune tissue
Autoimmune T cells appear to avoid negative regulation by inhibitory receptors to maintain function long-term and avoid T cell exhaustion. We are applying single cell transcriptomics, epigenetics, and in vivo models to determine the mechanisms important for long-term maintenance of autoimmune T cells.
Image by Denise Allard Trout - Single cell RNAseq analysis of tissue-infiltrating CD4+ T cells.