Research topics
Cytoprotection in experimental peritoneal dialysis
Christoph Aufricht
Peritoneal dialysis represents an unique
opportunity to transfer HSP-mediated cytoprotection from bench to bedside, and
to apply this approach as an innovative therapeutic tool, because the clinical
setting of PD consists of repeated timed (and thoroughly predictable) exposure
of mesothelial cell to acute and uniform cellular insults upon PDF exposure.
Up to date methodology will use in-vitro and in-vivo models of peritoneal
dialysis, cell-outcome analysis based on FACS analysis, and protein expression
analysis by western and proteomic analysis. Read
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PubMed Publications*
Cytoprotection in intestinal disorders
Bettina Bidmon-Fliegenschnee
The main focus of our pediatric
gastroenterology group is cytoprotection in intestinal disorders. The
intestine displays the largest interface between human and its environment,
and for maintaining health or preventing tissue injury and other different
intestinal diseases an intact intestinal barrier is essential. Our main
emphasis is therefore the intestinal barrier. Our studies will hopefully help
to include aspects of HSP-mediated cytoprotection into developing new
therapeutic modalities.
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PubMed Publications*
Alloantibody/complement in organ transplant rejection
Georg A. Böhmig, MD
There is increasing evidence for a critical contribution of alloantibody/complement to organ transplant rejection. Presently, the diagnosis of antibody-mediated rejection (AMR) is based on biopsy (capillary deposition of complement split product C4d). We have recently demonstrated the possibility of flow cytometric detection of HLA alloantibody-triggered C4d deposition in vitro. The major goal of this analysis is to evaluate associations of serologically detected C4d deposition in vitro with the occurrence of deleterious C4d-positive AMR in vivo. After establishment of techniques for solid phase- and cell-based complement split product detection we will analyse associations of in vitro complement deposition with specific morphological and clinical features of AMR in a large prospective cohort of kidney transplant recipients. The set-up of accurate non-invasive diagnostics for deleterious humoral injury can be expected to contribute to remarkable improvements in the management of transplant recipients. Read more ...
Effect of MDR1 polymorphisms on tacrolimus and cyclosporine A trough
levels after kidney transplantation
Manuela Födinger
Evidence is accumulating that drug levels are genetically
influenced. It has been shown that renal transplants showing one or two
CYP3A5*1 alleles achieve twofold lower dose-normalized tacrolimus blood
concentrations as compared to CYP3A5*3/*3 individuals. P-glycoprotein is a
transmembrane efflux pump that removes toxic substances from cells. It is
currently unknown, whether polymorphisms in the corresponding gene, ABCB1
(alternative title: MDR1, multi-drug resistance 1), influence target blood
levels of immunosuppressive drugs in renal transplant patients. To fill this void
we intend to investigate kidney transplant recipients for an association of
two polymorphisms located within in the 5’ upstream regulatory region of MDR1
(-692T>C, -2352G>A) with dose-normalized immunosuppressant concentrations.
Because no information is available about the prevalence of both polymorphisms
among Caucasians, allele frequencies will be assessed among > 1500 individuals,
including healthy individuals, kidney transplant recipients, patients on
chronic hemodialysis and peritoneal dialysis treatment. The data obtained in
this project could allow for early recognition of individuals requiring higher
or lower doses of immunosuppressants to achieve target drug levels.
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PubMed Publications*
Immune Tolerance in Hematopoietic Stem Cell Transplantation (HSCT)
Andreas Heitger
Hematopoietic stem cell transplantation (HSCT) is still
associated with a high risk of transplantation related morbidity and mortality.
Adoptive T cell therapies after HSCT aim to support the recipient’s
compromised immunity with protection against environmental pathogens but
without aggravating the risk of graft-versus-host disease. The expression and
activity of the tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase (IDO)
in human dendritic cells is a promising tool to induce all-antigen specific
tolerance in allogeneic T cells. This approach is currently probed by
extensive in vitro and in vivo studies.
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PubMed Publications*
Identification of panel reactive antibody specificities in renal
transplant recipients
Rudolf Oehler
The proposed project is based on systematic proteomics
analysis to characterise antigens of donor-specific antibodies. It aims to
identify proteins of donor lymphocytes which are targeted by antibodies from
sera of renal transplant recipients. The results will contribute to a better
understanding of the role of humoral immunology in renal transplantation and
may become a starting point of many future studies.
In the present project the clinical and scientific expertise of
transplantation surgeons is combined with the experimental know how of
biochemists and analytical chemists. Blood is taken from renal graft
recipients before and after transplantation. These samples are used to
identify targets of donor-specific antibodies by the novel proteomics approach
IP2D which combines immune precipitation (IP) with two-dimensional gel
electrophoresis (2D) and mass spectrometry.
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PubMed Publications*
Pharmacologic Inhibition of Angiogenesis in Portal Hypertension
Markus Peck-Radosavljevic
Portal hypertension is mostly the consequence of
cirrhosis of the liver and its complications the most common cause for death
in liver disease. Medical therapy is well established but of limited efficacy.
We intend to develop new drug therapies for portal hypertension based on
better understanding of the pathophysiology. By investigating angiogenesis in
an animal model with up to date hemodynamic and molecular biologic techniqhes
and applying the knowledge gained in our clinical Hepatic haemodynamic
Laboratry, we hope to find new and better drug therapies for this complication
of cirrhosis.
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PubMed
Publication*
Intrauterin stem-cell based interventions to induce postnatal
immuntolerance
Arnold Pollak, MD
The main focus of our research group is to establish
intrauterine approaches in well accepted rodent models to induce postnatal
directed immunotolerance using the approach of costimulatory blocking.
Experimental data so far suggest that the intrauterine period offers a special
opportunity to pretreat or prepare the fetus with regards to immunotolerance
against a later renal allograft.
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PubMed Publications*
Mechanisms of allograft injury induced by alloantibody-mediated complement
activation in renal transplantation
Heinz Regele
With our approach of creating an “autologous” in-vitro
test system, our research group hopes to provide biologically and clinically
meaningful insights into the molecular mechanisms of antibody-mediated
rejection (AMR) in renal transplantation. That might eventually pave the way
for the development of novel strategies in diagnosis and treatment of AMR.
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PubMed Publications*
Molecular dissection and immunomodulatory strategies
Marcus Säemann
The principal research aims are to further dissect
currently employed immunosuppressive targets that play a fundamental role
within the innate immune system. Hence both cell culture as well as
biochemical analysis of essential signal transduction events of the various
cell populations within a functional context may further open avenues of
immunomodulatory strategies employed in patients with allogeneic transplants,
autoimmune disease and cancer.
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PubMed Publications*
Does immunosuppression in organ recipients affect the T-cell cytokine profile and T-reg function?
Zsolt Szépfalusi
The aim of the study focuses on the assessment of differences of
proliferative responses, cytokine profiles and regulatory markers among
children and adolescents under immunosuppression for organ recipients having
developed Type-I allergy or allergic sensitization.
Techniques that are being applied are: intracellular
cytokine staining, flow cytometry, polyclonal, antigen-specific and
allergen-specific proliferation assays, RT-PCR. The work will be done at the
local research unit of the Department of Pediatrics in cooperation with the Institute
of Pathophysiology at the MUW.
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PubMed Publications*
Immunological tolerance in transplantation and allergy
Thomas Wekerle
Our group focuses on translational research in the area
of two common immunological conditions: organ transplantation and allergy. We
are interested in the development of experimental tolerance regimens with
relevance for these two indications and the in-depth mechanistic analysis of
such models.
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PubMed Publications*
* Attention: Search process is not supervised and publications of other authors with similar names may be included.
