Our Mission

Large-scale genetic studies have succeeded in identifying thousands of associations between genetic loci and obesity, type 2 diabetes and other cardiometabolic traits in humans. Yet, the next grand challenge — dissecting the molecular and cellular mechanisms by which these variants affect disease (Variant-to-Function, V2F) — has yet to be solved and requires being able to determine the effect of genetic variants on molecular and cellular programs. The Claussnitzer lab has pioneered a principled V2F framework for going from genetic variants to genes to cells to biological pathways to provide actionable therapeutic hypotheses, first for the strongest genetic association with obesity, the FTO obesity risk locus (NEJM 2015). The Claussnitzer lab has further shown that this V2F framework generalizes to other genetic risk loci (Cell 2014, Biochim Biophys Acta Gene Regul Mech. 2020, Cell Metabol. 2021, Nat Commun. 2020, Sci Adv. 2021, Science 2021, Nat Genet. 2022, Nat Metabol. 2023).

The goal of our lab

While V2F studies help us to learn useful functional insights for metabolic disease, the one-locus-at-a-time approaches are currently not scalable, and it would take us decades to unlock the mechanisms encoded by the 1000s of genetic risk loci for metabolic disease.

The long-term goal of the Claussnitzer lab is to pioneer scalable V2F strategies to systematically unlock the consequences of genetic metabolic risk variation at the molecular and cellular level using adipocytes as model systems. To achieve this, the Claussnitzer lab develops and applies high-dimensional molecular and cellular profiling techniques to large-scale natural genetic variation screens and CRISPR perturbation screens to generate a foundational data set that will allow to systematically link genetic variants (V) to regulatory elements (RE) to genes (G) to morphological and cellular functions (M/F) in disease across adipocyte cell state transitions. Adipocytes are the ideal model system for modeling V2F effects and learning fundamental rules of genetic networks since they play a major role in the pathogenesis of metabolic disease and undergo substantial remodeling at the regulatory and cellular level over the course of differentiation and in response to metabolic stimuli.