Head

Grzegorz Maria Popowicz

My primary research activity is drug discovery with focus on protein-protein interaction and new targets scouting. Protein-protein interactome offer enormous number of Protein-Protein Interactions (PPI) that can be used as therapeutic targets. The applicability of PPI targeting has been confirmed only recently. However, development of PPI modulators is difficult due to lack of substrates that can be used as a starting point for analog development and usually large interfaces with dispersed binding energies. PPI usually require compounds of unique chemical properties seldom found in contemporary screening libraries. I am using structure-based computational methods to identify PPIs modulators. With a help of fragment-based screening, NMR-based SAR evaluation and X-ray crystallography, I design molecules that can serve as a chemical probe to validate PPI therapeutic proof-of-concept and be optimized into drug candidates.

Further, my research interest includes:

  • Multicomponent ligand chemistry, computational synthesis design
  • Integration of fragment based and multicomponent approach
  • Employing transient, dynamic states of the interface to optimize ligands
  • Novel computational techniques in drug discovery
  • SAR by X-ray and NMR
  • Structural biology of the complexes

Short Resume

Previous positons held

08/2008 - 12/2012Senior Postdoctoral fellow Structural Biology Department (NMR) Max Planck Institute for Biochemistry, Martinsried Germany. Supervisors: Dr. Tad Holak, Prof. Robert Huber
01/2010 - 10/2015Chief  Scientific Officer Crystallography  (CSO) Rayaxon GmbH
01/2008 - 01/2010
Advisor to pharmaceutical companies Selvita (Krakow, Poland) and Adamed (Warszawa, Poland). Planning and help in realization of large-scale in silico screening campaigns.
01/2006 - 01/2008Postdoctoral scientist   Structural Biology Department (X-ray Max Planck Institute for Biochemistry, Martinsried, Germany. Supervisor: Dr. Tad Holak

 

Education

10/2002 - 01/2006

Dr. phil. nat. Crystallographic and NMR functional studies of proteins and protein-protein interactions. Supervisor: Prof. Robert Huber (Nobel Prize in Chemistry 1988); Technische Universität München, Fakultät für Chemie; date of doctoral certificate: 26.1.2006, (grade: very good). Research performed at Max Planck Institute for Biochemistry, Martinsried Germany

10/1997 - 06/2002Master of Science Medical Physics and Dosimetry. Thesis title: Construction of a solid-state screening assay for the detection of the phosphatase activity in human serum.  University of Applied Sciences (AGH), Krakow, Poland

 

Key, selected Publications

52 research papers including 1 publication in Science, 2 publications in Nature, 2 in PNAS and 2 in Angewandte Chemie Int. Ed. Works have been cited 1726 times (June 2018).

Web of Science H-factor: 25.

ResearcherID: G-4769-2017        ORCID iD:  0000-0003-2818-7498

  1. Dawidowski M, Emmanouilidis L, Kalel VC, Tripsianes K, Schorpp K, Hadian K, Kaiser M, Maeser P, Kolonko M, Tanghe S, Rodriguez A, Schliebs W, Erdmann* R, Sattler* M, and Popowicz* GM. Inhibitors of PEX14 disrupt protein import into glycosomes and kill Trypanosoma parasites. (2017) Science 355, 1416-1420.   doi:10.1126/science.aal1807 [Pubmed]
  2. Hennig J, Militti C, Popowicz GM, Wang I, Sonntag M, Geerlof A, Gabel F, Gebauer F,  Sattler M
    Structural basis for the assembly of the Sxl–UNR translation regulatory complex
    (2014) Nature, 515:287-90. doi: 10.1038/nature13693. [Pubmed]
  3. Baek S, Kutchukian PS, Verdine GL, Huber R, Holak TA, Lee KW, Popowicz GM. Structure of the stapled p53 peptide bound to Mdm2. (2012) J Am Chem Soc. 134:103-6. doi: 10.1021/ja2090367. [Pubmed]
  4. Mishra SK, Ammon T, Popowicz GM, Krajewski M, Nagel RJ, Ares M Jr, Holak TA, Jentsch S. Role of the ubiquitin-like protein Hub1 in splice-site usage and alternative splicing. (2011) Nature. 474:173-8. doi:10.1038/nature10143. [Pubmed]
  5. Popowicz GM, Czarna A, Wolf S, Wang K, Wang W, Dömling A, Holak TA. Structures of low molecular weight inhibitors bound to MDMX and MDM2 reveal new approaches for p53-MDMX/MDM2 antagonist drug discovery. (2010) Cell Cycle. 9:1104-11. [Pubmed]

Patents

  • PL387416. Marked peptides, methods of detection of substances that modulate impact of mdm2-p53 and/or mdmx-p53, and the kit intended for detection of modulating substances.
  • WO2016038045: pyrazolopyridine derivatives and their use in therapy

Recent funding

  • 2013 - HMGU Developmental Projects funding for Pex14 inhibitors project
  • 2014 - HMGU Developmental Project extension
  • Feb 2015 - Zentrales Innovationsprogramm Mittelstand (ZIM) – together with Priaxon AG for investigation of fragment integration in multicomponent chemistry
  • May 2015 – Horizon 2020 ITN program for training early stage researchers in structure-based drug discovery techniques together with Prof. M. Sattler.
  • Nov 2015 – Validation funding from Wellcome Trust, UK
  • Jul 2016 – HMGU Developmental Project funding for novel diabetes treatment
  • Dec 2017 BMBF – Target validation proposal (VICTORI) together with Dr. Meyer, TUM
  • Oct 2018 (expected start) – BMBF VIP+ (PEXMED) PEX14 inhibitors

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