Project description:the genetic inactivation of Khk-C enhanced the survival of KPC-driven PDAC model even in absence of high fructose diet. Moreover Khk-C knock out decreased the viability of KPC organoids and cancer cells, the migratory capability of PDAC cells in vitro and the growth of KPC cells in vivo in a cell autonomous manner.
Project description:Pancreatic cancer is among the deadliest cancers that affects almost 54,000 patients in United States alone, with 90% of them succumbing to the disease. Lack of early detection is considered to be the foremost reason for such dismal survival rates. Our study shows that resident gut microbiota is altered at the early stages of tumorigenesis much before development of observable tumors in a spontaneous, genetically engineered mouse model for pancreatic cancer. In the current study, we analyzed the microbiome of in a genetic mouse model for PDAC (KRASG12DTP53R172HPdxCre or KPC) and age-matched controls using WGS at very early time points of tumorigenesis. During these time points, the KPC mice do not show any detectable tumors in their pancreas. Our results show that at these early time points, the histological changes in the pancreas correspond to a significant change in certain gut microbial population. Our predictive metabolomic analysis on the identified bacterial species reveal that the primary microbial metabolites involved in progression and development of PDAC tumors are involved in polyamine metabolism.
Project description:ASoC variants are prevalent and cell type-specific ASoC variants were over-represented in intergenic regions and active enhancers. The collection includes ATAC-Seq and RNA-Seq data that were taken from human iPS cells and their derived neuronal cells (neural progenitor cells, cortical glutamatergic neurons, GABAergic neurons, and dopaminergic neurons).
