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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 -
The Chloroflexi supergroup is metabolically diverse and representatives have novel genes for non-photosynthesis based CO2 fixation
(2021)bioRxivThe Chloroflexi superphylum have been investigated primarily from the perspective of reductive dehalogenation of toxic compounds, anaerobic photosynthesis and wastewater treatment, but remain relatively little studied compared to their close relatives within the larger Terrabacteria group, including Cyanobacteria, Actinobacteria, and Firmicutes. Here, we conducted a detailed phylogenetic analysis of the phylum Chloroflexota, the ...Working Paper -
Clonally expanded virus-specific CD8 T cells acquire diverse transcriptional phenotypes during acute, chronic, and latent infections
(2021)bioRxivCD8+ T cells play a crucial role in the control and resolution of viral infections and can adopt a wide range of phenotypes and effector functions depending on the inflammatory context and the duration and extent of antigen exposure. Similarly, viral infections can exert diverse selective pressures on populations of clonally related T cells. Technical limitations have nevertheless made it challenging to investigate the relationship between ...Working Paper -
Phenotypic determinism and stochasticity in antibody repertoires of clonally expanded plasma cells
(2021)bioRxivThe capacity of humoral B cell-mediated immunity to effectively respond to and protect against pathogenic infections is largely driven by the presence of a diverse repertoire of polyclonal antibodies in the serum, which are produced by plasma cells (PCs).1,2 Recent studies have started to reveal the balance between deterministic mechanisms and stochasticity of antibody repertoires on a genotypic level (i.e., clonal diversity, somatic ...Working Paper -
Comparison of RNA extraction methods for the detection of SARS-CoV-2 by RT-PCR
(2020)medRxivWorking 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 -
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 -
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 -
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 -
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