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Immunology and Infection

Term: 01.02.2020 bis 31.07.2022

We have discovered Gasdermin C as a protein strongly induced in the gut epithelium by IL-4 and IL-13. We can show that Gasdermin C is released by goblet cells into the mucous layer where it binds to bacteria. Further analyses implicate that Gasdermin C has a pore forming function and promotes anti-microbial defence. We plan to elucidate the regulation of Gasdermin C, its molecular mode of action and its functional impact in vivo.

Principal Investigator
Prof. Dr. Christoph Becker
Phone: +49 9131 85-35886
E-Mail: christoph.becker@uk-erlangen.de

While the influence of T cells on bone homeostasis has been well characterized, less is known about the role of B cells. Despite that B cells are able to produce RANKL, the major cytokine regulating osteoclast differentiation, its regulation of expression remains unclear. B cells reside in the low oxygen concentrations bone niche, and adapt to the environment through the expression of HIFs. I therefore hypothesize that HIF expression in B cells could influence the development of osteoporosis.

Principal Investigator
Prof. Dr. Aline Bozec
Phone: +49 9131 85-29032
E-Mail: aline.bozec@uk-erlangen.de

To understand the role played by ubiquitination of type I interferon in the pathogenesis of inflammatory bowel disease we intend to induce DSS colitis in two newly generated conditional mouse strains i.e. Stat2 and Smurf2 in experimental colitis models. CRISPR/Cas, three dimensional organoids coupled with Nanostring and RNA-Seq/GO analysis will be used to understand molecular mechanisms underlying DSS findings. Data will be validated using samples from IBD patients and controls.

Principal Investigator
Dr. Dr. Mircea Chiriac
Phone: +49 9131 85-35899
E-Mail: mircea.chiriac@uk-erlangen.de
Principal Investigator
Prof. Dr. Markus Neurath
Phone: +49 9131 85-35204
E-Mail: markus.neurath@uk-erlangen.de

Fibrotic diseases account for 45% of the deaths in the developed world. We demonstrate that the nuclear receptor TR4 is overexpressed in fibrotic tissues in a TGFbeta-dependent manner. TR4 promotes fibroblast-to-myofibroblast transition and collagen release. Knockout of TR4 prevents fibroblast activation and ameliorates experimental fibrosis. In the proposed project, we aim to characterize the molecular mechanisms of fibroblast activation by TR4 and the antifibrotic effects of TR4 inhibition.

Principal Investigator
Prof. Dr. Jörg Distler
Phone: +49 9131 85-34742
E-Mail: joerg.distler@uk-erlangen.de

 

Term: 01.01.2020 – 30.06.2022

Inflammasomes play a pivotal role in the immune response against pathogens, but also in the pathogenesis of inflammatory disorders. Our data indicate that inflammasome activation in DCs is leading to full DC stimulation without induction of pyroptosis. We hypothesize that uncontrolled inflammasome stimulation in DCs might be key component in inflammatory disorders. In this study, we want to elucidate the mechanisms in this specific inflammasome activation in primary DC.

Principal Investigator
Prof. Dr. Diana Dudziak
Phone: +49 9131 85-39346
Email: diana.dudziak@uk-erlangen.de

Term: 01.01.2020 – 30.06.2022

 

Recently, we detected Borna disease virus (BoDV-1) as the cause of human fatal encephalitis. Previous studies have addressed the immune response and viral replication, but the host cell receptor of BoDV-1 remained unknown. We will use an unique BoDV-1 patient isolate to search for this receptor, and we will address the possible direct, non-immune related neuropathogenic potential of BoDV-1, as well as antiviral (chemo)therapeutic options, in IPSC derived human neuronal 3D organoid cultures.

Principal Investigator
Prof. Dr. Armin Ensser
Phone: +49 131 85-22104
Email: armin.ensser@fau.de

Term: 01.02.2020 – 31.07.2022

 

We identified RANTES as a key regulator of the resolution of allergic asthma in human and murine studies. Resolved symptomatic episodes of asthma in children, were found to be associated with elevated serum levels of RANTES indicating the involvement of RANTES in the resolution of allergic asthma. In a murine model after allergen (HDM) challenge, RANTES cured allergic asthma trait. In this project, we want to better understand the mechanism of RANTES mediated resolution of allergic asthma.

Principal Investigator
Prof. Dr. Susetta Finotto
Phone: +49 9131 85-35883
Email: susetta.finotto@uk-erlangen.de

Term: 01.01.2020 – 30.06.2022

 

HIV patients coinfected with CMV show increased morbidity and mortality, even on therapy. Despite high coinfection rates, surprisingly little is known about molecular interactions of CMV and HIV. We found that CMV blocks the HIV restriction factor SAMHD1 to facilitate its own replication. This finding finally provides a handle to explain how CMV enhances HIV replication in the host. Thus, we will address the working hypothesis that CMV infection boosts HIV replication by inactivating the SAMHD1.

Principal Investigator
Prof. Dr. Thomas Gramberg
Phone: +49 9131 85-36481
Email: thomas.gramberg@fau.de

Term: 01.05.2020 – 30.11.2022

T cell mediated intestinal inflammation in acute Graft-versus-Host-Disease (GI-GvHD) represents a life-threatening and therapeutically challenging complication in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Interestingly, the role of tissue-resident memory T cells (Trm) in this context is unknown. Here, we plan studies to assess the development, migration, location and functionality of Trm cells in GI-GvHD both in murine experimental models and in men.

Foto Zundler
Principal Investigator
Prof. Dr. Kai Hildner
Phone: +49 9131 85-35908
E-Mail: kai.hildner@uk-erlangen.de
Principal Investigator
Dr. Sebastian Zundler
Phone: +49 9131 85-35000
E-Mail: sebastian.zundler@uk-erlangen.de
Principal Investigator
Prof. Dr. Maike Büttner-Herold
Phone: +49 9131 85-26088
E-Mail: maike.buettner@uk-erlangen.de

 

SAPHO syndrome is a rare inflammatory disease of the skeleton and skin with unsolved etiology, but suspected causal/ disease-contributing genetic factor(s). We identified several rare PLXNA1 variants in patients with SAPHO syndrome. We propose to identify the molecular mechanisms by those human variants that lead to disease. Our study will allow to understand the etiology of SAPHO and to pave the way for planned analyses in vertebrates and genetic follow-up studies.

Principal Investigator
Prof. Dr. Ulrike Hüffmeier
Phone: +49 9131 85-26477
E-Mail: ulrike.hueffmeier@uk-erlangen.de

Our preliminary data identified a unique Cx3Cr1-positive macrophage subset that forms a protective barrier around the joint and counteracts inflammation. Accordingly, we will address the developmental origin and differentiation pathways of these specific macrophages and try to understand the molecular basis of their anti-inflammatory properties. Moreover, we will address the relevance of these findings for human diseases such as rheumatoid arthritis.

Principal Investigator
Prof. Dr. Gerhard Krönke
Phone: +49 9131 85-34742
E-Mail: gerhard.kroenke@uk-erlangen.de

Dendritic Cells (DCs) are indispensable for the protection from pathogens. Additionally, natural antibodies (nAbs) reacting to evolutionary conserved epitopes foster fast targeted response. Leishmaniasis is an important tropical disease with different manifestations. However, the first events in infection and determination of T/NK cell responses by DCs and nAbs are not fully understood. We now aim to unravel early determining factors for clinical outcome in leishmaniasis on a single cell level.

Principal Investigator
Dr. Christian Lehmann
Phone: +49 9131 85-29321
E-Mail: christian.lehmann@uk-erlangen.de
Principal Investigator
PD Dr. Ulrike Schleicher
Phone: +49 9131 85-23647
E-Mail: ulrike.schleicher@uk-erlangen.de

Term: 01.02.2020 – 30.09.2022

HCMV replication is characterized by viral CDK-cyclin interaction. The CDK-like viral kinase pUL97 interacts with human cyclins. CycB1 is phosphorylated upon the interaction, dependent on pUL97 activity, whereas cycT1/H interaction stimulates pUL97 activity and substrate phosphorylation. Regions for cyclin interaction and antiviral drug resistance show overlaps in pUL97, so that this correlation will be elucidated in terms of viral fitness for the development of a novel antiviral strategy.

Principal Investigator
Prof. Dr. Manfred Marschall
Phone: +49 9131 85-26089
E-Mail: manfred.marschall@fau.de
Principal Investigator
Prof. Dr. Heinrich Sticht
Phone: +49 9131 85-24614
E-Mail: heinrich.sticht@fau.de

Inflammation within the CNS can directly affect neuronal structures. Thus, molecules controlling inflammatory responses are of upmost importance. The immune-regulatory CD83 molecule is highly expressed by microglia and tissue-resident macrophages and thus, represents a crucial factor for microglial activation and the neuro-immune crosstalk. Since, its regulation and function in these cells has not been elucidated we will investigate this during immune homeostasis and neuroinflammation.

Principal Investigator
Prof. Dr. Alexander Steinkasserer
Phone: +49 9131 85-36725
E-Mail: alexander.steinkasserer@uk-erlangen.de

Term: 01.01.2020 – 30.06.2022

 

In this project, we will analyse the regulatory mechanism for the maintenance of lung-resident memory T-cells. The impact of secondary events of inflammation or infections on the pre-existing immunity will be the major focus. Furthermore, we determine whether the differential induction of the immunity by either a primary infection or a gene-based vaccine might play a role in this context.

Principal Investigator
Prof. Dr. Matthias Tenbusch
Phone: +49 9131 85-26784
Email: matthias.tenbusch@uk-erlangen.de

Term: 16.03.2020 – 15.09.2022

The highly oncogenic retrovirus Human T-cell leukemia virus type 1 (HTLV-1) causes incurable neoplastic or inflammatory diseases. The viral accessory protein p8, which is proteolytically cleaved from the pre-cursor p12 and transported to target cells prior to infection, is important for establishing persistent infections in vivo. Here, we aim to identify the protease cleaving p12 into p8, to inhibit this protease, and to assess the impact of blocking of p12/p8 processing on viral persistence.

Principal Investigator
Dr. Andrea Thoma-Kreß
Phone: +49 9131 85-26429
E-Mail: andrea.thoma-kress@uk-erlangen.de

As lymphatics in the inflamed joint in rheumatoid Arthritis drain specifically the popliteal lymph node (pLN) where the adaptive immune response is initiated, we investigated a population of stromal cells in the pLN, namely the fibroblastic reticular cells (FRC). Our preliminary data show a significant immunomodulatory potential of pLN FRCs in inflammatory arthritis mouse models. Therefore, we hypothesize that specifically pLN stromal FRCs play a so far neglected role in the early onset of RA.

Principal Investigator
Prof. Dr. Mario Zaiss
Telefon: 09131 85-33794
E-Mail: mario.zaiss@fau.de