Research Group Cell Signaling and Chemical Biology

We are interested in deciphering novel mechanisms and cellular regulators of ferroptotic cell death as well as developing tools to precisely detect ferroptosis:

• We use small molecules with known mode of action (Chemical Biology approach) and CRISPR/RNAi technologies (Genetic approach) to identify cellular regulators controlling ferroptosis.
• We develop high-content-imaging tools together with Artificial Intelligence techniques to visualize and classify ferroptosis.

Our Research concentrates on the identification and characterization of new regulators of ubiquitin signaling pathways implicated in cell death pathways:  

• We investigate the functional contribution of E3 Ligases and deubiquitinases (DUBs) to cell death pathways, in particular ferroptosis.
• We utilize proteomics and yeast-2-hybrid screening to identify novel protein-protein interactions and networks in ubiquitin signaling pathways.
• We use target-based as well as high-content phenotypic screening approaches to identify small molecule modulators of ubiquitin signaling.

The Hadian lab interrogates biological systems with small molecules to develop novel therapies. In the past decade, we have initiated and collaborated on a number of drug development studies within the fields of autoimmunity, infectious disease, rare disease, cancer, and more. Several of these studies have yielded patents and are currently at different stages of the drug development pipeline.

In the following are few examples of the current drug development activities:

• The TRAF6-Ubc13 protein-protein-interaction inhibitors developed for the treatment of autoimmune diseases (Rheumatoid Arthritis, Psoriasis, and more) are currently in preclinical lead optimization—patents: WO/2018/050286 and WO/2019/180207
• The SARS-CoV-2 PL^pro inhibitor acriflavine is being optimized for clinical application against beta-coronaviruses—patent: WO/2022/129210
• Repurposing of cyclosporin-A as a molecular corrector of mutant ABCA3 may be used to treat genetically caused interstitial lung disease in children

We collaborate with researchers at the Center as well as national/international cooperation partners and custom-design screening assays for the identification of novel bioactive molecules. Here, a major focus is devoted to the development of phenotypic assays for high-content-screening (HCS) in order to better reflect the biology of the underlying disease state. We use machine learning techniques to analyze high-content images. We provide state-of-the-art equipment and screening techniques as well as oversee the in-house diversity and focused compound libraries.