Radek graduated Engineering Science at University of Oxford and obtained his DPhil in Systems Approaches to Biomedical Science IDC at University of Oxford working on development of inhibitors for oxoglutarate dependent oxygenases at the Structural Genomics Consortium in the group of Prof. Udo Oppermann.
Before his DPhil, he was working on a LHC prototype at Oxford’s Physics Department, spent time at wind energy consultancy and also experienced a banking internship in the City.
The family of human iron- and 2-oxoglutarate - dependent oxygenases encompasses over 60 members and a subclass of the enzymes, containing Jumonji C (JmjC) domain, is directly involved in epigenetic control of gene transcription, through demethylation of methyl marks present on histone tails. Recently JmjC-type enzymes, namely MINA53, NO66 and OGFOD, were identified as ribosomal protein hydroxylases (ROXs) broadening the substrate set and indicating a function in the control of mRNA translation.
Oxygenases are frequently implicated as key regulatory factors in various types of cancers and targeted inhibition of this class of enzymes can lead to suppressed cancer cell proliferation, opening an epigenetic avenue for therapeutic intervention by small molecules.
In my DPhil I aimed to:
1. Characterise the family of JmjC- type oxygenases with a library of fragments in activity assays and X-ray fragment soaking in order to identify novel hit matter for further chemical optimisation.
2. Establish a platform for drug discovery for two poorly characterised ribosomal oxygenases NO66 and MINA53 consisting of activity assays and X-ray crystallography, and identify small molecule inhibitors of the proteins.
3. By using combined activity profiling and X-ray structural data collection, attempt development of active inhibitor molecules for members of the human JmjC- type oxygenases.
R. Nowak, et al. Hydroxamic acid inhibitors of JARID1B demethylase. 2016. Manuscript in preparation.
R. Nowak , et al. Active site characterisation across subfamilies of lysine demethylases and ribosomal hydroxylases using activity and X-ray fragment screening. 2016. Manuscript in preparation.
C. Johansson, S. Velupillai, A. Tumber, A. Szykowska, E. S. Hookway, R. P. Nowak, C. Strain-Damerell, C. Gileadi, M. Philpott, N. Burgess-Brown, N. Wu, J. Kopec, A. Nuzzi, H. Steuber, U. Egner, V. Badock, S. Munro, N. B. LaThangue, S. Westaway, J. Brown, N. Athanasou, R. Prinjha, P. E. Brennan and U. Oppermann. Structural analysis of human KDM5B guides histone demethylase inhibitor development. Nature Chemical Biology. 23 May 2016.
C. M. C. Lobley, J. Sandy, J. Sanchez-Weatherby, M. Mazzorana, T. Krojer, R. P. Nowak and T. L. Sorensen (2016). A generic protocol for protein crystal dehydration using the HC1b humidity controller. Acta Cryst. (2016). D72, 629-640
M. Korczynska, D. D. Le, N. Younger, E. Gregori-Puigjané, A. Tumber, T. Krojer, S. Velupillai, C. Gileadi, R. P. Nowak, E. Iwasa, S. B. Pollock, I. Ortiz Torres, U. Oppermann, B. K. Shoichet, and D. Galonić Fujimori (2015). Docking and Linking of Fragments to Discover Jumonji Histone Demethylase Inhibitors. Journal of Medicinal Chemistry
A. J. Connor, R. P. Nowak, E. Lorenzon, M. Thomas, F. Herting, S. Hoert, T. Quaiser, E. Shochat, J. Pitt-Francis, J. Cooper, P. K. Maini, H. M. Byrne (2015). An integrated approach to quantitative modelling in angiogenesis research. Journal of The Royal Society Interface, 12(110), 20150546.
W. Aik, R. Chowdhury, I. J. Clifton, R. J. Hopkinson, T. Leissing, M. A. McDonough, R. Nowak, C. J. Schofield, L. J. Walport (2015). Introduction to Structural Studies on 2-Oxoglutarate-Dependent Oxygenases and Related Enzymes. RSC Metallobiology. 10.1039/9781782621959-00059.
C. Johansson, A. Tumber, K. Che, P. Cain, R. Nowak, C. Gileadi, & U. Oppermann (2014). The roles of Jumonji-type oxygenases in human disease.Epigenomics, 6(1), 89–120.
20-21 April 2016, Cambridge Healthtech Institute’s Fragment Based Drug Discovery meeting, San Diego, US
Talk title: X-ray and Activity Fragment Screening across Subfamilies of Lysine Demethylases and Ribosomal Hydroxylases for Active-site Characterization
Aug. 2014, CCP4 Northern Crystallography Meeting, Carlisle, UK.
May 2014, Epigenetics Conference Oxford, Crystallography Workshop in Erice, Italy
Feb. 2013, Epigenetics Conference, Oxford, UK
2014. Santander Travel Award, Lady Margaret Hall, Oxford
2011. Awarded LMH Divisional Scholarship of £2000
2011. Distinction, MEng. Engineering Science, University of Oxford
Prof. Udo Oppermann, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford
Dr. Catrine Johansson, NDORMS, University of Oxford
Dr. Anthony Tumber, SGC, University of Oxford
Dr. Dafydd Owen, Pfizer, Boston, MA
Lady Margaret Hall, Norham Gardens, OX2 6QA, Oxford.
Email: radoslaw.nowak AT dtc.ox.ac.uk