Tomasz Cierpicki

Research Focus: Structural biology, Development of small molecules targeting protein-protein interactions, Development of NMR techniques for drug discovery

The research in Dr Cierpicki’s laboratory is focused on structural and functional biology of leukemia related proteins.  We are interested in understanding the molecular basis leading to acute leukemia and in development of small molecules which could reverse the effect of leukemia oncoproteins. One of the current projects in my laboratory is dedicated to determine three dimensional structure of menin and to understand menin interaction with MLL-fusion oncoproteins. We are using broad range of biochemical, biophysical and structural biology methods (NMR and X-ray crystallography) to characterize the interactions of menin with MLL, LEDGF, c-MYB and other physiological partners which are relevant to MLL leukemias. In collaboration with Dr. Jolanta Grembecka we are developing small molecules targeting various menin interactions essential for leukemogenesis to reverse the oncogenic potential of MLL fusion oncoproteins.

In parallel projects we are also employing NMR methodology to facilitate development of small molecule inhibitors of protein-protein interactions for targeted therapies in cancer. For this purpose we are applying fragment-based screening approach, measurements of inter-ligand NOEs to design bidentate compounds and Inpharma technique for pharmacophore mapping. We are also developing an approach to experimentally assess druggability of protein targets. Laboratory of Dr. Cierpicki is equipped in state-of-the art NMR spectrometer with automatic sample changer allowing for programmed running of NMR experiments as well as in robotic system for automatic sample preparation. Our goal is to develop small molecule inhibitors of several proteins with well established role in various cancers, including IBD domain of LEDGF, protein phosphatase CDC25B, BMI-1 E3 ligase.