Institute for Translational Medicine
Research groups of the Institute:
- Energy Balance Research Group (Leader: Dr. Márta Balaskó): Introduction of the Research Group: The incidence of aging increases dramatically in populations all over the world, along with the occurrence of age-related metabolic disorders such as middle-aged obesity and aging anorexia leading to muscle atrophy (sarcopenia) in old populations. Population aging is particularly rapid among women resulting in ‘‘feminization of old age’’, therefore investigation of sex-differences is of primary importance. Long-term body weight regulation and age-related changes in body composition show similar trends in laboratory rodents and humans, therefore regulatory changes may also been assumed in the background. Age-related shifts in the responsiveness to certain catabolic mediators (e.g. to centrally applied leptin, centrally applied melanocortins, peripherally applied cholecystokinin) that may contribute to the development of middle-aged obesity and aging anorexia (i.e. strong effects in young adult, diminished responsiveness in middle-aged and pronounced effects in old age-groups) suggest that age-associated alterations in other neuropeptide systems or in other peripheral mediators and hormones may also be involved in the development of age-related obesity or aging anorexia. Long-term nutritional states, such as obesity or life-long caloric restriction and special diets (e.g. ketogenic or Mediterranean diets) may also influence the regulation of energy metabolism strongly. Apart from them, physical activity and training interventions are also known to decrease body weight and slow down aging. The main objective of our research group is the elucidation of the contribution of age-related regulatory changes to obesity developing at an ever earlier age and to weight loss and muscle atrophy in the elderly. We are also studying the special mechanisms affecting energy balance activated by long-term caloric restriction, specific diets or different forms of physical activity. We aim to investigate their potential contribution to the prevention of middle-aged obesity and sarcopenia of the elderly.
- Translational Research Group for Age Life-Quality Inflammation and Sexhormones (Leader: Dr. János Garai)
- Gerontology Research Group (Leader: Dr. Erika Pétervári): Research topic: From the point of view of energy homeostasis, aging is characterized first by an increase in body weight and fat mass (middle-aged obesity), then, in old age-groups by a drop in body weight and sarcopenia. Both obesity epidemic and aging anorexia causing weight loss of old people in the Western world present severe public health burden on our society. Neuropeptides may play a role in the central regulatory mechanisms of these processes. Our animal research focuses on these mechanisms. To distinguish between the effects of aging and those of body composition, we carry out the experiments in calorie-restricted and also in diet-induced obese animals. The perinatal period is known to be critically important in the development of appetite regulating centers involving neuropeptides of hypothalamus-adipose tissue axis and the gut–brain communication. Our complex analysis of the effects of different peptides on a wide range of parameters of energy balance aims to clarify: How do the energy balance and the most important regulatory neuropeptides change during the course of life in perinatally overfed/underfed offsprings? We assume, that maternal high fat diet and obesity accelerate those age-dependent biphasic changes in neuropeptidergic regulation of body weight, which may promote an earlier onset of both middle-aged obesity and aging anorexia leading to sarcopenia. The exploration of these long-term mechanisms will lead to implementation of interventional strategies and improved translation of proposed interventional therapies (nutritional corrections during pregnancy or in the early neonatal period to reverse an inadequate programming) before they can be implemented in humans. That will have beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders. In order to identify new therapeutic targets of obesity, we test novel peptide mediators with potential roles in the regulation of energy balance and the effects of inranasal application of the peptides (a clinically viable mode of delivery).
- Multidisciplinary Translational Research Group (MRG) (Leader: Prof. Péter Hegyi): MRG was established to facilitate clinical studies. It draws on the expertise of specialists for valuable support for these studies. One such set of specialists is the IT Group, which maintains the computer equipment and is engaged in regular software development. The Biostatistics Group is the other one. Physician researchers often face the problem of how to summarize measurement data and what conclusions to draw from that data on a particular phenomenon. They need biostatistics to be able to do this properly. Our third group deals with Operative Data and Clinical Studies. They do the work of providing quality assurance, liaising with foreign and domestic partners, securing various ethical permissions, maintaining registers and data management. This is also tied to the Physician Groups, which ensure dialogue between researchers and the MRG staff, with an eye to both basic and clinical studies. A key MRG task is to provide transparency, which is indispensable for gaining support from society. The MRG therefore consists of a Media Group as well. Website: https://tm-centre.org/
- Translational Molecular Genetics Research Group (Leader: Dr. Eszter Hegyi): Chronic pancreatitis is a progressive inflammatory disease of the pancreas leading to irreversible morphological changes and impairment of both exocrine and endocrine functions. Genetics plays an important role in the pathogenesis of chronic pancreatitis, especially in children. Over the past 20 years the role of genetic factors in the etiology of chronic pancreatitis has been extensively studied and a mechanistic model in which premature trypsinogen activation plays a central pathogenic role has been established. More recently, an alternative pathomechanism unrelated to accelerated intrapancreatic trypsinogen activation has been revealed, in which mutation-induced misfolding and consequent ER stress lead to acinar cell damage and pancreatitis. The laboratory within the Institute for Translational Medicine of the University of Pécs, Hungary has been established recently with an intent to build an internationally competitive, state-of-the-art, vibrant scientific laboratory dedicated to the mentored training of young scientists in the field of pancreatology and committed to finding cures for the disorders of the pancreas through basic and translational research. The Center’s research program focuses on pathological mechanisms of pancreatitis using human genetic studies, protein biochemistry, cell culture models and animal models. Human genetic studies take advantage of the Eastern and Central European Pancreatic Study Groups Biobank and Registry for Pancreatic Patients (ECEPSG RPP) initiated by the Hungarian Pancreatic Study Group and directed by Prof. Péter Hegyi who is also the chair of the Institute for Translational Medicine. The Center is also willing to invest in animal research related activities with the goal of developing genetic models of pancreatitis. Using animal models of genetically determined chronic pancreatitis we aim to study both pathomechanisms, the trypsin-dependent and the ER stress related pathways in vivo. Applied laboratory techniques: In the center the students have the opportunity to master different techniques used in molecular genetics (DNA/RNA isolation, PCR, RT-PCR, Sanger sequencing, mutagenesis, Western blot), biochemistry (affinity chromatography, enzyme activity measurements), cell culture and mouse model experiments. The students also will have the opportunity to perform some of the experiments in the laboratory of Professor Miklos Sahin-Toth (Boston University), who is a world-renowned researcher in the field of chronic pancreatitis focusing on the genetic background of the disease. Professor Sahin-Toth has a dual role in the projects; he is the director of the Center for Pancreas Disorders at the University of Pécs and he also serves as an international collaborator.
- Translational Research Group for Vascular Dyfunction (Leader: Dr. Margit Solymár): The obesity epidemic is one of the most serious public health challenges in the European region: more than one in two adults is overweight or obese. Obesity is associated with inflammatory response and increased oxidative stress leading to vascular and metabolic dysfunction and increased morbidity and mortality. Obesity is the basis for the development of major non-infectious diseases (such as metabolic syndrome, hypertension, insulin resistance, type 2 diabetes mellitus, dyslipidemia, subsequent pathological vascular changes and atherosclerosis). Therefore, obesity reduces life expectancy and reduces quality of life. In the background of cardiovascular complications, endothelial dysfunction develops before the development of atherosclerosis. The chronic inflammatory state of obesity causes poor control of the endocrine and paracrine effects of adipocyte-derived factors, which disrupts vascular homeostasis and contributes to the disruption of endothelial vasodilatory effects and subsequent hypertension. In our experiments, we aim to observe, reverse and prevent abnormal vascular functions after obesity caused by high-fat diet and in type 1 and type 2 diabetes mellitus with a novel therapeutic approach by activating the PAC1, VPAC1 and VPAC2 receptors. We expect that increased vascular resistance and vascular impairment such as endothelium-dependent and -independent responses could be restored. The objective of the research is to identify effective interventions and possible targets for drug development. This would help to avoid the widespread negative effects of different components of the very common obesity and metabolic syndrome, which impairs the quality of life and limits longevity.
- Thermophysiology Research Group (Leader: Dr. András Garami). Introduction: Normal body temperature – which is essential for life – is maintained by various thermoregulatory mechanisms. Any disturbance in the thermoregulatory processes jeopardizes the health of the whole organism. Thermoregulatory disorders can be found in a plethora of pathological conditions, including febrile diseases, systemic inflammation (e.g., sepsis), organ dysfunctions (e.g., pancreatitis), heat stroke, and hypothermia. Because of the wide range of thermoregulatory disorders, it is of utmost importance to discover the related pathophysiological processes. More and more influencing factors are identified in the thermoregulation system, such as the pH status and transient receptor potential channels. In our research, we aim at identifying the neural substrates and molecular mediators involved in the thermoregulatory processes mainly in different animal models, but to some extent also in human studies. The newly obtained findings can further advance the knowledge of bodily homeostasis, moreover, they can open new directions in clinical practice, most of all intensive therapy, and other sciences. For example, successful development of drugs that are designed specifically to target body temperature, could pave the road to pharmacologically controlled temperature management, thereby advancing the therapeutic approaches in clinical conditions with thermoregulatory disorders.