Research Projects

1. Aspect of biotransformation enzymes gene regulation-implication for pharmacotherapy and prediction drug-drug-interactions

Nuclear receptors (NRs) such as Pregnane X receptor (PXR), constitutive androstane receptor (CAR) and Aryl Hydrocarbon Receptor (AHR) are the most important ligand/xenobiotic-activated transcription factors responsible for both basal and inducible expression of genes involved in drug metabolism and detoxification. However, only little is known about the dynamics of cytochrome P450 enzymes regulation and about posttranscriptional regulation of these NRs by miRNAs. The aim of the research line is to examine dynamics in NRs and their target genes expression and molecular mechanisms behind. The project could describe novel mechanistic aspects of drug/xenobiotic-metabolizing enzymes regulation in human hepatocytes, temporal effects of nuclear receptors based on mathematical modelling and have important clinical implication for personalized pharmacotherapy.

The project is conducted in collaboration with Professor Stanislav Mičuda, PhD and Dr. Elfriede Friedmann (Department of Applied Mathematics, Faculty of Mathematics and Computer Sciences, Mathematikon, University Heidelberg) and Martin Lanzendörfer (Faculty of Sciences CU).

Aspect of biotransformation enzymes gene regulation-implication for pharmacotherapy and prediction drug-drug-interactions

2. Clinical pharmacy and pharmacogenetics

The aim of this project is to apply pharmacogenetics in personalized pharmacotherapy of patients suffering from rheumatoid arthritis. We mainly focus on the influence of polymorphisms in genes involved in folate and adenosine pathways and involved in pharmacokinetics of methotrexate.

The project is conducted in collaboration with Dr. Tomas Soukup, Faculty Hospital in Hradec Kralove and with Prof. Jiri Vlcek, Department of Clinical and Social Pharmacy.

Clinical pharmacy and pharmacogenetics

3. Novel ligands of nuclear receptors

In collaboration with Dr. Radim Nencka and Dr. Eva Kudova (Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague), we are developing and testing novel ligand for several nuclear receptors. In collaboration with colleagues from our faculty, we are also involved in the development of novel antituberculotic drugs (Dr. J. Roh, Prof. Hrabalek group). Candidate compounds are tested in collaboration with Dr. Karel Chalupský (Czech Centre for Phenogenomics) and Prof. Micuda (Medical Faculty CU).

Novel ligands of nuclear receptors

4. Novel formulation for the delivery of nuclear receptor ligands

We are developing novel nanoformulation for the delivery ligands of nuclear receptors into cells of immune system. APIs of interest are small molecules as well as proteomic and genomic prodicts. We focus on PLGA nanoparticles and lipid nanoformulations (liposomes, solid-lipid nanoparticles, SNEDS) based on cationic lipids.

Novel formulation for the delivery of nuclear receptor ligands

5. Novel cellular models for drug development

Primary human hepatocytes are recommended in the different stages of drug development. Limited availability of high-quality human hepatocytes, the interindividual variability in biotransformation enzymes activities, and the decrease in liver-specific functions in culture are serious limitations of the model. Therefore, the aim of the project is to generate genetically-engineered cellular models, cellular models based on iPSC stem cells or co-culture models for drug development or as a model for the therapy of liver diseases. In the project, we closely collaborate with Dr. Sabine Gerbail-Chaloin (INSERM U1183, Montpellier, Prof. Daujat group) and Magnus Ingeman-Sundber (Karolinska Institutet).

 

Last update: 17/6/2019

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