Pancreatic cancer initiation through IPMN precursor lesions modelled in GNAS-mutated human pluripotent stem cell derived ductal organoids
Pancreatic cancer is one of the leading causes of cancer-related deaths, which can be partly attributed to the lack of measures for early disease detection and of curative treatment.
Developing novel humanized monoclonal antibodies with ultra-long CDRs inspired by nature to target the gp120 of HIV
Immunoglobulin G (IgG) antibodies are essential components of our immune system. IgGs recognize and bind antigens with their hypervariable complementarity-determining regions (CDRs). Human IgGs have only relatively short CDRs, which limits their ability to recognize some antigens like the human immunodeficiency virus (HIV). Interestingly, bovine antibodies can have exceptionally long and complex CDRs, allowing them to bind HIV proteins like the gp120 with high affinity.
Longitudinal assessment of cerebral microstructural damage and resulting cognitive deficits in relapsing-remitting multiple sclerosis
Multiple Sclerosis (MS) is an autoimmune disease affecting the brain and the spinal cord. Conventional MRI imaging mainly assesses the lesion load - the "tip of the iceberg" of cerebral tissue damage in MS. Up to now, microstructural tissue changes outside the lesions are not taken into account in clinical studies targeting MS. This project aims to quantify longitudinal changes in normal appearing cerebral tissue in MS patients using quantitative MRI techniques and to assess the relationship of tissue remodelling over time with changes of the clinical / cognitive status.
Development of a biosignature for the chronic rhinosinusitis without nasal polyps
Goal of the project is the development of a non-invasive biosignature for the chronic rhinosinusitis without polyps. The pathophysiology of the disease will be investigated and a model for monitoring disease severity will be developed.
Potential protein biomarkers will be identified using a multiplexed approach and molecular biological validation methods. Due to the non-invasive design a painless and repetitive sampling is possible. A prospective study will be performed and it will be validated if the biosignature can monitor disease severity and therapeutic effects.
Neurocognitive mechanisms of impaired reward-related decision-making in schizophrenia
Schizophrenia is a chronic psychiatric disorder that comprises – apart from psychotic symptoms like delusions and hallucinations – also symptoms such as lack of motivation and cognitive deficits (e.g., impairments of decision-making or memory). Deficits of motivation and cognition contribute greatly to patients’ impaired everyday functioning, but current medication has only little effect on them.
Die funktionelle Rolle von tumor-spezifischen B-Zellantworten in präklinischen Modellen der Immun Checkpoint Therapie
Immune checkpoint inhibition demonstrated breakthrough therapeutic efficacy in cancer. Nevertheless, there is urgent need for deciphering the mode of action of checkpoint inhibition, since the majority of patients does not benefit from these therapies. Although B cells play a major part in activation of a tumor-directed immune response, their role in checkpoint therapies has largely been neglected. In this project, we aim to study the functional impact of B cells on the efficacy of checkpoint inhibition in pancreatic and gastric cancer.
Investigation of the role of ARHGEF6 as a potential novel monogenic cause of congenital anomalies of the kidney and urinary tract
The number of patients with chronic kidney disease (CKD) is on the rise and represents a global health burden. Treatment options for patients with end-stage renal disease are limited to dialysis and renal transplantation. Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common causes of end-stage renal disease in childhood and have a monogenic causation in ~20% of the cases. Dr. Klämbt discovered mutations in the gene ARHGEF6 in pediatric patients with CAKUT using whole exome sequencing.
Die Rolle des Tumormikromilieus bei der T-Zell-Erschöpfung und Immunität von malignen ZNS Tumoren
Glioblastomas are malignant tumors of the central nervous system which lead to death within 1-2 years. Promising immunotherapeutic approaches failed to improve survival in glioblastomas. Although the reasons are not completely understood yet, it is assumed that the tumor environment is a barrier for immune cells. In the funded research project, we aim is to investigate the mechanism by which the inactivation of the immune system occurs, which cells are engaged in this process and how this inactivation can be prevented.
Enhancement of antitumor immunogenecity in pancreatic cancer via intrapancreatic transplantation of tumor lysate-pulsed dendritic cells
Pancreatic cancer (PCa) is characterized by its highly immunosuppressive microenvironment and resistance to immune-based therapies. Recent studies demonstrated that dendritic cells (DC) may potentiate the effect of immune checkpoint inhibitors (ICI) in many solid malignancies. In this context, tertiary lymphoid structures (TLS) represent privileged sites for presentation of tumor antigens by DCs and subsequent activation of T cell and B cell responses.