Translational research

The Icahn School of Medicine at Mount Sinai (ISMMS) is part of the Mount Sinai hospital system in New York City, granting us unique access to large and diverse patient cohorts with a range of inflammatory conditions. Leveraging this clinical access and the collaborative environment of ISMMS with world-renowned physicians, we seek to define novel mechanisms underlying inflammatory diseases. Our approach is 'reverse translational': we first develop well-defined and interventional patient cohorts, then use high-dimensional profiling to understand cellular and molecular disease states. Using human organoids, tissue biopsy cultures, and murine preclinical models, we establish causal relationships between our identified targets and diseases, providing key proof-of-concept validation.

A successful example: We used cutting-edge spatial transcriptomics profiling to map emergent cellular ecosystems in a cohort of patients with psoriasis (Catillo, Sidhu et al Science Immunology 2023). In doing so, we identified epithelial HIF1α as a unique fingerprint of patients with psoriasis (Subudhi Konieczny et al. Immunity 2024). Using a 'trial in a dish' system with patient psoriatic lesions, we compared HIF1α inhibition to topical standard of care (SOC) and found that 1) HIF1α had a more dramatic and rapid molecular effect than SOC, and 2) HIF1α inhibition mimicked IL-17A inhibition, suggesting HIF1α as a promising new therapeutic target in psoriasis.

Our robust 'bedside to bench' platform positions us to collaborate with biotech and pharma to understand complex disease states and deliver high-quality, therapeutically actionable results.