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Current projects

Term: 01.11.2018-31.10.2019

The aim of this project is to analyze the role of the co-stimulatory molecule Btn2a2 in the development and / or pathology of RA and to lay the foundations for future research to understand the underlying mechanisms of action of Btn2a2 during the dissolution of inflammation decrypt.

Term: 15.11.2018-14.11.2019

The aim of this work is gaining knowledge about the ability of quantitative susceptibility mapping (QSM) to monitor de- and remyelination processes. QSM is a rather novel magnetic resonance imaging (MRI) approach that reveals the magnetic susceptibility of tissue, which, e.g., indicates the presence of myelin. Cuprizone mouse models shall be used, which allow monitoring de- and remyelination. Cuprizone is a copper chelator that induces a demyelination process.

Term: 01.10.2018 – 30.09.2019

Coffin-Siris syndrom (CSS) is a neurodevelopmental disorder with cardinal features of intellectual disability and microcephaly. Mutations of transcription factor SOX11 were described as a genetic cause of CSS. In order to allow a better understanding of the pathophysiological consequences of SOX11 haploinsufficiency during human cortex development, this proposal aims to generate and analyse a SOX11+/- cerebral organoid model.

Term: 01.11.2018-31.10.2019

Tumor cells can by-pass T-cell recognition, which is a challenge in adoptive T-cell therapy. To increase the pressure on the tumor, we want to generate T cells expressing two additional tumor-specific receptors by combining stable DNA- and transient RNA-based receptor transfer. The latter of the two receptors shall have a “boost” effect in the first days of therapy by induction of direct tumor-cell killing and T-cell proliferation, leading to an effective tumor cell lysis.

Term: 01.01.2019-31.12.2019

The aim of this project is to implement and to evaluate an ultra-short echo time (UTE) pulse sequence for clinical and preclinical research at 7 Tesla, which enables non-invasive mapping of the myelin content. Image artifacts – that are common in UTE imaging – will be analyzed and corrected. The newly implemented UTE imaging technique will be applied in two proof-of-concept studies, including a mouse model of multiple sclerosis and multiple sclerosis patients.

Term: 26.03.2019 – 25.03.2020

YB-1 is expressed in chondrocytes during late embryonic stages and after birth, suggesting a crucial role of YB-1 in chondrogenesis. Little is known about signaling cascades linked to YB-1 mediating ist action. The goal of this study is to investigate YB-1-dependent pathways during chondrogenesis. Particular interest will be paid to MIA-dependent signaling (upstream) and target genes involved in transition to hypertrophy and dedifferentiation (downstream).

Term: 16.01.2019-15.01.2020

In colorectal cancer (CRC), the transcription factor ZEB1 is upregulated in tumor cells and tumor-associated macrophages. As only its tumor-promoting role in tumor cells is known, we are analyzing myeloid-specific ZEB1 knockout mice. Our preliminary data suggest that ZEB1 plays a role in macrophage polarization, intestinal inflammation and CRC growth. Here, we will explore novel functions of ZEB1 in immune homeostasis, macrophage plasticity, immune-modulation in CRC and colitis-associated CRC.

Term: 01.04.2019-31.03.2020

Physicians’ practice and opinions regarding continuous sedation until death are to be collected internationally. The German subproject aims to gain a comprehensive overview of the opinions of German palliative physicians by online survey and to link them to their professional background and experiences. The crosscultural comparison might contribute to an internationally binding definition and a more uniform treatment practice.

Term: 01.07.2019-30.06.2020

Prognostication in intracerebral hemorrhage (ICH) is biased by self-fulfilling prophecy. We will 1) validate the max-ICH Score, pooling patient data from i) single-center study from Massachusetts General Hospital (Harvard), ii) single-center UKER study, iii) multicenter RETRACE study. We will 2) conduct a prospective multicentre study with randomized controlled prognostic score usage to evaluate physician’s prognostic variability & accuracy, optimal prognostic timing, improved outcome measures.

Term: 01.04.2019-31.03.2019

Previous studies demonstrated a prognostic relevance of several molecular markers in stage T1 bladder cancer. These might optimize risk stratification and decision making with regard to immediate cystectomy or bladder sparing approach. However, these findings have not been validated yet.
The goal of the current study is to validate the association of the mRNA expression of these molecular markers with clinical and survival data in a new cohort consisting of stage T1 bladder cancer.

Term: 01.06.2019-31.05.2020

To better understand the influence of the early phase of autoimmunity of rheumatoid arthritis (RA) on joint structure, longitudinal observations of pre-RA patients are necessary. High-resolution CT is used to investigate how bone density and structure and biomechanical properties of pre-RA patients develop over time, what influence different biomarker profiles have and what bone characteristics patients developing clinical RA have.

Term: not started yet

Mitochondrial function is crucial for maintenance of the adult neural stem/progenitor cell (NSPC) pool. I found that loss of FoxO transcription factors leads to hyperproliferation and depletion of NSPCs and impairs autophagy-lysosome pathway activity. Moreover, loss of FoxOs is associated with mitochondrial dysfunction. I propose to investigate mitochondria as targets of FoxO-dependent autophago-lysosomal degradation, to establish a FoxO-mitophagy axis in the control of adult NSPC function.

Term: 01.09.2019-31.08.2020

Humans are incapable to regenerate their heart. Cardiac injury results in cardiomyocyte loss due to hypoxia and a changed mechanical micro-environment. Here we propose to determine the potential of polyploid cardiomyocytes, the majority in the adult heart, to contribute to heart repair. We propose to clarify if polyploid cardiomyocytes can be induced to proliferate or whether diploid and polyploid cardiomyocytes differ in regards to stress resistance, cell size, and mechanical properties.

Term: not started yet

The facial skin is most frequently affected by non-melanoma skin cancer (NMSC). However, the immunological profile of these tumors is still poorly understood. The anticipated ELAN project aims to address this problem by immunohistochemical investigations and may anticipate the establishment of an immunoscore which supplements the TNM classification in prognostic information and therapeutic decision making.

Term: 01.07.2019-24.08.2020

Breast cancer is the most common cancer in women worldwide. It is hypothesized that in a vicious cycle autotaxin (ATX) secreted by fat tissue influences breast cancer cells in behavior and leads to secretion of inflammatory cytokines which in turn stimulate ATX secretion of fat tissue. Radiotherapy could lead to an amplification of this effect. It is the aim of this study to evaluate the significance of the ATX/LPA-axis and the effect of radiotherapy in different breast cancer subtypes.

Term: 16.08.2019-15.08.2020

Germinal center (GC) has been described to contain hypoxic regions linked to B cell class switching. In this project, we will delineate molecular mechanism between HIF-1a-dependent glycolysis and epigenetic modification on IgA class switching region. By studying the IgA response following the C. rodentium infection, we aim to identify the link between the HIF-1a-dependent glycolytic metabolic shift and IgA class switching during microbial infection.

Term: 16.06.2019 – 15.06.2020

The focus of the present project is the investigation of Herpes simplex virus type-1 (HSV-1)-mediated modulations of the IL-6 signaling pathway in mature dendritic cells (mDCs). In particular, the underlying molecular mechanisms of reduced IL-6R?, gp130 and STAT3 expression will be analyzed on directly-infected versus uninfected bystander mDCs. Moreover, we will elucidate whether non-infectious L-particles, released from HSV-1-infected cells, are essential/sufficient to induce these modulations.

Term: 16.06.2019 – 15.06.2020

Synaptic plasticity refers to activity-dependent strengthening or weakening of synaptic transmission and underlies memory formation. It can be investigated in-vitro by repetitive network stimulation. In patients with temporal lobe epilepsy, affecting the memory-related hippocampal formation, deficits in memory can occur. We aim to investigate the link between synaptic plasticity and memory impairment by in-vitro field potential recordings from human hippocampus removed during epilepsy surgery.

Term: 16.05.2019 – 15.03.2020

The oncogenic retrovirus Human T-cell leukemia virus type 1 transmits via cell-cell contacts and viral biofilms seem to constitute a major route of virus transmission. In viral biofilms, extracellular concentrated viral particles are embedded in cocoon-like structures containing collagens (COL) of unknown composition. Here, we hypothesize that the viral transactivator Tax-1 selectively induces expression of COL4 and that COL4 is important for biofilm formation and HTLV-1 transmission.

Term: not started yet

To date, it is still obscure why in some patients with psoriasis the autoimmune process is restrained to the skin, whereas in other it extends to the joints. We will take advantage of models resembling psoriatic arthritis, with the aim of studying the joint involvement secondary to skin inflammation. The understanding and characterization of the underlying mechanisms involved in the “skin-joint axis” is pivotal for a better comprehension of the link between physical barriers and autoimmunity

Term: not started yet

In this study our goal is to analyze to what extend renal and vascular parameters correlate with histological kidney changes, especially in a population with eGFR rate of more than 60 mL/min/1.73 m². Our crossectional analysis focus on the association of abnormal vascular and renal parameters with histological renal changes. Our longitudinal analysis focus on the association of histological with renal and/or vascular parameters at baseline, with the renal outcome after kidney donation.

Term: not started yet

T cells play a major role in complications after allogeneic stem cell transplantation (allo-HSCT). In this projekt we will examine characteristics of T follicular helper cells in patients at different timepoints before and after allo-HSCT and we will correlate them with severe complications (e.g. EBV reactivation or GvHD).

Term: not started yet

18F-FDG PET/CT is as promising tool for determining treatment response in Ewing Sarcoma (EwS). Standardized uptake values as marker for metabolic tumor activity can be determined in serial scans to determine response to therapy. EwS is characetrised by circulating tumor DNA (ctDNA) that can be quantified from patients’ plasma. We intend to use 18F-FDG-PET/CT and ctDNA to determine treatment response in 20 children and adolescents suffering from EwS.

Term: not started yet

Non-classical HLA class II molecule HLA-DO largely influences the presented peptide repertoire in HLA class II. HLA-DO expression was shown to play a role in type 1 diabetes, in the generation of neutralizing antibodies to viral infections and in immune responses after allogeneic stem cell transplantation. However, the regulation of HLA-DO is distinct from other class II molecules and remains elusive. We here hypothesize that serotonin receptor signaling plays a role in the regulation of HLA-DO.

Term: 01.10.2019 – 30.09.2020

ALS is a neurological disorder molecularly manifesting in pathological aggregation of the splicing regulator TDP-43 and altered splicing in neurons (N). I aim to investigate an identified exon inclusion event in the neuromuscular junction inducer Agrin in a stem cell-based model of ALS. I use a microfluidics co-culture system of Ns and myoblasts. Additionally, in the same system, I analyze the effects of exon exclusion as seen in ALS post mortem tissue.