A caspase-1 inhibitor was shown to decrease not only caspase-1-mediated cleavage of HTT at 572, but at the 586 caspase-6 site as well. When we blocked proteolysis or cleavage at this site in cell culture, we found that the mutant protein formed significantly less aggregates and that the half-life of the protein significantly decreased, suggesting it is cleared from the cell faster. Therefore, targeting caspase-1 could be beneficial two-fold; by inhibiting the new site of cleavage at 572 as well as by inhibiting activation of caspase-6 through caspase-1 leading to decreased 586 cleavage.
Millions of clinical specimens are stored in the form of formalin-fixed paraffin-embedded (FFPE) samples. The capacity to tap into these samples is crucial for NGS analysis; however, there are two major challenges with FFPE samples. First, the extraction and sample preparation methods are tedious. Second, data quality is degraded following formalin fixation, storage and purification. The authors showed that among the sequencing artifacts are chimeric reads that appear to be derived from non-contiguous portions that align to both the ‘Watson’ and ‘Crick’ strands of the reference genome.
Plant-associated microbial communities improve plant health by helping plants defend against pathogens and helping with nutrient uptake. Like those microbes that colonize the human gut, plant root, or “rhizosphere” communities must evade plant immunity and use host-derived nutrients. To determine how members of the plant microbiome evades plant immunity, we use a model system consisting of the beneficial bacterium Pseudomonas fluorescens and the model host Arabidopsis thaliana. Using this system, we performed a genome-wide screening, using a technique called “Tn-Seq” to identify bacterial genes required to evade the plant immune system.
Granzyme K (GzmK) is occasionally referred to as an ‘orphan granzyme’ due to the lack of knowledge pertaining to its function in health and disease. To our knowledge, the present study, published in J. Invest. Dermatol., is the first study to ever examine the role of GzmK in any model of injury and inflammation and only documented study looking at a role for GzmK in skin. In the study, lead author Dr. Chris Turner along with Dr. Matt Zeglinski, post-doctoral fellows in Dr. David Granville’s laboratory, and other co-authors, investigated the role of GzmK in inflammation and repair in a murine model of acute cutaneous wound healing.
Decades of lack of progress in treating many fatal malignancies of the blood-forming system is commanding interest in new approaches. Targeting early events in the leukemogenic process has long been recognized as likely to offer the information required for these diseases. Analysis of the representation of different mutations in the leukemic cells from individual patients offers a retrospective method to…
TIM-3 is an immune biomarker that is currently targeted by new immunotherapy drugs. Our study reports the first large-scale evaluation of TIM-3 expression based on our examination of nearly 4,000 breast cancers from the province of British Columbia. We report that TIM3 is present in more than a quarter of patients with a basal-like breast cancer, an aggressive cancer type with no targeted therapy. The findings from our publication imply that patients with basal-like breast cancers can potentially be amenable to immunotherapies targeting TIM-3.
Each year, about 1 in 10 babies worldwide are born before the pregnancy has reached full term. Using samples of tissue collected from donated placentas from preterm births with and without inflammation, we examined DNA methylation, a chemical mark on DNA that is associated with how genes are turned on and off in the cell. We were able to identify unique DNA methylation changes in the placenta associated with inflammation in preterm birth pregnancies.
Genomic rearrangements in the MYC locus occur in ∼12% of lymphomas with diffuse large B-cell lymphoma (DLBCL) morphology and are associated with inferior outcome. Previous studies exploring MYC rearrangements have primarily used fluorescence in situ hybridization (FISH) assays to characterize break-apart status but have rarely examined breakpoint location, and in some cases have not examined partner identity. We performed targeted sequencing of MYC, BCL2, BCL6, and the…
Calmodulin (CaM) represents one of the most conserved proteins among eukaryotes and is known to bind and modulate more than a 100 targets. Recently, several disease-associated mutations have been identified in the CALM genes that are causative of severe cardiac arrhythmia syndromes. Although several mutations have been shown to affect the function of various cardiac ion channels, direct structural insights into any…
Our study found that many of the common DNA methylation alterations found in prostate cancer are present in luminal cells from both cancer and normal tissues. These changes are not necessarily cancer-specific, and are likely due to the bias associated with analyzing tissues in bulk, where most cancer cells have luminal-like features. We derived two cancer-specific and phenotype-independent DNA methylation signatures: one specific to prostate cancer luminal cells, and one composed of alterations present in both luminal and basal cancer cells.