Professor Andrzej Marek Brzozowski

01904 328265
Email: marek.brzozowski@york.ac.uk

Structural Endocrinology and Medicinal Chemistry

Research Summary

My main interest is in understanding of molecular bases of hormonal signaling that are at the cross-section of metabolism, growth (cancer) and life-span control.  Human insulin, and its closely related Insulin-Like Growth Factors-I/II (IGF-I/II), governs these pathways, transducing signals through highly homologous Insulin and IGF Receptors (IR and IGF-1R). Current projects here include:

  • elucidation of insulin:IR interactions via structural studies of various insulin analogues and IR ectodomain fragments (i.e. 3-D description of the so-called site 1 and site 2 in insulin:IR complex);
  • development of a sustainable production of IR and IGF-1R fragments for structural studies;
  • development of novel insulin analogues and  its organo-mimetics for oral delivery of this hormone;
  • understanding of the structural bases for metabolic-mitogenic divergence between insulin and IGFs.

I also pursue application of structural biology to facilitate progress in tackling of the neglected diseases studying structure-function relationships in proteins important for vaccine development against Leishmania sp. and Chlamydia trachomatis.

Further information

Insulin receptor

Selected publications

  • How insulin engages its primary binding site on the insulin receptor.
    J G Menting, J Whittaker, M B Margetts, L J Whittaker, G K-W Kong, B J Smith, C W Watson, L Žáková, E Kletvíková, J Jiráček, D F Steiner, S J Chan, S.J.,  G G Dodson, A M Brzozowski, M W Weiss, C W Ward and M C Lawrence, Nature, 2013, 493, 241-245.
  • Design and Synthesis of Inhibitors of Plasmodium falciparum N-myristoyltransferase, a Promising Target for Anti-Malarial Drug Discovery.
    Z Yu, J Brannigan, D Moss, A M Brzozowski, A J Wilkinson, A Holder, E Tate and R J Leatherbarrow, Medicinal Chemistry, 2012, 55, 8879-8890.
  • Insulin and Insulin-like Growth Factor II Differentially Regulate Endocytic Sorting and Stability of Insulin Receptor Isoform A.
    A Morcavallo, M Genua, A Palummo, E Kletvikova, J Jiracek, A M Brzozowski, R V Iozzo, A Belfiore and A J Morrione, J Biol  Chem, 2012, 287,  11422-11436.
  • Non-equivalent role of inter- and intra-molecular hydrogen bonds in the insulin dimer interface.  
    E Antolíková, L Žáková, J P  Turkenburg, C W Watson, I Hančlová, M Šanda, A Cooper, T Kraus, A M  Brzozowski  and J Jiráček, J Biol Chem, 2011, 286, 36968-36977.
  • Directed epitope delivery across the Escherichia coli outer membrane through the porin OmpF.
    N G Housden, J A Wojdyla, J Korczynska, I Grishkovskaya, N Kirkpatrick, A M  Brzozowski and C Kleanthous, Proc Natl Acad Sci (USA), 2010, 107, 21412-21417.

Biography

A M Brzozowski received his PhD from the University of Lódz, Poland in 1980, with post-doctoral research in Max-Planck-Institut für Experimentelle Medizin (Göttingen, Germany) and the Department of Chemistry, University of York. After further work in York as Research Fellow and Reader, he was made a Professor of the University of York in 2013.  His works span a very broad field of structural biology, from biotechnology and health care enzymes, nuclear receptors to insulin-related hormonal regulation of human homeostasis and disease.