Expertise
1) The discovery that IL-2 is essential for the development and function of regulatory T cells, essential cells that maintain immune tolerance. This was a paradigm shift in the field by redefining IL-2 from a molecule important for immunity to one that is indispensable and central for suppression of autoreactive T cells.
2) The discovery in preclinical models that low levels of IL-2 receptor signaling effectively support key activities of regulatory T cells but not effector and autoreactive T lymphocytes. This finding is a major underpinning for the current investigation of low-dose IL-2 in patients with autoimmunity, including type 1 diabetes, at the DRI and by other investigators around the world.
3) The discovery with Alberto Pugliese, M.D., that quantified a precise therapeutic window in human lymphocytes for the selective response of regulatory T cells to low-dose IL-2. This work provides a pharmacological basis that further highlights the promise of low-dose IL-2 as an agent to boost regulatory T cells in autoimmune diseases.
4) The discovery of a novel variant of IL-2 that is much longer-lasting and more effective than recombinant IL-2 in expanding autoimmune-suppressive regulatory T cells. This molecule is currently being developed by a major pharmaceutical company for clinical trials.
One major aspect of our current research is to better define the mechanisms by which regulatory T cells (Tregs) contribute to self-tolerance, with a focus on the role of IL-2R signaling.