Dye Lab Research and Publications

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Elucidating how Merkel Cell polyomavirus causes Merkel Cell Carcinoma​

Merkel Cell Carcinoma (MCC) is an aggressive skin cancer that is three times deadlier than melanoma. In 2008, it was found that 80% of MCC cases are caused by the genomic integration of a novel polyomavirus, Merkel Cell Polyomavirus (MCPyV) and the expression of its small and truncated large tumor antigens (ST and LT-t, respectively). MCPyV belongs to a family of human polyomaviruses; however, it is the only one with a clear association to cancer. However, polyomaviruses in other species, such as Simian Vacuolating Virus 40 (SV40) has been shown to be oncogenic in rodents. The Dye lab has utilized many models to identify ST to be responsible for transformation by MCPyV, which is in contrast to SV40, in which LT is the dominant transforming protein. Furthermore, the ST antigen of MCPyV is uniquely transforming among human polyomaviruses, as the ST antigens of Human Polyomavirus 7 (HPyV7) and Trichodysplasia Spinulosa Polyomavirus (TSPyV) were found to be non-transforming and not associated with cancer. Therefore, instead of using a similarity approach between MCPyV and SV40 to identify how MCPyV ST causes cancer, we have employed a novel dissimilarity approach by comparing the differences between MCPyV, TSPyV and HPyV7 ST. In doing so, we have identified MCPyV ST to uniquely localize to the nucleus, despite the absence of a canonical nuclear localization signal (NLS), suggesting that MCPyV ST employs a novel approach to accomplish nuclear localization. Furthermore, it has been found that the nuclear localization of MCPyV ST is necessary for many of its transforming properties. Current research aims to investigate the mechanism of MCPyV ST nuclear localization and its role in cellular transformation. ​

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Using Wastewater as a means of SARS-CoV-2 pandemic tracking and viral evolution monitoring ​

On May 24, 2023, approximately 3.5 years into the pandemic, the World Health Organization (WHO) declared the end of the COVID-19 global health emergency. However, as there are still ∼3000 COVID-19 deaths per day in May 2023, robust surveillance systems are still warranted to return to normalcy in times of low risk and respond appropriately in times of high risk. The different phases of the pandemic have been defined by infection numbers and variants, both of which have been determined through clinical tests that are subject to many biases. Unfortunately, the end of the COVID-19 emergency threatens to exasperate these biases, thereby warranting alternative tracking methods. We hypothesized that wastewater surveillance could be used as a more accurate and comprehensive method to track SARS-CoV-2 in the post-emergency pandemic period (PEPP). SARS-CoV-2 was quantified and sequenced from wastewater between June 2022 and March 2023 to research the anticipated 2022/23 winter surge. However, in the 2022/23 winter, there was lower-than-expected SARS-CoV-2 circulation, which was hypothesized to be due to diagnostic testing biases but was confirmed by our wastewater analysis, thereby emphasizing the unpredictable nature of SARS-CoV-2 surges while also questioning its winter seasonality. Even in times of low baseline circulation, we found wastewater surveillance to be sensitive enough to detect minor changes in circulation levels ∼30–46 days prior to diagnostic tests, suggesting that wastewater surveillance may be a more appropriate early warning system to prepare for unpredictable surges in the PEPP. Furthermore, sequencing of wastewater detected variants of concern that were positively correlated with clinical samples and also provided a method to identify mutations with a high likelihood of appearing in future variants, necessary for updating vaccines and therapeutics prior to novel variant circulation. Together, these data highlight the effectiveness of wastewater surveillance in the PEPP to limit the global health burden of SARS-CoV-2 due to increases in circulation and/or viral evolution.​

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