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High-throughput identification of RNA localization elements reveals a regulatory role for A/G rich sequences
(2021)bioRxivHundreds of RNAs are enriched in the projections of neuronal cells. For the vast majority of them, though, the sequence elements within them that regulate their localization are unknown. To identify RNA elements capable of directing transcripts to neurites, we designed and deployed a massively parallel reporter assay that tested the localization regulatory ability of thousands of sequence fragments drawn from endogenous mouse 3′ UTRs. We ...Working Paper -
Spatiotemporal proteomics uncovers cathepsin-dependent host cell death during bacterial infection
(2018)bioRxivImmune cells need to swiftly and effectively respond to invading pathogens. This response relies heavily on rapid protein synthesis and accurate cellular targeting to ensure pathogen destruction. In return, pathogens intercept this response to ensure their survival and proliferation. To gain insight into this dynamic interface, we combined click-chemistry with pulsed stable isotope labeling of amino acids (pSILAC-AHA) in cell culture to ...Working Paper -
Comparison of RNA extraction methods for the detection of SARS-CoV-2 by RT-PCR
(2020)medRxivWorking Paper -
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Multi-platform discovery of haplotype-resolved structural variation in human genomes
(2018)bioRxivThe incomplete identification of structural variants from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long- and short-read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three human parent-child trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We ...Working Paper -
Defining the Pandemic at the State Level: Sequence-Based Epidemiology of the SARS-CoV-2 virus by the Arizona COVID-19 Genomics Union (ACGU)
(2020)medRxivIn December of 2019, a novel coronavirus, SARS-CoV-2, emerged in the city of Wuhan, China causing severe morbidity and mortality. Since then, the virus has swept across the globe causing millions of confirmed infections and hundreds of thousands of deaths. To better understand the nature of the pandemic and the introduction and spread of the virus in Arizona, we sequenced viral genomes from clinical samples tested at the TGen North Clinical ...Working Paper -
Cardiovascular responses to antigravity muscle loading during head-down tilt at rest and after dynamic exerrcises
(2018)bioRxivThe physiological processes underlying hemodynamic homeostasis can be modulated by muscle activity and gravitational loading. The effects of antigravity muscle activity on cardiovascular regulation has been observed during orthostatic stress. Here, we evaluated such effects during head-down tilt (HDT). In this posture, the gravitational gradient along the body is different than in upright position, leading to increased central blood volume ...Working Paper -
Distinct microRNA signature in human serum and germline after childhood trauma
(2020)medRxivTraumatic experiences during childhood can persistently alter mental and physical health in humans and have been implicated in transmission of symptoms to the progeny in animal models. Molecular evidence from these models implicates epigenetic/non-genetic factors, such as microRNAs (miRNAs), in the expression of trauma-induced symptoms and their transmission to the offspring. To confirm these findings in humans, we assembled three cohorts ...Working Paper -
The Physiological Landscape and Specificity of Antibody Repertoires
(2021)bioRxivDiverse antibody repertoires spanning multiple lymphoid organs (e.g., bone marrow, spleen, lymph nodes) form the foundation of protective humoral immunity. Changes in their composition across lymphoid organs are a consequence of B-cell selection and migration events leading to a highly dynamic and unique physiological landscape of antibody repertoires upon antigenic challenge (e.g., vaccination). However, to what extent B cells encoding ...Working Paper