Project description:Human astrovirus infection is known to disrupt intestinal barrier function by increasing barrier permeabilty. However, the exact cellular mechanism(s) involved is unknown. We used microarrays to detail the global gene expression changes occuring during astrovirus infection and identify necessary cellular pathways for astrovirus pathogenesis.
Project description:The cellular response to astrovirus infection is not well defined. We used single cell RNA sequencing (scRNA-seq) to determine cellular response to astrovirus early or late in infection.
Project description:Ribosome profiling (RiboSeq) is a high-throughput sequencing technique for globally mapping the positions of translating ribosomes on the transcriptome. We infected Caco2 cells with human astrovirus 1 (HAstV1). Cells were harvested at 12 hpi and either flash frozen with no pre-treatment (NT), or pre-treated with lactimidomycin for 30 minutes followed by flash freezing (LTM). These samples where then used for ribosome profiling.
Project description:Investigation of whole genome gene expression level changes in a Salmonella enterica serovar Typhimurium UK1 delta-iacP mutant, compared to the wild-type strain. IacP is resoponsible for the secretion of virulence effector proteins via the type III secretion system, thereby contributing the virulence of S. Typhimurium. The mutants analyzed in this study are further described in Kim et al. 2011. Role of Salmonella Pathogenicity Island 1 Protein IacP in Salmonella enterica Serovar Typhimurium Pathogenesis. Infection and Immunity 79(4):1440-1450 (PMID 21263021). A chip study using total RNA recovered from two separate wild-type cultures of Salmonella enterica serovar Typhimurium UK1 and two separate cultures of a mutant strain, Salmonella enterica serovar Typhimurium UK1 delta-iacP. Each chip measures the expression level of 4,302 genes from Salmonella enterica serovar Typhimurium.
Project description:Infections of the central nervous system (CNS) in humans are on the rise due to changing environmental conditions and increase in vulnerable populations comprised of immunocompromised subjects with primary (genetic) or secondary (acquired) immunodeficiency. Many viruses take the opportunity to invade the CNS by capitalizing on impaired immunity of the host. Here we investigate neuropathogenesis of a rare CNS infection in immunocompromised patients caused by the astrovirus and show that it shares many features with another opportunistic infection of the CNS associated with human immunodeficiency virus. We show that astrovirus infects CNS neurons with a major impact on the brainstem. This leads to disrupted synaptic integrity loss of afferent innervation related to infected neurons and global impairment of both excitatory and inhibitory neurotransmission. In the settings of impaired peripheral adaptive immunity host responses to astrovirus infection are dominated by the microglia-macrophage-phagocytosis axis which may be a common compensatory defense mechanism employed by the CNS against opportunistic infections.
Project description:The study is intended to collect specimens to support the application of genome analysis technologies, including large-scale genome sequencing. This study will ultimately provide cancer researchers with specimens that they can use to develop comprehensive catalogs of genomic information on at least 50 types of human cancer. The study will create a resource available to the worldwide research community that could be used to identify and accelerate the development of new diagnostic and prognostic markers, new targets for pharmaceutical interventions, and new cancer prevention and treatment strategies. This study will be a competitive enrollment study conducted at multiple institutions.
Project description:Primary objectives: The primary objective is to investigate circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Primary endpoints: circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
