Research groups
HCEMM-USZ Cerebral Blood Flow and Metabolism Research Group
Continuous, undisturbed blood supply to the brain is essential to optimal neural function. The brain accounts for 2% of the body mass, yet it receives 15% of the cardiac output and consumes 20% of the full body's oxygen supply. Any reduction or a very brief cessation of cerebral blood flow has, therefore, a detrimental impact on brain function. The goal of our research is to understand the cellular mechanisms of neuronal injury in acute cerebrovascular disorders.
Our ongoing research focuses on ischemic stroke. The development of effective strategies to limit the progression of secondary injury is of fundamental importance to improve the prospect of successful recovery. As a first step, it is essential to recognize distinct injurious phenomena that evolve over the subacute and chronic phases of ischemic brain injury (e.g. brain edema, vasospasm, oxidative stress, excitotoxicity). The phenomenon known as spreading depolarization is a central mechanism of secondary ischemic brain injury. We explore the signaling pathways set in motion by spreading depolarizations. We also study the impact of aging on the progression of ischemic brain injury. This is a timely and pertinent area of research since the incidence of ischemic stroke increases exponentially after the age of 50 years. Our work is essentially translational; the data generated is expected to be turned into the design of effective therapies to alleviate stroke symptoms.
Members:
- Prof. Dr. Eszter Farkas
- Dr. Ákos Menyhárt
- Dr. Szilvia V. Kecskés
- Dr. Rita Frank
- Dr. Réka Tóth
- Anna Törteli
- Dr. Armand Rafael Bálint
- István Pesti
- Petra Somogyi
Pluripotent Stem Cell Research Group
As Europe is an aging society, the prevalence of neurodegenerative diseases, especially AD is increasing and based on WHO predictions, AD will be the second leading cause of death after cardiovascular diseases by 2040. Furthermore, there is no effective treatment against AD. As for research aspects, the currently used animal models to test AD are far from eligible, since cognitive functions not necessarily correlates with tau phosphorylation and amyloid beta (Aβ) accumulation. On the other hand, obtaining primary cells from diseased brain is almost impossible. Based on these facts, the development of a novel model to understand AD pathogenesis in a more detailed way is urgent.
It is well known that beside neurons microglia cells play pivotal role in the pathogenesis and in the progression of AD by shifted cytokine and chemokine production. The Dinnyés Team has availability to hiPSC cells from familiar (f) and sporadic (s) AD patients with different genetic background. The team will differentiate hiPSCs towards resting microglia (M0) and shifting them towards proinflammatory (M1) and anti-inflammatory (M2) phenotype with different cytokines and chemokines. The phenotypic analysis of M0, M1 and M2 microglia from sAD, fAD and healthy control will be performed.
We hope that our in vitro cell based complex model will be suitable for discovering the background of the differences between sAD and fAD. Moreover, we will gain important pieces of information about altered microglia function in the pathogenesis of AD. Our final goal is to find novel drug targets and to perform preclinical tests of drug candidates.
Members:
Neuroinflammation Research Group
Different activated and ramified microglia populations in embryonic- or newborn derived primary cortical cultures can be separated with different morphological, molecular, immuncytochemical and functional (proliferation and phagocytosis capacity) methods. In our study, we explore the action of anti- and proinflammatory compounds on the re-arrangement of cytoskeletal actin in microglial cells.
We apply in our in vitro system morphological and functional assays (cell proliferation and viability, phagocytosis, motility test and several gene expression measurement-based methods). Beside the examination of transcriptional and epigenetic regulation of the pro-and anti-inflammatory gene expression, we also analyze specific intracellular signalization pathways potentially implicated in the activation of the microglia.
We manipulate environmental factors in the cultures (temperature, inflammatory and osmotic factors) in combination with the application of inhibitors of actin cell cortex re-arrangement, or modulators of inflammatory process.
Our in vitro experiments are used to replicate various aspects of neuroinflammation, neurodegeneration and regeneration (typical of Alzheimer’s or Huntington disease) and are expected to contribute to the better understanding of pro- and anti-inflammatory signaling in microglia. Our work contributes to a multidisciplinary research panel, in which the dysfunction of cellular signaling in the nervous tissue is studied to aid the development of effective therapeutic strategies for the treatment of neurodegenerative disorders.
Members