Projects / Programmes
Pharmacology and pharmacogenomics
January 1, 2014
- December 31, 2017
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| Code |
Science |
Field |
| B740 |
Biomedical sciences |
Pharmacological sciences, pharmacognosy, pharmacy, toxicology |
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
Researchers (28)
Organisations (2)
Abstract
Research program P3-067 connects two complementary areas: pharmacology and pharmacogenomics.
In the pharmacological part of the research program P3-067 Pharmacology and Pharmacogenomics will continue to research biogenic amine histamine: its release from mast cells under the influence of non-steroidal anti-inflammatory drugs; histamine binding to the histamine H2 receptor subtype and the role of intermolecular forces in this process; histamine uptake via transporter(s) in endothelial and glial cells and the nature of this process; and degradation of histamine and other amines with different enzymes. This part of the research will be performed on isolated cells, primary cell cultures, isolated rat and guinea pig organs, and whole test animals.
We plan to extend the research, which we have become possible in the time period 2009-2013. We will study the functional changes of drug action sites (receptors, enzymes, transporters); cell viability , forms of cell death and the consequences of cell damage caused by oxidative stress and exposure to natural toxins. We will continue also with the discovery of biomarkers of cancer and degenerative diseases in human body fluids.
In our previous pharmacogenomic studies we have generated comprehensive biobank of DNA, RNA, protein and serum samples from clinically well characterized patients blood and tissue samples. Our biobank include more than 600 Inflammatory bowel disease (IBD) patients (1200 RNA samples taken during adalimumab therapy), 500 asthma patients (800 RNA smples taken during treatment with antileukotriens and corticosteroids), 250 rheumatoid arthritis, 250 osteoarthritis and 250 patients with multiple sclerosis. So far, we have identified many single nucleotide polymorphism associated with diseases, however surprisingly most of disease SNPs were located in non-coding regions.
The aim of our study is to perform post GWAs study, specifically, to link non-coding disease associated SNPs to genes they affect, to identify causal SNPs and to explain molecular mechanism how non-coding SNPs affect genes and proteins involved in disease pathogenesis of common chronic immune diseases. In addition we will correlate genotype and gene expression data to clinical data, including treatment outcome data, for discovery of biomarkers for personalized medicine. Initially we will focus on inflammatory bowel disease, a typical complex disease which has been most widely studied using GWAs analysis and asthma, the most common disease in childhood. In addition, study of related immune diseases, rheumatoid arthritis, osteoarthritis and multiple sclerosis allows us to compare genetic structure between diseases and identify common molecular pathways involved in common immune diseases.
Significance for science
Programme group connects two complementary areas - pharmacology and pharmacogenomics that enables faster development of the two fields and consequently a faster development of new drugs, biologics, new diagnostic tools and treatments.
Pharmacology:
The results of the research program will explain the effects and mechanisms of action of endogenous and exogenous substances investigated: neurotransmitters (eg, histamine), immunomodulators (histamine, cytokines) and toxins (melitin, ethanol) on the human body in various states and physiological or pathophysiological conditions. Some of the results will be demonstrating new applications of known pharmacologically active substances in clinical practice (non-steroidal anti-inflammatory drugs, psychotropic medication), the other on the possibility of developing new drugs to a specific, desired effect (nootropiki).
Interdisciplinary integration of pharmacology and pharmacogenomics is a new value-added performance and research results in both fields. A significant part of the pharmacological research focuses on the study sites of drug action in the central nervous system and drugs that affect the central nervous system (psychoactive drugs nootropiki), which is in line with European research priority "Brain Research.
Pharmacogenomics:
The most interesting results of the analysis of the links between genotype, gene expression and clinical data expected in prospective pharmacogenomic study in patients with Crohn's disease who are involved in treatment with the biologic drug adalimumab based on monoclonal antibodies against pro-inflammatory cytokine TNF-?. The discovery of new pharmacogenetic biomarkers are expected to prospective pharmacogenomic study in patients with childhood asthma who are involved in treatment with corticosteroids and anti-leukotrienes.
The first study, which will link genotypes obtained using microarray technology (microarrays) for the post GWA with extensive clinical data, including identification of the main subtypes of asthma (atopic and nonatopic); The first comprehensive eQTL analysis in blood lymphocytes and tissues of patients with chronic immune-mediated diseases with which we discover new eQTL loci and non-coding polymorphisms associate with new genes that previously have not yet been associated with chronic immune-mediated diseases. In the best of our knowledge, our biobanks in svetovenem scale one of the largest biobank of chronic immune disease, which contain all pairs of DNA / RNA samples isolated from the same patient in the course of therapy, which gives us a distinct advantage for the post GWA studies, particularly for statistically strong eQTL studies. The discovery of causal polymorphisms and their links to the actual pathological genes will greatly facilitate the further functional studies and the development of biomarkers and predictive models for personalized medicine
Significance for the country
In Slovenia and EU, it is important that we maintain and develop a research work at the university and educate the younger staff that will be able to work innovatively and understanding of scientific achievements in the world.
With the development of new (and more expensive) drugs pharmacological knowledge is becoming increasingly important in the introduction, use and financing medicinal products. Trained personnel in the field of pharmacology in Slovenia are also important for the contribution in the authorisation and pharmacovigilance procedures in the European Union. Innovative and highly trained staff can contribute to the efficient administration, market competitiveness of the industry and the development of university education itself.
Researching centrally acting drugs is one of the main strategies in Western world. Due to better living conditions, and available health a significantly longer life expectancy is expected and will result in the increased number of people suffering from neurodegenerative diseases. The appropriate pharmacotherapy can slow the progression of neurodegenerative process and enables elderly to live independently.
With the introduction of new drugs in Slovenia is necessary to know the basics of pharmacological actions of new drugs for rational pharmacotherapy., The results of pharmacogenomic studies enable the introduction of a more personal treatment with drugs. Fewer adverse drug effects and lower costs are also expected..
Greater added value can be expected after formation of spin-off companies that will deal with the development of pharmacogenomic diagnostic products.
Most important scientific results
Annual report
2014,
2015,
2016,
final report
Most important socioeconomically and culturally relevant results
Annual report
2014,
2015,
2016,
final report
