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Department of Paediatrics

Projects

  • Iron metabolism of the human placenta

    Iron metabolism of the human placenta – the key to understand iron transfer from the mother to the fetus

    • Project Number: LSC17_008
    • Project Lead: Hans Salzer, Karl Landsteiner University of Health Sciences / Division of Paediatrics (University Hospital Tulln)
    • Project Partner: Medical University of Vienna / Institute of Medical Genetics, Landesklinikum Mistelbach / Department of Pediatrics and Adolescent Medicine
    • Duration: 36 months starting from 05.11.2018

    Background

    Background:
    Iron is an essential trace element that is required by all cells, but toxic when present in excess. Iron deficiency is the most common form of micronutritional deficiency worldwide. Preterm infants as well as pregnant women are most likely to suffer from it. During pregnancy, the placenta is the major interface of nutritional exchange between mother and developing fetus. Although mammalian iron metabolism is in general very well characterized, surprisingly little is known about iron metabolism and transfer in the human placenta.
    Aims:
    Inspired by the substantial gaps of knowledge on human placental iron metabolism and by our preliminary data on human placenta, we aim to study:
    (1) The iron metabolism and transport in human placentas and appropriate cell models.
    (2) The iron status of healthy mother-child-pairs in relation to placental expression of proteins involved in iron metabolism as well as in relation to placental iron.
    Methods:
    In the proposed study, which is based on overall 105 healthy, non-anemic mother-child-pairs, iron status of pregnant women and neonates in relation to placental expression and localization of iron metabolising and transporting proteins is investigated. In vitro experiments with human placental cells (primary trophoblast cells, Hofbauer cells, primary placental endothelial cells, and the two placental cell lines BeWo and HUVEC) will be conducted to examine and confirm the involvement of TFR1, FPN1, ZIP8 and other (to be selected) candidate proteins in placental iron metabolism and transport.
    Innovation:
    The proposed study is the first, which combines iron status of mother-child-pairs with extensive basic research (protein expression, function, and localization) on human placentas. The key proteins involved in human placental iron metabolism and transport will be examined for the first time together. The study is based on a comparably large number of mother-child-pairs. With the proposed study we aim to add new knowledge on human placental iron metabolism and transfer. We expect long-term benefits arising from this innovative approach, which will enable us in the long run to optimize the therapy of maternal and preterm iron deficiency.

  • Personalized Diagnostics

    Advanced personalized diagnostics to overcome severe side effects of protein therapeutics

    • Project Number: LSC16_008
    • Project Lead: Peter Allacher, IMC University of Applied Sciences Krems / Applied Bioanalytics & Drug Development
    • Project Partner: Karl Landsteiner University of Health Sciences / Division of Paediatrics (University Hospital St. Pölten)
    • Duration: 36 months starting from 01.09.2017

    Background

    Therapeutic protein drugs have been widely used to treat a variety of diseases including cancer, autoimmune diseases, neurological diseases, metabolic diseases, bleeding disorders and others. The global protein drug market reached nearly $174.7 billion in 2015 and should reach nearly $248.7 billion by 2020. Although most protein drugs offer a favourable benefit-risk ratio, one key hurdle for the maintenance of clinical efficacy and safety has been the development of unwanted immune responses against protein drugs, in particular the development of anti-drug antibodies. Some patients develop pathogenic antibodies which neutralize the biologic activity of the protein drug or cause devastating health problems such as anaphylaxis or autoimmune pathologies. Currently, there is no diagnostic tool which can predict and distinguish the development of harmless or pathogenic antibodies in an individual patient. Therefore, basic research efforts are required to better understand immune regulation and nature of harmless and pathogenic anti-drug antibodies and to create the scientific basis for the development of novel diagnostics. Early diagnosis of evolving pathogenic antibodies would provide a window of opportunity for early immune intervention which could prevent pathogenic immune responses. One prominent example of pathogenic anti-drug antibodies is the development of neutralizing antibodies against factor VIII (FVIII) following replacement therapy of hemophilia A patients with human FVIII products. The antibodies neutralize the biological activity of FVIII and render replacement therapies ineffective which can result in life-threatening bleeding complications. In this project application, we propose to close a major gap in current understanding of the nature and evolution of pathogenic antibodies against FVIII and their differentiation from non-pathogenic antibodies in patients with severe hemophilia A. We aim to generate novel data on the temporal association between epitope specificity (protein epitopes versus carbohydrate epitopes), affinity, isotype/IgG subclass profiles and functional activities of antibodies against FVIII which develop in patients following replacement therapy with FVIII products. The possibility to combine basic research with the analysis of longitudinal samples obtained from patients undergoing FVIII therapy will provide a unique opportunity to directly translate novel research findings into clinical application. The data coming out of this project will provide the scientific basis for the development of novel diagnostic tools, such as FVIII-specific microarrays, which will allow physicians to differentiate patient-specific characteristics and design personalized treatment approaches, and ultimately improve patient outcomes.

  • Toxicokinetics of mercury in the placenta

    The toxicokinetics of mercury in the human placenta: correlation between genotype and phenotype in healthy and diseased placentas

    • Project Number: LSC15_014
    • Project Lead: Hans Salzer, Karl Landsteiner University of Health Sciences / Division of Paediatrics (University Hospital Tulln)
    • Project Partner: Medical University of Vienna / Institute of Medical Genetics, Karl Landsteiner University of Health Sciences / Division of Paediatrics (University Hospital St. Pölten)
    • Duration: 49 months starting from 01.12.2016

    Background

    Normal function of the placenta is pivotal for optimal fetal growth and development. The etiology of placental dysfunction is multifactorial with abundant gene and environment interactions. Placental dysfunctions are implicated in pregnancy complications such as gestational diabetes (GDM), pre-eclampsia (PE) and intrauterine growth restriction (IUGR). We intend to examine a certain aspect of reproductive toxicology, the mercury toxicokinetics in the healthy and diseased (GDM, PE, IUGR) human placenta. Based on the available data on the involved genes/proteins in mercury toxicokinetics from the healthy placenta, we now aim to compare their role and function in healthy and diseased placentas. We are interested whether mercury toxicokinetics are altered in dysfunctional placentas, which is a relevant issue in reproduction toxicology and individualized pregnancy care. We observed variable expression levels of placental proteins involved in mercury toxicokinetics. Our hypotheses are that 1) sequence variations in the candidate genes contribute to altered placental protein expression and as a consequence to altered toxicokinetics in the placenta, and 2) that the genetic background for mercury toxicokinetics is different between healthy and diseased placentae (GDM, PE, IUGR). The placenta is a unique organ for investigating genotype-phenotype relationship because the organ is accessible, protein levels and functions can relatively easy be determined, and also primary cells can be obtained. Methyl mercury (MeHg) is regarded as a model substrate because various amino acids, hormones, cancer drugs, and xenobiotics use at least in part the same transporter and metabolizing/detoxifying systems as the metal species. Studying transport and metabolisation/detoxification of MeHg in healthy and diseased placentas provides valuable data not only for the field of reproductive toxicology. Three groups of proteins related to mercury toxikokinetics are involved in placental (dys)function. There is evidence that amino acid transporter levels are altered in both IUGR and fetal overgrowth and that PE goes along with an altered oxidative defense in the placenta. There is some evidence that also ABC transporters are involved in PE and IUGR. We suggest six proteins, i.e., amino acid transporters LAT1 and b0,+, GSH system related enzymes GGT1 and GSTA1 and ABC transporters MRP1 and MRP3 to be examined in the healthy and diseased placenta. In the proposed study we aim to confirm (1) whether the protein specific effects on mercury toxicokinetics observed in previous experiments are direct effects. Based on the knowledge which proteins are directly related to mercury toxicokinetics, we will determine (2) which known functional genetic variants are related to placental protein expression and mercury contents by comparing healthy and diseased (GDM, PE, IUGR) placentas.

Events

  1. 14 Mar

    Open House at KL University - March 2020

    14. March 2020, 10:00 - 14:00
    Karl Landsteiner University, Dr.-Karl-Dorrek-Straße 30,3500 Krems, Trakt Y, Erdgeschoß
  2. 27 Mar

    International Skills Lab Symposium 2020

    27. March 2020, 09:00 - 28. March 2020, 18:00
    Karl Landsteiner Privatuniversität für Gesundheitswissenschaften, Skills Lab, Trakt Y
  3. 16 Nov

    Open House at KL University - November 2019

    16. November 2019, 10:00 - 14:00
    Karl Landsteiner Privatuniversität, Dr.-Karl-Dorrek-Straße 30,3500 Krems, Trakt Y, Erdgeschoß