Academy of Finland funds five new Postdoctoral Researchers at the UEF

The Academy of Finland’s Research Council for Health has decided to fund five new Postdoctoral Researchers at the University of Eastern Finland. Their research topics vary from Alzheimer’s disease and autoimmune diseases to cell reprogramming and novel therapies to treat cardiovascular diseases.

Postdoctoral Researcher funding is designed to advance the professional competence and independence of promising researchers. Postdoctoral Researchers are appointed for three years.

The aim of Postdoctoral Researcher Kati-Sisko Vellonen’s research is to clarify the effect of Alzheimer’s disease on the delivery of drugs. Alzheimer’s disease is the most significant cause of dementia in the world and its prevalence will increase in the future due to the aging of the population. The blood-brain barrier (BBB) functions as a selective fence protecting the central nervous system (CNS), but its function may be weakened in the neurodegenerative disorders, such as Alzheimer‘s disease. This may cause substantial changes to the entry of drugs into the brain, to the therapeutic effect and also to the risk of adverse effects. The aim of the study is to clarify how Alzheimer’s disease affects BBB permeability, delivery of drugs to the CNS and their regional distribution in the brain. In addition, the expression of drug transporters in the BBB will be investigated. The influence of Alzheimer’s disease on brain pharmacokinetics will be evaluated and predicted with a simulation model.

Postdoctoral Researcher Irina Gureviciene’s research focuses on the functional role of amyloid plaques in the pathogenesis of Alzheimer’s disease. Pathologically Alzheimer’s disease (AD) is characterized by amyloid plaques that consist of an A-beta (Ab) peptide. However, most studies have failed to find a correlation between plaque load in AD patients’ brains and cognitive performance. On the other hand, levels of soluble toxic Ab species, called oligomers, in patients’ brains correlate much better with cognitive decline. Therefore, amyloid plaques may be the result of the neuron attempt to get rid of Ab oligomers. These hypotheses will be tested by using a transgenic mouse model of AD that develops amyloid plaques and memory impairment with increasing age.

Autoimmune diseases are a major health problem worldwide. Together there are over 80 types of autoimmune diseases, which are typically treated with non-specific immunosuppression that causes a wide range of side-effects. Perforin is one of the main components found in the destruction of specific cells in autoimmune diseases. Function of perforin can be inhibited, which makes it as a potential drug target. The aim of Postdoctoral Researcher Kristiina Huttunen’s research is to develop novel prodrugs to target perforin inhibitors selectively to the granules where perforin is stored, and across the blood-brain barrier to improve medication of infectious central nervous system diseases.

Progression of atherosclerosis arises from interplay between macrophages, endothelial cells and smooth muscle cells that influence each other and modify the microenvironment of the plaque. However, little is yet known of the interactions between these cells. In the first part of their study, Postdoctoral Researcher Minna Kaikkonen and colleagues aim at revealing the transcriptional and functional responses of these cells to inflammatory stimuli and hypoxia using next generation sequencing methods. Stimulating revascularization is an attractive strategy to treat ischemia in patients with advanced atherosclerosis. However, none of the existing therapeutic approaches have shown sufficient efficacy. The second part of the study aims at characterizing changes in the transcriptional and post-transcriptional regulation of mRNAs in the context of hypoxia and therapeutic angiogenesis. Finally, the study wishes to identify non-coding RNAs exhibiting global changes during atherogenesis and angiogenesis and characterize their role in these processes.

Postdoctoral Researcher Jonna Koponen’s project focuses on methods of producing blood vessel endothelial cells for cell therapies of cardiovascular diseases and studying the therapeutic potential of these cells in pig models of myocardial ischemia and coronary artery stenting. Endothelial cells will be produced via novel reprogramming technology based on the expression of specific transcription factors in fibroblasts. Reprogramming methodologies aiming at the creation of induced pluripotent stem cells capable of differentiation into endothelial cells and direct reprogramming of fibroblasts to endothelial cells will be utilized. In addition, endothelial cells will be modified with gene transfer vectors to secrete therapeutic molecules in the target tissue.

For further information, please contact:

Science Adviser Heikki Vilen, Academy of Finland, tel. (09) 7748 8456, heikki.vilen(at)aka.fi

Publishing year: 2012

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