Publications

CONCLUSIONS: The qualitative results indicate that the curriculum had a broadly positive impact on residents, with specific suggestions for both scaling the curriculum as well as improving it. While no conclusions can be drawn about the specific quantitative impact of this implementation of the curriculum, these findings demonstrate an acute need for greater cancer survivorship care education for FM residents. Future initiatives iterating on expansion to multiple academic sites would be an...

Ultrasoft conductors have advanced the field of electronics by achieving a level of softness comparable to that of biological tissues. However, the inherent difference in charge carriers between conventional ultrasoft electronics (utilizing electrons) and tissues (utilizing ions) could lead to high contact impedance, hindering electronic performance for physiological signal recordings. Although ultrasoft hydrogels exhibit ionic conductivity, their high water content could limit their practical...

Leptomeningeal metastases are the most important source of morbidity and mortality for medulloblastoma patients. Radiation of the entire brain is highly effective in the treatment and/or prevention of medulloblastoma leptomeningeal metastases. Infants treated on clinical trials with focal tumor radiation recur metastatically, whereas infants treated with only chemotherapy relapse locally. In murine medulloblastoma model systems, provision of a single dose of radiation to the tumor drives...

Pancreatic ductal adenocarcinoma (PDAC) is a high-mortality cancer characterized by its aggressive, treatment-resistant phenotype and a complex tumour microenvironment (TME) featuring significant hypoxia. Bulk transcriptomic analysis has identified the "classical" and "basal-like" transcriptional subtypes which have prognostic value; however, it is not well-established how microenvironmental heterogeneity contributes to these transcriptional signatures. Here, we exploited the TRACER platform to...

CONCLUSION: These findings offer important insights into the durability and breadth of immunity following natural infection in immunocompromised transplant recipients. While heterologous neutralizing antibodies were limited, sustained CD4^(+) T-cell responses may help mitigate severe disease following exposure to JN.1-derived variants, which continue to dominate the SARS-CoV-2 landscape.

Understanding SARS-CoV-2 human protein-protein interactions (PPIs) and the host response to infection is essential for developing effective COVID-19 antivirals. However, how the ancestral virus and its variants remodel virus-host protein assemblies in various organ-specific cells and bodily fluids remains unclear. Here, we conduct 639 affinity-purifications by tagging and expressing 28 SARS-CoV-2 and spike proteins from the ancestral virus and four variants in eight cell lines representing five...

Despite advances in genome sequencing, many individuals with rare genetic disorders remain undiagnosed. Transcriptional profiling via RNA-seq can reveal functional impacts of DNA variants and improve diagnosis. We assessed blood-derived RNA-seq in the largely undiagnosed SickKids Genome Clinic cohort (n = 134), which has been subjected to multiple analyses benchmarking the utility of genome sequencing. Our RNA-centric analysis identifies gene expression outliers, aberrant splicing, and...

Characterization of DNA binding sites for specific proteins is of fundamental importance in molecular biology. It is commonly addressed experimentally by chromatin immunoprecipitation and sequencing (ChIP-seq) of bulk samples (10³-10⁷ cells). We have developed an alternative method that uses a Chromatin Antibody-mediated Methylating Protein (ChAMP) composed of a GpC methyltransferase fused to protein G. By tethering ChAMP to a primary antibody directed against the DNA-binding protein of...

Fungal infections cause more than 2.5 million deaths a year. Due to emerging antifungal drug resistance, novel strategies are urgently needed to combat life-threatening fungal diseases. Here, by screening a collection of 5297 compounds derived from three chemical libraries, we demonstrate that the antibacterial agent colistin (COL) can potentiate the fungistatic echinocandins caspofungin (CAS) and anidulafungin, as well as the structurally distinct cell wall targeting antifungal ibrexafungerp...

Recurrent mutations in the third base of U1 spliceosomal RNA responsible for marked splicing and expression abnormalities have been described in chronic lymphocytic leukemia (CLL) and some solid tumors. However, the clinical significance of these mutations in large and independent CLL cohorts as well as their presence in other B-cell neoplasms is unknown. Here we characterized U1 mutations in 1670 CLL and 363 mature B-cell lymphomas. We confirmed that the g.3A>C U1 mutation is found in 3.5% of...

Despite its versatility and high chemical specificity, conventional nuclear magnetic resonance (NMR) spectroscopy is limited in measurement throughput due to the need for high-homogeneity magnetic fields, necessitating sequential sample analysis, and expensive devices. Here, we propose a multichannel NMR device that addresses these limitations by leveraging the zero-to ultralow-field (ZULF) regime, where simultaneous detection of multiple samples is carried out via an array of compact optically...

Gene duplication is common across the Tree of Life and contributes to genomic robustness. In this study, we examined changes in the subcellular localization and abundance of proteins in response to the deletion of their paralogs originating from the whole-genome duplication event, which is a largely unexplored mechanism of functional divergence. We performed a systematic single-cell imaging analysis of protein dynamics and screened subcellular redistribution of proteins. We find that 20% of...

Here, we announce the closed genome of Solidesulfovibrio sp. DCME, assembled from metagenomic sequencing of an anaerobic dichloromethane mineralizing enrichment culture. The Solidesulfovibrio genus is known to cycle hydrogen, a key process for facilitating dichloromethane mineralization, which nominates this microbe as an important player in its microbial community.

CONCLUSIONS: Results illustrate importance of evaluating neuropsychological pathways with precision, efficiency and caregiver-partners in mind.

Brassica napus (canola; AnAnCnCn) contains both complete diploid genomes from its progenitors B. rapa (An) and B. oleracea (Cn). Despite growing knowledge of the gene expression landscape of the B. napus seed, little is known about subgenome bias underpinning the development of specific cells and tissues across the seed lifecycle. Here, we present a large-scale transcriptome atlas of the B. napus seed, including both the maternal seed coat and filial embryo and endosperm subregions. We report on...

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Developmental origins and their associations with lineage plasticity and treatment response in B-cell progenitor acute lymphoblastic leukemia (B-ALL) are mostly unexplored. Here, we integrated single-cell transcriptome sequencing (scRNA-seq) of 89 B-ALL samples with a single-cell atlas of normal human B cell development incorporating functional and molecular assays. We observed subtype- and sample-dependent correlation with normal developmental stage, with intra-subtype and intra-patient...

Specific and biologically informed treatments for medulloblastoma, especially for the highly lethal TP53-mutant SHH subgroup, remain elusive, where radiotherapy is the primary treatment modality. Leveraging genome-wide CRISPR-Cas9 dropout screening in combination with lethal doses of radiotherapy, we identify loss of p53 as the main driver of radiation resistance in SHH medulloblastoma. A negative-selection CRISPR-Cas9 screen across multiple models of Trp53-deficient SHH medulloblastoma reveals...

Bipolar disorder is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 bipolar disorder risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci and prioritized 17 likely causal SNPs for bipolar disorder. We mapped these SNPs to genes and investigated their likely functional consequences by integrating variant annotations, brain...

CONCLUSION: Significantly more dysregulated proteins and biological pathways were found in males than in females with PsA. The identified proteins and pathways offer potential new targets for sex-based research in PsA.