Helicobacter pylori (H. pylori) is the major risk factor for the development of gastric cancer. Our laboratory has reported that the Sonic Hedgehog (Shh) signaling pathway is an early response to infection that is fundamental to the initiation of H. pylori-induced gastritis. H. pylori also induces programmed death ligand 1 (PD-L1) expression on gastric epithelial cells, yet the mechanism is unknown. We hypothesize that H. pylori-induced PD-L1 expression within the gastric epithelium is mediated by the Shh signaling pathway during infection. To identify the role of Shh signaling as a mediator of H. pylori-induced PD-L1 expression, human gastric organoids generated from either induced pluripotent stem cells (HGOs) or tissue (huFGOs) were microinjected with bacteria and treated with Hedgehog/Gli inhibitor GANT61. Gastric epithelial monolayers generated from the huFGOs were also infected with H. pylori and treated with GANT61 to study the role of Hedgehog signaling as a mediator of induced PD-1 expression. A patient-derived organoid/autologous immune cell co-culture system infected with H. pylori and treated with PD-1 inhibitor (PD-1Inh) was developed to study the protective mechanism of PD-L1 in response to bacterial infection. H. pylori significantly increased PD-L1 expression in organoid cultures 48 hours post-infection when compared to uninfected controls. The mechanism was cytotoxic associated gene A (CagA) dependent. This response was blocked by pretreatment with GANT61. Anti-PD-L1 treatment of H. pylori infected huFGOs, co-cultured with autologous patient cytotoxic T lymphocytes and dendritic cells, induced organoid death. H. pylori-induced PD-L1 expression is mediated by the Shh signaling pathway within the gastric epithelium. Cells infected with H. pylori that express PD-L1 may be protected from the immune response, creating premalignant lesions progressing to gastric cancer.
The Retrosplenial Cortex (RSC) has a persistent role in the establishment of spatial and contextual memory, with also the connections between visuo-spatial association cortices. The RSC’s ability to form afferent and efferent connections with the Parahippocampal areas of the brain allow it to be another prime location in the brains of both rodents and humans where multiple cues are linked together in memory formation, storage and retrieval of Long Term Memories. Due to the high nature of memory formation and retrieval, the RSC has become a section of the brain that in recent years has been more heavily focused on for the research of Alzheimer’s and Dementia. The RSC has not been examined fully in previous studies with examination of the expression of the apolipoprotein E (APOE) gene along with other genetic and regulatory factors. There are 3 major alleles of the APOE gene (APOE2, APOE3, and APOE4), with APOE4 having the greatest risk for AD. In this research, I identify the relative connection between DEK the proto-oncogene and APOE3 and APOE4 in a rodent model, looking specifically at the RSC and how it affects spatial memory with an induced model of chronic stress.
This program is meant to batch process ELISA standard curve data to generate Levey-Jennings control charts and report values that fall outisde of 2 and 3 standard deviations of the mean. The Instruction Manual contains a detailed guide on usage.