Project description:To identify the STING-dependent genes that play a role in facilitating the immunogenicity of DNA-damaged cells, normal MEFs or MEFs locking STING, cGAS, or IRF3 were irradiated. We used microarrays to detail the global programme of gene expression underlying the upregulation of several STING-induced genes in response to radiation.
Project description:Murine lung miRNAs were profiled by rodent TaqMan OpenArray after flaxseed feeding and/or radiation exposure Lung tissue was obtained 48 hours after radiation or no exposure from three animals each: flaxseed/no radiation, flaxseed/radiation, control diet/no radiation, control diet/radiation. miRNA profiles were determined by OpenArray.
Project description:Fibroblasts produce the majority of collagen in the heart and are thought to regulate extracellular matrix (ECM) turnover. However, the in vivo role of fibroblasts in structuring the basal ECM network is poorly understood. To examine the effects of fibroblast loss on the microenvironment in the adult murine heart, we generated mice with reduced fibroblast numbers and evaluated the tissue microenvironment during homeostasis and after injury. We determined that a 60-80% reduction in fibroblasts numbers did not overtly change the fibrillar collagen network but did alter the distribution and abundance of type VI collagen, a microfibrillar collagen that forms an open network with the basement membrane. In fibroblast ablated mice, myocardial infarction did not result in ventricular wall rupture, and heart function was more effectively preserved during angiotensin II/phenylephrine (AngII/PE) induced fibrosis. Analysis of cardiomyocyte contractility demonstrated weaker contractions and slower calcium release and reuptake in uninjured and AngII/PE infused fibroblast ablated animals. Moreover, fibroblast ablated hearts have a similar gene expression prolife to hearts with exercise-induced and physiological hypertrophy after AngII/PE infusion. These results suggest that hearts are resilient to a significant degree of fibroblast loss and that fibroblasts can directly impact cardiomyocyte function. Furthermore, a reduction in fibroblasts may have cardioprotective effects heart after injury suggesting that manipulation of the number of fibroblasts may have therapeutic value.
Project description:Fibroblasts produce the majority of collagen in the heart and are thought to regulate extracellular matrix (ECM) turnover. However, the in vivo role of fibroblasts in structuring the basal ECM network is poorly understood. To examine the effects of fibroblast loss on the microenvironment in the adult murine heart, we generated mice with reduced fibroblast numbers and evaluated the tissue microenvironment during homeostasis and after injury. We determined that a 60-80% reduction in fibroblasts numbers did not overtly change the fibrillar collagen network but did alter the distribution and abundance of type VI collagen, a microfibrillar collagen that forms an open network with the basement membrane. In fibroblast ablated mice, myocardial infarction did not result in ventricular wall rupture, and heart function was more effectively preserved during angiotensin II/phenylephrine (AngII/PE) induced fibrosis. Analysis of cardiomyocyte contractility demonstrated weaker contractions and slower calcium release and reuptake in uninjured and AngII/PE infused fibroblast ablated animals. Moreover, fibroblast ablated hearts have a similar gene expression prolife to hearts with exercise-induced and physiological hypertrophy after AngII/PE infusion. These results suggest that hearts are resilient to a significant degree of fibroblast loss and that fibroblasts can directly impact cardiomyocyte function. Furthermore, a reduction in fibroblasts may have cardioprotective effects heart after injury suggesting that manipulation of the number of fibroblasts may have therapeutic value.
Project description:Radiation therapy (RT) induces pleiotropic effects on the tumor immune microenvironment, but how these changes are modulated by radiation dose-fractionation is not well understood. Our in vivo data murine data suggests that while changes evoked by RT in the tumor immune compartment are largely concordant between radiation regimens, several key immunological processes are differentially regulated by radiation dose-fractionation.
Project description:Next Generation Sequencing Facilitates Quantitative Analysis Of Wild Type And Tbk1 N129D KI Murine Embryonic Fibroblast Transcriptomes
Project description:To see a possible effect of a physiological warm temperature shift (WTS, 35°C to 38.5°C) on Per2 transcription and translation in mammalian cells, we performed RNA-seq and Ribo-seq using dexamethasone-synchronized mouse embryonic fibroblast cells with or without WTS treatment at a circadain rising phase of Per2.