Research portfolio

Our research group investigate different potential diagnostic, therapeutic possibilities and the clinical/functional outcome in case of traumatic brain injury (TBI) applying translational research strategies:

• Clinical studies in TBI:

Beside coordinating the collection of biological samples (serum, plasma, cerebrospinal fluid) from patients with head injury and other central nervous system disorders, as well as the professional long-term storage of these samples, identification and measurement of the levels of protein biomarker molecules with diagnostic and prognostic potential for TBI, and perform complex analysis of the results in the light of other clinical patient data.

In the case of the so-called CENTER-TBI ("Collaborative European NeuroTrauma Effectiveness Research in TBI") project - funded by the FP7 mechanism of the European Union – the biomarkers were measured from serum samples collected from more than 3500 head injury patients from more than 50 sites across Europe between 2013 and 2021 with the participation of our Research Group – complex analysis and publication of the collected clinical and biomarker data is currently underway.

The maintenance of the "Pécs Severe Head Injury Database", (which was started in the summer of 2002 and contains clinical data of more than 700 severe head injury patients treated at the Neurosurgery Clinic of the University of Pécs) and the statistical analysis of the collected data for various purposes as well as publication of the results.

• Experimental neurotraumatotlogy:

Investigation of traumatic brain injury (TBI) with the utilization of our two licensed neurotrauma animal models: a) the impact acceleration head injury model – described by Marmarou et al. 1994 – and b) the fluid percussion head injury model – described first (for rats) by Dixon et al. 1987. Quantification of the impact of the injury – in strong collaboration with many other research groups of the Centre – involve histological methods (immunohistochemistry; silver staining methods), functional tests, measurement of protein biomarker levels as well as neuro-imaging (MRI, microCT) techniques. Investigation of histological, blood based biomarker and functional alterations – as a consequence of mild/repetitive mild TBI – represent the main focus of our recent experiments.

1. Retinal electrical synapses team: Prof. Dr. Béla Völgyi, Dr. Tamás Kovács-Öller, Gergely Szarka, Márton Balogh, Boglarka Balogh

Over 85% of the information perceived by our nervous system is processed by the retina, thus it is essential to understand how the retinal neuronal hyper-network works. Electrical synapses have been known for some 40 years, however their crucial role in visual information processing has only become obvious in recent years. Our team performs experiments to show that electrically coupled retinal neuronal networks play important roles in higher visual functions. We examine the expressional changes of the gap junction forming connexin proteins during the postnatal development and/or induced by changes in the environment. Our work particularly focuses on those inner retinal gap junctions that are formed by ganglion and amacrine cells (ganglion-ganglion, amacrine-amacrine and amacrine-ganglion) and participate in the synchronization of ganglion cell action potentials. We study how such ganglion cell population activity encodes certain visual patterns or visual cues. We also study how the function of electrical and chemical synapses affect each other and if they interfere and/or cooperate to serve signaling. Results of our research will contribute to algorithms for the stimulation of retinal prostheses and/or to provide data to design high performance bionic eyes for robotics.

Alumni: Dr. Ádám Tengölics, László Albert, Gábor Debertin PhD, Anikó Óhidi-Légmán, Erica Popovich, Adrienn Szabó, Dániel Varga

2. Retinal signalization team: Prof. Dr. Róbert Gábriel, Dr. Andrea Kovács-Valasek, Dr. Alma Ganczer

Our research focus is to expand our knowledge on the mechanisms of metabolic retinal degenerations by exploiting experimental work with animal models. We explore how metabolic mechanisms that mediate human retinal degenerations induce retinal cell loss, and which biochemical signaling pathways are involved in mechanisms that eventually impair vision. Our results will reveal the potential rescue mechanisms to avoid retinal degeneration by blocking the degeneration pathways or by enhancing mechanisms that serve neuronal protection. The knowledge on this latter issue will allow us to test and design new pharmacological compounds. Throughout these experiments we will also gain information on the mechanisms of retinal information processing, neuronal degeneration and neuronal protection.

Studying stress-induced structural and functional alterations in animal models for neuropsychiatric disorders

The physiological stress response is essential for our daily survival and helps us to adapt to the ever changing environment. However, sustained uncontrollable stress can induce various dysfunctions and pathological alterations in our body. Our key interest is the structural plasticity of the brain in relation to stress.

We focus on stress-induced changes in neuronal plasticity affecting neuronal networks, adult neurogenesis as well as glial changes in the hippocampus and neocortex. We hypothesize that such stress-induced structural changes contribute to the pathophysiology of psychiatric disorders like depression or schizophrenia, but medications like antidepressant, antipsychotic treatment can also have influence. 

We aim for translational research using multidisciplinary methods ranging from molecular biology to in vitro and in vivo imaging.

The Translational Neuroscience Research Group was establish by István Hernádi, PhD in 2012 at the University of Pécs. The research group develops preclinical models of neurocognitive disorders in four laboratories:

1. Small animal behavior laboratory: general activity, open field test, elevated plus maze test, forced swim test, food-choice tests, computer controlled operant behavioral chambers, neurotoxic brain lesions, reversible brain inactivation, central/systemic administration of bioactive agents.

2. In vivo cellular laboratory: extracellular unit recording, stereotaxic apparatus, biollogical signal conditioning (amplifiers,filters, ADCs, measurement of voltage and current), constant current ganerators (for microiontophoresis).

3. NHP research laboratory at the Grastyán Endre Translational Research Centre

4. Human psychophysiology laboratory: high performance 32 channel biological amplifier (EEG, EMG, ECG, EOG), computer controlled behavioral apparatus. Current research 1) basic: neurophysiology of face perception; 2) applied: neurocognitve effects of non-ionising environmental electromagnetic fields.

The research group is dedicated to basic and applied research in systems neuroscience. We aim to adopt and further develop in vivo animal and human models of higher order mammalian brain function with special emphasis on searching functional biomarkers of pathological mechanisms related to neurodegenerative brain disorders, esp. Alzheimer's disease, schizophrenia and developmental spectrum disorders. The four laboratories provide a unique repertoire of technical tools for targeting multidisciplinary research within the same research group. Our main objective is to support the need of parallel comprehensive testing of novel drug-candidates against cognitive impairment in in vivo preclinical animal experiments and human studies.

The most important research topic of our research group is heart failure, which is the only cardiovascular disease with an increasing incidence. Heart failure is a disease characterised by poor prognosis and its mortality has not significantly reduced despite the numerous therapeutic possibilities. We also investigate the therapeutic approaches of other pathologies leading to heart failure, for example/such as myocardial infarction, hypertension and atrial fibrillation.  

We are studying the role of the interplay between certain signaling factors and mitochondrial quality control in these pathological progressions. In addition, we are seeking to find possible therapeutic targets along this axis. 

Based on research in recent years, the PARP enzyme is one of the most promising targets in both the prevention of heart failure and the treatment of established disease. PARP-inhibitors besides their “orthodox” NAD+-preserving effect, can also influence several signal transduction pathways. They have a direct mitochondrial protective effect, preserve the activity of the components of the respiratory chain, have a positive effect on the activity of signaling factors, thereby reducing the process of cardiovascular connective tissue remodeling.  

An other promising path is the pharmacological modulation of the mitochondrial quality control. We are conducting experiments on the inhibition of fission, promoting fusion processes and enhanced the mitochondrial biogenesis, thus uncovering the role of the above mentioned processes on the development of heart failure.  
 

The research team's results focus on the application of novel bioimpedance-based technologies:

• development, verification, modelling and validation of in vitro measurement cells with different dedicated electrode architectures (for spectroscopy and tomography applications),
• identification (calibration and validation) of basic cell biological processes (proliferation, apoptosis, necrosis, hypertrophy, etc.) using bioimpedance measurements,
• monitoring the mechanisms of action of chemotherapy using the above tools and results,
• monitoring the mechanisms of action of non-alcoholic fatty liver disease (steatosis and fat accumulation) by in vitro bioimpedance spectroscopy and by the above tools and results,
• monitoring the response of bacterial cultures to different treatments using the above tools and results,
• the use of microfluidic systems, with continuously optimized measurement set-ups, electrode configurations and even routine experiments on different cell lines and mouse embryos.

During our activities, the manufacturing properties (in particular reproducibility) and biocompatibility of our in vitro measuring cells will be verified, and in the first in vitro experiments using HepG2 cell lines, the development of steatosis will be monitored and the characteristics of fat accumulation will be correlated with the parameters obtained from bioimpedance measurements. Furthermore, the possibility to maintain bacterial cultures in our in vitro measuring cell in such a way that bioimpedance monitoring can be routinely performed on them will be investigated.
In addition, microfluidic systems are being designed to bring a new basis to our in vitro measurements. For these measuring chips, gold and platinum electrode configurations in different geometries are developed. Moreover, their metrological, biocompatibility and mechanical properties are being investigated. Of course, the behaviour of microfluidic chips is modelled using finite element and a mathematical method developed by the group.

Collaborating partners:

NWM Consult Ltd.
PTE ÁOK Institute of Physiology
PTE MIK Symbolic Methods in Material Analysis and Tomography Research Group
PTE ÁOK Institute of Medical Microbiology and Immunology
HUN-REN Energy Research Centre Institute of Physics and Materials Engineering Microsystems Laboratory
HUN-REN Institute of Enzymology, Research Group Drug Resistance

1. On the one hand, we target the replication cycle of the virus with RNA interference gene silencing. This method has been successfully applied for many viral infections. The primary goal of RNA interference is the evolutional protection against exogenous pathogens and harmful, endogenous nucleic acids. The RNA interference is generated by double-stranded RNA molecules, which can specifically attach to complement mRNA sequences, and by that leading to gene-specific translational silencing. Synthetic siRNA molecules designed by our group are evoking posttranscriptional silencing, when endonucleases degrade the target mRNAs.
2. The other in-cell approach aims to hinder the assembly of the viral capsid with the application of specific, synthetic peptides. The interfacial attachment of low molecular weight peptides are blocking one or more “hotspots” on the surface of the given protein, thus confounds the viral capsid assembly through competitive interactions with other viral proteins.

1. Whilst many studies are focusing on this subject in Europe, data on the situation in Central-Eastern Europe and in Hungary is rarely available. Regular monitoring of bats can give us information on the distribution of viruses in time and space. Furthermore it enables the examination of the most common genetic variants.
2. The successfulness of virus isolation from different animal and human cell lines can give us information about their zoonotic potential.
3. The results of virus isolation experiments from primary cell lines and immortalized cell lines are highly important, because it enables us to establish an applied laboratory model and it also gives an opportunity to study the chiroptera-borne viruses virus-host interactions. These data could give an essential insight to further investigate pathomechanisms and lay ground for clinical studies.

Our research group focuses on the involvement of Wnt signaling in the ageing process of the lungs and the thymus. Wnt signaling plays a pivotal role in physiological aging as well as in age-associated diseases including cancer formation and inflammation.

• Applied Environmental and Geoscience Research; Geoenergy; GeoResources; Renewable Energy; Raw material Research
• Liquid chromatography, gas chromatography, capillary and microchip electrophoresis, mass spectrometry, sample preparation
• Study of environmental contaminants and microorganisms interactions. Biosorption and biodegradation. Bioanalysis
• Geomicrobiology and Biogeochemistry
• Environmental Geology, Sedimentology
• Sedimentary petrography
• Water-rock interactions
• Mineralogy

Generation and application of terahertz (THz) pulses with high pulse energy, and with extremely high electric field strength that is sufficient for nonlinear THz spectroscopy applications. Searching for new application possibilities in the fields of material-, medical-, and life sciences.

Manipulation, acceleration, focusing and temporal shaping of electrically charged particle bunches (electrons, protons, ions) with THz pulses having extremely large electric field strength. Elaboration of the theory of a possible table-top proton accelerator making possible the use of protons having low energy for hadron therapy applications. Generation of single cycle UV and X-ray radiation with Thomson scattering.

In the frame of ELI (Extreme Light Infrastructure) generation of attosecond light pulses with the method of THz assisted high harmonic generation.

Our results as far as here: Presentation of optimal parameters for design of tilted pulse-front based THz generator scheme. It was shown that in case of using longer wavelength than the typical 800 nm in a tilted pulse-front excitation scheme semiconductors (like ZnTe, GaP) are competitive with LiNbO3 from the point of view of efficiency. It was shown, that in case of LiNbO3 the peak THz electric field strength can be increased by more than one order of magnitude using ~500 fs pump pulse length, and cryogenic temperature. With this technique it is possible to generate single cycle THz pulses with pulse energy exceeding 10 mJ, and with peak electric field strength of 100 MV/cm with central frequency about 1 THz.

The research field of the team is the developmental biology of murine lymphoid tissues involved in immune defence, addressing the roles of hematopoietic and stromal constituents. We have produced several rat monoclonal antibodies against the cellular and matrix components of mesenchymal scaffolding, for evaluating the roles of various morphogenic factors (DNA-binding proteins and cytokines) guiding the development of spleen and intestinal lymphoid tissues in animal experimentations by using transgenic models and in vivo immunomodulatory approaches. In this work, we have identified hitherto unknown lymphoid tissue components and novel forms of lymphoid tissues, which may play important roles in the regulation of peritoneal lymphocyte distribution and progression of lymphoid malignancies. 

Our R&D activities cover the analysis of immunomodulatory agents affecting the structure, composition and immunological functions of lymphoid organs, and the development of tumor models; recently we have initiated recombinant antibody development. The service portfolio includes the development of monoclonal antibodies (rat and mouse), immunochemical procedures (antibody purification and downstream processing, labelling [fluorochromes, biotin, HRPO], QC), fluorescence, immunohistochemical and serological kit development and lymphoid tissue analysis, cell sorting (fluorescent and magnetic), establishment of hematopoietic chimeras using MHC and Thy-1 allotype as well as fluoroprotein tracing, and in vivo motility analysis using Kikume photoconversion.

Despite the advances in the treatment of heart failure over the past decades, this condition represents an enormous public health burden. Considering this unmet clinical need, the elucidation of novel mechanisms involved in heart failure pathogenesis holds the promise of developing new therapies for this prevalent and deadly disease. We focus on protection and regeneration of the diseased heart utilizing multidisciplinary approaches. We envision to translate the findings obtained in preclinical studies (in vitro and ex vivo models, in vivo preclinical small-animal models and clinically relevant large-animal models) toward clinical application or vice versa, from clinical observations back to mechanistic insights. The primary interests of our research group are in the following areas:

Preclinical studies:

• Identification of novel cardiokine systems regulating cardiac homeostasis (e.g. cardiac function, metabolism, and cell survival) under physiological conditions.
• Elucidation of cross-talk between cardiac non-myocytes (e.g. fibroblasts) and cardiomyocytes regulating cardiac growth and cell survival during cardiac remodeling.
• Development of novel small-animal models of heart failure.
• Establishment of novel large-animal models of heart failure.
• Establishment of cardiac PET-MRI in large-animal models of heart failure to measure simultaneously left ventricular function, structure, and metabolism (in cooperation with the University of Kaposvár).
• Proof of concept studies on the beneficial therapeutic effects of intramyocardial delivery of cardiokines in combination with miRNAs and lncRNAs (e.g. impact on cardiac hypertrophy, cell survival, cardiac regeneration, metabolism, angiogenesis, interstitial fibrosis, underlying signaling mechanisms [e.g. epigenetic changes, chromatin remodeling, etc]) in small- and large-animal models of heart failure.

Clinical studies:

• Identification of novel tissue-specific biomarkers (cardiokines, microRNAs, lncRNAs) for improved prediction of outcome in acute myocardial infarction.
• Identification of new tissue-specific biomarkers (cardiokines, microRNAs, lncRNAs) to improve risk stratification for cardiac resynchronization therapy in heart failure.

The goal of this long-term program is to promote the development of non-invasive diagnostic devices for the clinical care. Clinical diagnostics has entered a new era of miniaturization. Functional micro-laboratories have been developed on a microchip platform performing a broad range of analytical assays. Special interest is focused on devices for point-of-care analysis and life science (cell analysis), with future prospects towards personalized medicine.

One of our main scientific orientations is the non-invasive search for the molecular viability markers of in vitro fertilized embryos using the culture medium. In addition to the currently used morphological embryo viability assessment new parameters are required since embryos selected for transfer using visual diagnosis does not lead to successful delivery in the expected rate. The theoretical background of the patented technology is the measurement of a quantitative protein marker allowing the selection of the morphologically fit, however, functionally non-viable embryos. Our further goal is to develop a diagnostic POCT tool for clinical purposes. Also, the group focuses on structural and functional analysis of the nucleic acid content isolated from spent human embryonic culture media. Circulating cell-free DNA with both nuclear or mitochondrial origin and exosomal gene expression regulatory miRNAs get into the embryonic culture media either by active secretion or apoptotic destruction. Recognition of these molecular fractions in the culture media has generated an interest for their potential use as markers for genetic disorders. On-going projects involve the following research goals: 

•          to identify human aneuploidy-specific biomarkers by NGS sequencing techniques

•          viability prediction of the early embryo by qualitative and quantitative analysis of the genes involved in embryo development and metabolism (Zfp57, Dppa5a, Sirturin1, Sp1, Gata1, Gata2, Fgfr1, Glut3, Racgap1, Idb2 and  Per3 and the Clk)

•          Polymerase γ A gene, a major influencing factor of the embryonic mtDNA replication.

•          structural and quantitative analysis of exosomal mRNA and miRNA fractions       

In the case of serious systematic inflammation processes (sepsis) the use of personalized medicine is of vital importance to reliably evaluate the severity of the disease using biomarkers. Actin and gelsolin present in serum, the elevated level of orosomucoid in urine, or the quantification of serum total and free cortisol are all correlating with the severity of the patient’s condition. We also proved that the prognosis of the sepsis can be estimated by monitoring cortisol level during hospitalization.

In tumor diseases the in vitro invasivity of circulating tumor cells correlates with the severity of the disease and the metastatic potential of the tumor. The use of PoCT devices to detect and quantify circulating tumor cells helps to construct a personalized therapeutic strategy. Also the technology of 3D cell culturing is a potential model of cell-cell interactions, allowing the culturing of tumorous and healthy cells in the same matrix modeling in vivo circumstances. The technology is capable of examining the behavior and chemotherapic sensitivity of tumorous cells under circumstances similar to the human body.

The main goal of the Bioinformatics Research Group is not only to concentrate and conduct research on a specific scientific problem but rather to develop and implement comprehensive bioinformatics pipelines, tools and strategy for the Szentágothai Research Centre and the University of Pécs.

The proposed strategy is based on four pillars:

• bioinformatics research driving the development of new analysis methodologies,
• bioinformatics core facility providing data analysis services for biomedical researchers,
• bioinformatics education and training provided to students and researchers, and
• bioinformatics infrastructure enabling the collection, storage and analysis of data. 

The group has established a number of research collaborations with local and international research groups, developed and implemented various data analysis algorithms and methods. Some of those have already been published or are currently under submission or review. 

The research group has also set up the Genomics and Bioinformatics Core Facility and started providing sequencing and data analysis collaboration-based services for its academic and industrial partners.

We are currently developing the curriculum of a Bioinformatics MSc program at the University. We have also successfully applied for an EU grant application under the ERASMUS+ program to develop bioinformatics and biostatistics competencies for biomedical students.