MOLECULAR CONTROL
OF IMMUNE RESPONSE

doc. Mgr. Lukáš Kubala, Ph.D.

Research focus
Molecular control of immune response research team (MCIR) is focused on elucidation of molecular mechanisms underlying acute and chronic inflammatory processes and of therapeutic targets. We in­vestigate the role of hyaluronan in the course of healing and inflammatory processes. This will be used for the development of hyaluronan based pharmaceuticals and biomaterials in collaboration with biotech company Contipro. Secondly, our objective is to develop fluidic models to study the relationship between blood flow, vascular inflammation and vessel recanalization during ischemic stroke. The third objective is to evaluate the biological importance of different isoforms of adenylyl cyclases in collaboration with the Medicinal Chemistry research team.

Research objectives

• Identification of molecular mechanisms responsible for the development of endothelial dysfunction and tissue damage under conditions of acute and chronic inflammation including ischemic insults.

• Development of new anti-inflammatory drugs targeting cAMP signaling pathways, particularly specific isoforms of adenyl cylases.

• Identification of the regulatory role of phagocytes and their newly defined subpopulations in the course of acute and chronic inflammation.

Main partners • Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany.

• BioMEMS Resource Center, Harvard Medical School, USA.

• Contipro a.s., Dolní Dobrouč, Czech Republic

Offered services and expertise

• Testing of anti-inflammatory drugs in in vitro models and evaluation of their efficiency in a variety of preclinical animal models.

• Studies employing endothelial cell seeded microfluidic systems that mimic microvascular system.

• Testing biocompatibility and regenerative potential of new materials and compounds, in vitro and in vivo.

Top publications

  • KOLAROVA, H., KLINKE, A., KREMSEROVA, S., ADAM, M., PEKAROVA, M., BALDUS, S., EISERICH, J., KUBALA, L. Myeloperoxidase induces the priming of platelets. Free Radical Biology and Medicine. 2013, 61(April), 357-369.
  • ADAM, M., GAJDOVÁ, S., KOLÁŘOVÁ, H., KUBALA, L., LAU, D., GEISLER, A., RAVEKES, T., RUDOLPH, V., TSAO, P., BLANKENBER, S., BALDUS, S., KLINKE, A. Red blood cells serve as intravascular carriers of myeloperoxidase. Journal of Molecular and Cellular Cardiology. 2014, 74(September), 353-63.
  • AMBROZOVA, G., MARTISKOVA, H., KOUDELKA, A., RAVEKES, T., RUDOLPH, T., KLINKE, A., RUDOLPH, V., FREEMAN, B., WOODCOCK, S., KUBALA, L., PEKAROVÁ, M. Nitro-oleic acid modulates classical and regulatory activation of macrophages and their involvement in pro-fibrotic responses. Free Radical Biology and Medicine. 2016, 90(January), 252-260.
  • Ambrozova, G., Fidlerova, T., Verescakova, H., Koudelka, A., Rudolph, T.K., Woodcock, S.R., Freeman, B.A., Kubala, L., Pekarova, M. Nitro-oleic acid inhibits vascular endothelial inflammatory responses and the endothelial-mesenchymal transition. Biochimica et Biophysica Acta. 2016. [Epub ahead of print]
  • Kudová, J., Procházková, J., Vašiček, O., Perečko, T., Sedláčková, M., Pešl, M., Pacherník, J., Kubala, L.. HIF-1alpha Deficiency Attenuates the Cardiomyogenesis of Mouse Embryonic Stem Cells. PLoS One. 2016, 29, 11(6), e0158358.

Other selected results

  • Significance of phagocyte derived enzyme myeloperoxidase in the pathogenesis of vascular dysfunction and cardiovascular diseases.
  • Mechanisms of function and therapeutic use of nitro-fatty acids as cardioprotective and anti-inflammatory mediators.
  • Determination of effect of hypoxia on differentiation of embryonic stem cells and role of HIF signalling in cardiac differentiation and regeneration.