Lisi Lab
Principal Investigator: George Lisi
Institution: Brown University (Providence, RI)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: ✅ Accepting PhD Students ✅ Hiring Postdocs
Research Focus
Project Summary Macrophage migration inhibitory factor (MIF) is critical to the pathophysiology of inflammation through its interaction with the chemokine receptor CD74, while also opposing the immunosuppressive effects of glucocorticoids and catalyzing enzymatic reactions of unknown biological significance. The mechanism by which MIF accommodates these and other biochemical functions within its compact structure is unclear, but we recently identified a network of amino acids that link the enzymatic active site of MIF with peripheral regions of the protein, including the proposed CD74 binding site. These residues, and likely others, allosterically regulate several biochemical functions of MIF, including enzyme catalysis, receptor activation, and protein-protein interaction. Preliminary data showed that multi-timescale dynamics of the MIF structure (and resulting changes to intersubunit hydrogen bonding) contribute to its function, leading us to hypothesize that intrinsic structural flexibility is a major driving force of the allosteric mechanism that enhances spatial-temporal control of MIF. The design of MIF selective inhibitors with therapeutic value for inflammatory diseases wou…
Active NIH Awards
- 5R01GM144451-05: Unraveling the Allosteric Mechanism of Macrophage Migration Inhibitory Factor with Molecular Resolution (2026)
- 5R01GM144451-04: Unraveling the Allosteric Mechanism of Macrophage Migration Inhibitory Factor with Molecular Resolution (2025)
- 5R01GM144451-03: Unraveling the Allosteric Mechanism of Macrophage Migration Inhibitory Factor with Molecular Resolution (2024)
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