WorldCat Identities

Brown, Patrick O'Reilly 1954-

Overview
Works: 16 works in 23 publications in 1 language and 340 library holdings
Genres: Conference papers and proceedings 
Roles: Thesis advisor, Author
Publication Timeline
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Most widely held works about Patrick O'Reilly Brown
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Most widely held works by Patrick O'Reilly Brown
The Temporal Program of Peripheral Blood Gene Expression in the Response of Nonhuman Primates to Ebola Hemorrhagic Fever( Book )

2 editions published in 2007 in English and held by 2 WorldCat member libraries worldwide

BACKGROUND: Infection with Ebola virus (EBOV) causes a fulminant and often fatal hemorrhagic fever. In order to improve our understanding of EBOV pathogenesis and EBOV-host interactions, we examined the molecular features of EBOV infection in vivo. RESULTS: Using high-density cDNA microarrays, we analyzed genome-wide host expression patterns in sequential blood samples from nonhuman primates infected with EBOV. The temporal program of gene expression was strikingly similar between animals. Of particular interest were features of the data that reflect the interferon response, cytokine signaling, and apoptosis. Transcript levels for tumor necrosis factor-alpha converting enzyme (TACE)/alpha-disintegrin and metalloproteinase (ADAM)-17 increased during days 4 to 6 after infection. In addition, the serum concentration of cleaved Ebola glycoprotein (GP2 delta) was elevated in late-stage EBOV infected animals. Of note, we were able to detect changes in gene expression of more than 300 genes before symptoms appeared. CONCLUSION: These results provide the first genome-wide ex vivo analysis of the host response to systemic filovirus infection and disease. These data may elucidate mechanisms of viral pathogenesis and host defense, and may suggest targets for diagnostic and therapeutic development
Covalent modification of mRNAs in S. cerevisiae by Alexander Fraser Lovejoy( )

1 edition published in 2013 in English and held by 2 WorldCat member libraries worldwide

While the presence of modified nucleotides in cellular RNA has been known about for over 60 years, it is only recently that such nucleotides have become studied and mapped in mRNAs. With recent transcriptome-wide maps of N6-methyladenosine and 5-methylcytosine showing widespread mRNA modification and evolutionary conservation of many sites, it is clear that site-specific mRNA modification may represent a new level of post-transcriptional regulation of gene expression. With this in mind, we set out to map other mRNA modifications to begin to get an idea of the role they may play in gene expression. We developed a high-throughput sequencing technique that identified the first known pseudouridines in mRNA. We were able to identify the enzymes that modified a few of the top hits, as well as show that modification of at least one of the top sites is conserved throughout the fungal lineage. We have made progress toward developing an improved high-throughput sequencing technique, which could allow elucidation of a transcriptome-wide map of pseudouridines. Adapting the same technique as was used to identify mRNA pseudouridylation, we also found a few dozen possible 2'-O-methylation sites in mRNA with an interesting functional theme, though these potential modifications still need to be validated. In addition, we attempted to map and find a functional role for N6-methyladenosines in yeast undergoing meiosis, and while this failed, it led to our discovery of a target set of bound mRNAs and role in gene expression of a meiosis-specific RNA binding protein, Rim4p. The work described in this thesis identifies the third known internal, site-specific modified nucleotide in mRNA, suggesting that mRNA modifications may be more common than previously thought and may play an important, under-explored role in post-transcriptional control of gene expression
The Harvey lectures delivered under the auspices of the Harvey Society of New York( Book )

1 edition published in 2003 in English and held by 2 WorldCat member libraries worldwide

The Harvey lectures( Book )

1 edition published in 2003 in English and held by 1 WorldCat member library worldwide

The living genome( Visual )

1 edition published in 1999 in English and held by 1 WorldCat member library worldwide

Sequencing-based examination of childhood leukemogenesis : from circular RNA to single-cell genomic dissection by Charles Gawad( )

1 edition published in 2014 in English and held by 1 WorldCat member library worldwide

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and although outcomes have markedly improved over the past 50 years, it remains a leading cause of pediatric cancer-related morbidity and mortality. Studies have catalogued many of the recurrent genetic alterations that occur during the development of childhood ALL, but those investigations have not identified a definitive underlying etiology. Our current understanding is that childhood leukemogenesis begins with genetic changes in utero that interact with germline genetic predisposition to progress to ALL in a fraction of patients during childhood. Although secondary events that result in disease progression have not been identified, late exposure to common infections is a strong risk factor. To acquire a better understanding of childhood leukemogenesis, we leveraged the throughput of next-generation sequencing to globally evaluate the nucleic acid content of leukemia cells. Our initial study aimed to identify genomic structural rearrangements, as well as viral genomes or transcripts in ALL samples using RNA-seq. Through the development of novel experimental and computational methods, we surprisingly identified circular RNA isoforms are much more abundant than previously appreciated. Further work showed that they are present in normal human cells, other model organisms, and human plasma. Characterization of circular splicing of ASXL1, a gene commonly mutated in leukemia that contains a conserved circular isoform, found that the transcript is spliced into its circular isoform much less efficiently than its linear counterpart. However, we identified intronic repeat sequences, as well as exonic regions that iv are required for efficient circular splicing suggesting these molecules, which are estimated to comprise 1% of the human transcriptome, may have evolved distinct biological functions. We next used the single-allele readout of next-generation sequencing, as well as the automation of microfluidic devices to probe the genetic diversity of leukemia samples. We first discovered continued ongoing changes in the immunoglobulin locus of ALL cells using immune repertoire sequencing, which has helped improve ALL disease monitoring strategies. We then physically isolated and amplified the genomes of individual cells using microfluidics to identify mutation co-segregation patterns, as well as the clonal structures of ALL samples. With the experimental and clone-deciphering algorithms developed, we were able to determine that co-dominant clones are present in most patients, KRAS mutations occur late in disease development but are not sufficient for clonal dominance, and there are clone-specific punctuated cytosine mutagenesis events. The latter finding may lead back to the identification of a viral etiology, as the mutations have signature of APOBEC, a cytosine deaminase that is induced to provide innate anti-viral defense. Taken together, these studies have provided new paths to better understand general questions about posttranscriptional regulation, as well as the specific events that result in the development of childhood leukemias. Our deep characterization of linear and circular splicing has raised fundamental questions about the diversity of alternative splicing, as well as the importance of the resulting processed RNA in posttrancriptional regulation. Our high resolution dissection of clonal heterogeneity in childhood ALL has led to questions that could clarify the underlying etiology and pathogenesis, including the roles for APOBEC proteins, clonal symbiosis and competition, and the evolution of clonal structures that occurs after changes in selection pressure. It will take hard work, creativity, and continued technology development to decipher definitive roles of v posttranscriptional regulation and genomic heterogeneity in normal and malignant cellular biology
Methods for fabricating microarrays of biological samples by Patrick O'Reilly Brown( Book )

1 edition published in 1998 in English and held by 1 WorldCat member library worldwide

Statistical Methods for Linkage Analysis of Complex Traits from High Resolution Maps of Identity by Descent by Josée Dupuis( )

1 edition published in 1994 in English and held by 1 WorldCat member library worldwide

Studies on DNA topoisomerases by Patrick O'Reilly Brown( )

1 edition published in 1980 in English and held by 1 WorldCat member library worldwide

Evolution and coordination of gene expression through RNA-protein interactions by Gregory John Hogan( )

1 edition published in 2014 in English and held by 1 WorldCat member library worldwide

Reprogramming of a gene's expression pattern by acquisition or loss of sequences recognized by specific regulatory RNA binding proteins has the potential to be a major mechanism in the evolution of biological regulatory programs. Systematic study of orthologous Puf3 proteins across eukaryotes revealed that the RNA binding specificity is highly conserved, yet the identity and functional commonalities of their RNA targets have extensively diverged. We identified six eukaryotic lineages within which RNA targets of Puf3 orthologs have been conserved over 250-500 million years of evolution. Focusing on Puf proteins and their targets across 80 fungi, we were able to construct a parsimonious model for their evolutionary history. This history entails changes in the number of Puf genes, modifications in the RNA binding specificity of the Puf proteins, and extensive and coordinated changes in the Puf targets and, in one remarkable case, switching of hundreds of mRNA targets from Puf3 to Puf4. Binding of Puf3 to more than 200 RNAs whose protein products are predominantly involved in the production and organization of mitochondrial complexes pre-dates the origin of budding yeasts and filamentous fungi and was maintained throughout the evolution of budding yeast. In filamentous fungi, more than 150 of the ancestral Puf3 targets were gained en masse by Puf4, with one lineage maintaining both Puf3 and Puf4 as regulators and another lineage losing Puf3 as a regulator of these RNAs. Gene expression profiling and sequence analysis suggest that the regulatory consequences of Puf4 in filamentous fungi are distinct from that of Puf3 for this set of RNAs in budding yeast. In filamentous fungi, Puf4 broadened its target set to include mitochondrial genes involved in the tricarboxylic acid (TCA) cycle among other functions, and Puf3 targets in these fungi diversified, notably gaining interactions with the mRNAs encoding the electron transport chain (ETC) complex I. These and many other changes involving just this handful of Puf proteins in fungi strongly support their role in coordinating gene expression through "RNA operons" and indicate an extensive involvement of RNA binding proteins and their RNA targets in the adaptation and reprogramming of gene expression. The timing and nature of these changes are distinct from those observed at the level of transcriptional control, suggesting that RNA-protein interactions provide an additional and rich infrastructure from which gene expression can be reconfigured. Beyond the static pictures of extant gene expression programs of currently employed model organisms, identifying the changes in gene expression programs throughout evolution will provide a unique window into the make-up, logic, and malleability of gene expression, ultimately contributing to our understanding of and ability to engineer this program
 
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The Harvey lectures delivered under the auspices of the Harvey Society of New York The Harvey lectures
Covers
The Harvey lectures
Alternative Names
Patrick Brown

Patrick O. Brown Amerikaans biochemicus

Patrick O. Brown Bioquímico norteamericano

Patrick O. Brown US-amerikanischer Biochemiker

Патрик О. Браун

פטריק בראון

باتريك براون

پاتریک براون

แพทริคโอ. บราวน์

패트릭 오 브라운

パトリック・O・ブラウン

帕特里克·布朗

派屈克·布朗

Languages
English (23)