Andrei Ursu, Ph.D. Email and Phone Number

Identification and mechanistic investigation of small molecule inducers of autophagy

Development of small molecule therapeutics targeting RNA in neurodegenerative disorders.Scientific supervisor: Prof. Dr. Matthew D. DisneyFunded by the German Research Foundation (DFG) and the Amyotrophic Lateral Sclerosis Association (ALSA).I am involved in all the aspects of de novo discovery of lead therapeutics to genetically defined c9ALS/FTD by targeting the RNA GGGGCC repeat expansions. This includes the development of high throughput screening assays, hit identification and validation as well as in-depth investigation of the RNA-ligand interaction using various biophysical techniques. In addition, I am applying various 1D and 2D NMR techniques together with computational tools to understand the structural changes of the RNA’s secondary structure upon small molecule binding. These in vitro studies were followed by rigorous assessment of mode of action studies in physiologically relevant c9ALS disease model systems using various target engagement techniques. Ultimately, our efforts led to the establishment of a drug discovery platform that has the potential to bring the therapeutic targeting of c9ALS/FTD with small molecules closer to in vivo testing.

Thesis title: "Development of small molecule modulators of stem cell reprogramming"Scientific supervisors: Professor Dr. Herbert Waldmann and Dr. Slava ZieglerEnrolled within the International Max Planck Research School in Chemical and Molecular Biology (IMPRS-CMB) graduate program and Faculty of Chemistry and Chemical Biology (Technical University Dortmund). I was involved in all aspects of chemical biology applied to phenotypic screening campaigns which include hit identification and validation, reaction methodology, library synthesis, structure-activity relationship (SAR) studies, chemical probe development, chemical proteomics, target identification and validation in vitro and in cellulis, mode of action studies, protein crystallization etc. These efforts have been applied in the case of two biologically relevant systems, namely efficient chemical reprogramming of partially differentiated stem cells to iPSCs and inhibition of Hedgehog signaling pathway. Our studies yielded two chemical probes, namely Epiblastin A (CSNK1 inhibitor) and Pipinib (PI4KIIIß inhibitor) that revealed interesting biology modulated by the small molecules.

Thesis title: "Design, synthesis and characterization of novel anion receptors"Scientific supervisor: Prof. Dr. Franz P. SchmidtchenFunded by the German Academic Exchange Service (DAAD).

Scientific supervisor: Prof. Dr. Franz P. Schmidtchen

Thesis titleScientific supervisors: