A5091122255- Pancreatic function and diabetes
- Pancreatic and Hepatic Oncology Research
- Pancreatitis Pathology and Treatment
- Epigenetics and DNA Methylation
- Diabetes and associated disorders
- Diabetes Management and Research
- Renal and related cancers
- Neuroendocrine Tumor Research Advances
- Cancer-related gene regulation
- Peptidase Inhibition and Analysis
- Genetics and Neurodevelopmental Disorders
- Cancer Genomics and Diagnostics
- Ubiquitin and proteasome pathways
- Chromatin Remodeling and Cancer
- Chronic Lymphocytic Leukemia Research
Technical University of Munich
2024
University of California, San Francisco
2016-2021
Max Planck Institute of Immunobiology and Epigenetics
2017-2018
Pancreatic β cells are highly specialized to regulate systemic glucose levels by secreting insulin. In adults, increase in β-cell mass is limited due brakes on cell replication. contrast, proliferation robust neonatal that functionally immature as defined a lower set point for glucose-stimulated insulin secretion. Here we show and immaturity linked tuning expression of physiologically relevant, non-oncogenic c-Myc. Adult induced replicate adopt gene metabolic profiles resembling those...
To date, it remains largely unclear to what extent chromatin machinery contributes the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single-cell transcriptomics mine for evidence dysregulation in type 2 diabetes. We find two chromatin-state signatures that track β cell dysfunction mice humans: ectopic activation bivalent Polycomb-silenced domains loss expression at an epigenomically unique class lineage-defining genes. cell-specific Polycomb...
Aberrant activation of embryonic signaling pathways is frequent in pancreatic ductal adenocarcinoma (PDA), making developmental regulators therapeutically attractive. Here we demonstrate diverse functions for and duodenal homeobox 1 (PDX1), a transcription factor indispensable pancreas development, the progression from normal exocrine cells to metastatic PDA. We identify critical role PDX1 maintaining acinar cell identity, thus resisting formation intraepithelial neoplasia (PanIN)-derived...
Chromatin remodeler Brahma related gene 1 (BRG1) is silenced in approximately 10% of human pancreatic ductal adenocarcinomas (PDAs). We previously showed that BRG1 inhibits the formation intraductal mucinous neoplasm (IPMN) and IPMN-derived PDA originated from cells. However, role intraepithelial neoplasia–derived (PanIN-derived) acinar cells remains elusive. Here, we found exclusive elimination Brg1 Ptf1a-CreER; KrasG12D; Brg1fl/fl mice impaired acinar-to-ductal metaplasia (ADM) PanIN...
To study disease development, an inventory of organ's cell types and understanding physiologic function is paramount. Here, we performed single-cell RNA-sequencing to examine heterogeneity murine pancreatic duct cells, pancreatobiliary intrapancreatic bile cells. We describe epithelial-mesenchymal transitory axis in our three subpopulations identify osteopontin as a regulator this fate decision well human dedifferentiation. Our results further functional within by elucidating role for...
ABSTRACT Lineage tracing using genetically engineered mouse models is an essential tool for investigating cell-fate decisions of progenitor cells and biology mature cell types, with relevance to physiology disease progression. To study development, inventory organ’s types understanding physiologic function paramount. Here, we performed single-cell RNA sequencing examine heterogeneity murine pancreatic duct cells, pancreatobiliary intrapancreatic bile cells. We describe epithelial-mesenchymal...
SUMMARY Chromatin is the physical template that stabilizes and specifies transcriptional programs. To date, it remains largely unclear to what extent chromatin machinery contributes susceptibility progression of complex diseases. Here, we combined deep epigenome mapping with single cell transcriptomics mine for evidence dysregulation in type-2 diabetes. We identify two chromatin-state signatures track trajectory β-cell dysfunction mice humans: ectopic activation bivalent Polycomb-domains a...
Abstract Aberrant epigenetic regulation is a hallmark of pancreatic cancer. Since changes in histone methylation are potentially reversible, they present an attractive target for therapeutic intervention. Kdm6a and Kdm6b belong to family demethylases specific lysine 27 3 have been implicated multiple types cancer, including ductal adenocarcinoma (PDA). We gathered data from the extensive investigation mouse model PDA which either or both deleted with concomitant activation oncogenic KrasG12D...