Working group Neeße

Pancreatitis and pancreatic ductal adenocarcinoma are two pancreatic disorders that pose great challenges for gastroenterologists, immunologists and oncologists likewise. In both disorders inflammatory and neoplastic insults lead to a pronounced activation of the pancreas microenvironment resulting in highly complex transcriptional and biophysical alterations through the activation of a variety of cells such as activated fibroblasts, pancreatic stellate cells, stem cells, inflammatory/immune cells, and a dynamic stromal response. The regulatory function of inflammatory transcription factors (e.g. NFAT) and secreted proteins (e.g. SPARC) within the activated pancreas microenvironment during regeneration and neoplastic transformation is not uniform and may have divergent roles, either disease promoting or restraining. The Neesse laboratory aims to investigate this exciting and emerging field in a combined basic and translational research program. To this end, a broad spectrum of (epi-) genetic, biochemical, transcriptional and pharmacological in vitro and in vivo approaches are employed to dissect the distinct roles of the pancreas microenvironment during pancreatic inflammation and neoplastic transformation. Ultimately, these findings are aimed to contribute to the design of novel and more powerful therapeutics and improved clinical management strategies for patients.

Microbiome in inflammatory and neoplastic diseases

Our laboratory investigates the composition of the human and murine microbiome in inflammatory and neoplastic diseases of the pancreas. In particular, we are interested in the role of microbes in normal acinar cells and neoplastic cells, stromal- and inflammatory cells. In particular, we investigate how microbes affect chromatin dynamics and plasticity in pancreatic cancer. Furthermore, we attempt to exploit the orointestinal microbiome as a predictive and prognostic tool in several pancreatic diseases. To investigate the microbiome, we employ 3rd generation sequencing of buccal and rectal swabs from patients, as well as tissue and body fluid samples (e.g. pseudocyst fluids) from patients and genetically engineered in vivo systems and combine these techniques with advanced molecular biology and epigenetic techniques such as ChIP-seq, ATAC-seq, and RNA-seq.

Our group has initiated two prospective clinical-translational trials that are currently enrolling patients.