Browsing by Author "Pillai, Dylan R."
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Item Open Access Characterizing GATA6+ cells in the kidney(2024-09-13) Belay, Sisay Getie; Muruve, Daniel A.; Chun, Justin; Pillai, Dylan R.Globally, acute kidney injury (AKI) and chronic kidney disease (CKD) cause an estimated 13 million and 700 million cases/year, and 1.7 million and 1.2 million deaths/year, respectively. Kidney disease is the result of many different insults. Kidney injury promotes the recruitment and proliferation of different leukocyte populations, including macrophages to the kidney that play a major role in disease pathogenesis. Recruitment of resolution and reparative macrophages induce anti-inflammatory responses and promote kidney repair, but the characteristics of these cell populations are not clearly defined. GATA6+ macrophages had been reported to facilitate tissue repair following injury in organs other than the kidney. However, whether GATA6+ macrophages are resolution and repair macrophages in the kidney is not known. Using immunofluorescence imaging, flow cytometry, and nCounter transcriptome techniques, we assessed GATA6+ cells in normal and diseased kidney of mouse and human while probing common tissue macrophage markers specifically CD206+ and CD163+ as a benchmark. We showed that both CD206+ and CD163+ macrophages were detectable in normal and diseased mouse and human kidney. In mouse, both CD206+ and CD163+ macrophages were upregulated in various kidney compartments especially during CKD. Whereas in human, CD206+ and CD163+ macrophages appeared to be resident in the kidney and upregulated in diseased states. Using the same technique, significant population of GATA6+ cells were identified in mouse and human kidney particularly during CKD. GATA6+ cells were mainly localized in the tubulointerstitial area of the kidney cortex. In mouse and human kidney, the majority of GATA6+ cells did not co-express common leukocyte/macrophage markers. Conversely, in mouse and human CKD, GATA6+ cells mostly co-expressed the stromal cell marker αSMA. Using nCounter transcriptome profile of mouse samples, GATA6+ cells represented a distinct non-immune cell population that expressed genes associated with stromal cell identity, inflammation regulation, angiogenesis and collagen biosynthesis. The role of GATA6+ cells in CKD will require further exploration to unravel specific pathological and/or repair mechanisms that may lead to improved management of kidney disease.Item Open Access Comparative Genomic Analyses of Streptococcus pseudopneumoniae Provide Insight into Virulence and Commensalism Dynamics(PLoS, 2013-06-19) Shahinas, Dea; Thornton, Christina S.; Tamber, Gurdip Singh; Arya, Gitanjali; Wong, Andrew; Jamieson, Frances B.; Ma, Jennifer H.; Alexander, David C.; Low, Donald E.; Pillai, Dylan R.Item Open Access Development and application of ultra-sensitive tools for the detection of malaria(2020-01) Mohon, Md Abu Naser; Pillai, Dylan R.; Wasmuth, James D.; Parkins, Michael D.The goal to eliminate malaria has been challenged by the lack of accurate diagnostic tools to identify symptomatic, asymptomatic, and drug-resistant malaria carriers. In this dissertation, we have shown the potential of the Loop-mediated Isothermal Amplification (LAMP)-based diagnostic approaches to be a powerful tool available for malaria elimination. We have validated the combination of the Non-instrumented Nucleic Acid (NINA) platform heater (PATH, Seattle) with a commercial LAMP kit (LoopAmp malaria Pan/Pf detection kit), with a view to deploying it in extremely resource-limited settings in the future. An ultrasensitive (US)-LAMP assay was also developed and validated to identify asymptomatic malaria reservoirs. Moreover, a novel strategy for detecting single nucleotide polymorphisms (SNPs) by the LAMP method was designed and deployed for spotting artemisinin resistance in P. falciparum. We conclude that the NINA-LAMP assay can be a convenient test for detecting symptomatic malaria cases with a sensitivity of 100% and specificity of 98.6% compared to the gold standard nested PCR. Additionally, the US-LAMP assay was able to achieve a limit of detection (LOD) between 25 to 100 parasites/mL from dried blood spots. We have also found that the overall prevalence of asymptomatic malaria was 22.1% in the Gambella region of Ethiopia, detected by the US-LAMP assay. The sensitivity and the specificity of the US-LAMP assay were 92.6% and 97.1%, respectively compared to an ultrasensitive quantitative reverse transcriptase PCR. Additionally, the SNP-LAMP assay was 100% sensitive and 97.3% specific to identify the C580Y mutation in the kelch 13 propeller gene, which is known as the major genetic determinant of artemisinin resistance in Southeast Asia. Furthermore, we conclude that artemisinin resistance-linked kelch 13 propeller mutations are absent in the Bangladeshi P. falciparum isolates. However, two cases of the A578S SNP in the kelch 13 propeller gene were found in those P. falciparum isolates, although this SNP was not associated with artemisinin resistance. In conclusion, as the LAMP-based diagnostic approaches are simple, low-cost, and accurate compared to currently available nucleic acid tests, they can be used at different aspects to diagnose malaria and expedite elimination.Item Open Access False positive malaria rapid diagnostic test in returning traveler with typhoid fever(BioMed Central, 2014-06-09) Meatherall, Bonnie; Preston, Keith; Pillai, Dylan R.Item Open Access Population-Based Laboratory Surveillance of Imported Malaria in Metropolitan Calgary, 2000–2011(PLoS ONE, 2013-04-15) Lee, Clara S.; Gregson, Daniel B.; Church, Deirdre; Laupland, Kevin B.; Eckhardt, Rose; Ross, Terry; Chan, Wilson; Pillai, Dylan R.Item Open Access A Purine Analog Synergizes with Chloroquine (CQ) by Targeting Plasmodium falciparum Hsp90 (PfHsp90)(Public Library of Science (PLoS), 2013-09-30) Shahinas, Dea; Folefoc, Asongna; Taldone, Tony; Chiosis, Gabriela; Crandall, Ian; Pillai, Dylan R.