FOXP3 and EZH2 binding in human Treg cells
Human T-regulatory (Treg) cells depict binding of enhancer of zeste homolog 2 (EZH2) and forkhead box protein 3 (FOXP3) via phospholipase A signaling in a proximity ligation assay (PLA) (pink dots). Source: Bamidele AO, Svingen PA, Sagstetter MR, Sarmento OF, Gonzalez M, Braga Neto MB, Kugathasan S, Lomberk G, Urrutia RA, Faubion WA. Disruption of FOXP3-EZH2 interaction represents a pathobiological mechanism in intestinal inflammation. Cellular and Molecular Gastroenterology and Hepatology. 2019.
Focus areas
Our lab's research focuses on:
- T-cell epigenetic programming. We investigate the chromatin-based mechanisms that govern T-cell differentiation and stability, with a focus on FOXP3-dependent regulatory programs and their disruption in inflammation.
- Immunometabolism and inflammatory signaling. We define how metabolic pathways intersect with epigenetic regulation to drive T-cell function and pathogenicity, including lipid metabolism and energetics in CD4+ T cells.
- Multi-omic and systems immunology. We use single-cell RNA-seq, ATAC-seq, ChIP-seq, and spatial platforms to resolve immune cell states in human tissue and model systems, integrating these datasets to identify regulatory networks.
- Therapeutic development. We develop strategies to manipulate immune cell state, including ex vivo T-regulatory (Treg) engineering, CRISPR-based approaches and targeting of epigenetic regulators with small molecules.
So far, the lab has:
- Identified epigenetic regulators such as G9a or BMI1 that control metabolic and inflammatory programs in T cells.
- Defined pro-inflammatory FOXP3+ T-cell states as a targetable mechanism in inflammatory bowel disease.
- Demonstrated that metabolic reprogramming is a key driver of chronic intestinal inflammation.