1,296 research outputs found
Elite male faculty in the life sciences employ fewer women
No full textWomen make up over one-half of all doctoral recipients in biology-related fields but are vastly underrepresented at the faculty level in the life sciences. To explore the current causes of women’s underrepresentation in biology, we collected publicly accessible data from university directories and faculty websites about the composition of biology laboratories at leading academic institutions in the United States. We found that male faculty members tended to employ fewer female graduate students and postdoctoral researchers (postdocs) than female faculty members did. Furthermore, elite male faculty—those whose research was funded by the Howard Hughes Medical Institute, who had been elected to the National Academy of Sciences, or who had won a major career award—trained significantly fewer women than other male faculty members. In contrast, elite female faculty did not exhibit a gender bias in employment patterns. New assistant professors at the institutions that we surveyed were largely comprised of postdoctoral researchers from these prominent laboratories, and correspondingly, the laboratories that produced assistant professors had an overabundance of male postdocs. Thus, one cause of the leaky pipeline in biomedical research may be the exclusion of women, or their self-selected absence, from certain high-achieving laboratories
Abstract 390: Identification and characterization of survival-associated genomic features across tumor types
No full textAbstract
The basic biology that differentiates a primary cell from a transformed cell has been elucidated over the past several decades. Mutations in a limited number of oncogenes and tumor suppressors free the cell from growth-inhibitory checkpoints and allow proliferation in the absence of external stimuli, leading to tumor formation. Yet, primary tumors themselves are rarely deadly: greater than 90% of cancer mortality results from metastasis. What drives metastasis, and, more broadly, what distinguishes a lethal cancer from one with a favorable prognosis, is poorly understood.
To address this question, we have performed a comprehensive meta-analysis on genomic data from primary tumors that are linked to patients’ clinical outcomes. Utiliizing data from >20,000 patients, we have identified protein-coding genes, lncRNAs, miRNAs, methylation sites, and CNVs in primary tumors that are significantly associated with patient prognosis across cancer types. Multivariate analysis reveals a hierarchy of survival determinants: the strongest mortality-associated factors are enriched for components of the mitotic cell cycle, while secondary clusters of genes are involved in extracellular matrix remodeling, cell motility, and angiogenesis. Survival-associated genomic features are indicative of immune infiltration into primary tumors and oxidative phosphorylation activity.
In vitro and in vivo analyses reveal that mortality-associated genes rarely promote the direct transformation of primary cells. Instead, CRISPR mutagenesis reveals that these genes largely represent tumor dependencies, and in their absence cancer cells fail to proliferate. Through this analysis, we have identified new genetic dependencies common across cancer cells, including C16ORF59 and C5ORF46. In total, our results represent the largest assessment of genomic features linked to cancer prognosis completed to date, and offer several lines of insight into the biological differences between fatal and benign cancers.
Note: This abstract was not presented at the meeting.
Citation Format: Joan Smith, Ann Lin, Chris Giuliano, Jason M. Sheltzer. Identification and characterization of survival-associated genomic features across tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 390. doi:10.1158/1538-7445.AM2017-390</jats:p
A tangled pathology: how AIDS became a "family disease" in Newark, New Jersey, 1970-1997
No full textAs AIDS proliferated in Newark, New Jersey through the 1980s, local AIDS-care advocates conceptualized AIDS in ways that reflected the disease’s impact on Newarkers. In reframing a problem that was predominately cast as a “gay disease” in North America, AIDS activists in Newark sought to highlight the growing prevalence of HIV and AIDS among urban communities of color. These efforts sought to direct national attention and resources towards affected “at risk” Newarkers by self-consciously portraying HIV and AIDS as a disease of the family. The lynchpin in this discourse was the pediatric AIDS patient. Discussions of HIV-positive children, and the “family disease” frame, became normalizing shorthand for addressing the complex biological transmission of the disease. By the late 1980s, advocates for Newark recognized the political utility in characterizing AIDS as a family disease at a time when the federal government was preparing to allocate funds for the areas hardest hit by the epidemic. This unique discourse was particularly useful in not only drawing attention to the problem of AIDS, but also to the societal “ills” associated with the disease’s prevalence among impoverished communities of color in Newark. As the family disease discourse evolved, Newark came to represent the ubiquitous, albeit insidious, urban problems that contributed to and exacerbated the epidemic in similar U.S. cities. Reserved almost exclusively to descriptions of families of color, the family disease discourse must be understood as—an implicit, if not explicit—response to mainstream perceptions of the inner city. Efforts to cope with AIDS in Newark benefited from the family disease script. Yet the legacy of the family disease discourse perhaps further encumbered cultural perceptions of inner city families as well. The family disease discourse thus inextricably linked the AIDS epidemic in impoverished communities color, and inner city families, to the pernicious social pathologies narrative that had over-determined perceptions of Newark since the late1960s.M.A.Includes bibliographical referencesIncludes vitaby Jason M. Chernesk
Mitotic entry in the presence of DNA damage is a widespread property of aneuploidy in yeast
No full textGenetic instability is a hallmark of aneuploidy in budding and fission yeast. All aneuploid yeast strains analyzed to date harbor elevated levels of Rad52-GFP foci, a sign of DNA damage. Here we investigate how continuously elevated levels of DNA damage affect aneuploid cells. We show that Rad52-GFP foci form during S phase, consistent with the observation that DNA replication initiation and elongation are impaired in some aneuploid yeast strains. We furthermore find that although DNA damage is low in aneuploid cells, it nevertheless has dramatic consequences. Many aneuploid yeast strains adapt to DNA damage and undergo mitosis despite the presence of unrepaired DNA leading to cell death. Wild-type cells exposed to low levels of DNA damage exhibit a similar phenotype, indicating that adaptation to low levels of unrepaired DNA is a general property of the cell's response to DNA damage. Our results indicate that by causing low levels of DNA damage, whole-chromosome aneuploidies lead to DNA breaks that persist into mitosis. Such breaks provide the substrate for translocations and deletions that are a hallmark of cancer
Transcriptional consequences of aneuploidy
No full textAneuploidy, or an aberrant karyotype, results in developmental disabilities and has been implicated in tumorigenesis. However, the causes of aneuploidy-induced phenotypes and the consequences of aneuploidy on cell physiology remain poorly understood. We have performed a metaanalysis on gene expression data from aneuploid cells in diverse organisms, including yeast, plants, mice, and humans. We found highly related gene expression patterns that are conserved between species: genes that were involved in the response to stress were consistently upregulated, and genes associated with the cell cycle and cell proliferation were downregulated in aneuploid cells. Within species, different aneuploidies induced similar changes in gene expression, independent of the specific chromosomal aberrations. Taken together, our results demonstrate that aneuploidies of different chromosomes and in different organisms impact similar cellular pathways and cause a stereotypical antiproliferative response that must be overcome before transformation.National Institutes of Health (U.S.) (GM056800)National Science Foundation (U.S.) (Predoctoral Fellowship
Interview: Jason Dittmer Interviewed by Steven M. Schnell, Editor, The Geographical Bulletin
No full textJason Dittmer is from Jacksonville, Florida, received his PhD from Florida State University in 2003, and has taught at University College London in the United Kingdom since 2007. He is the author of Popular Culture, Geopolitics, and Identity (Rowman and Littlefield, 2010) and the co-editor of Mapping the End Times: American Evangelical Geopolitics and Apocalyptic Visions (Ashgate, 2010). He is married to the lovely Stephanie and has two cats. They all live in southeast London
Gender disparities among independent fellows in biomedical research
No full textIndependent fellowships provide an opportunity for junior scientists to found their own lab directly after completing their PhD. However, these positions show a striking gender bias that has remained consistent for almost 30 years
Aneuploidy Drives Genomic Instability in Yeast
No full textAneuploidy decreases cellular fitness, yet it is also associated with cancer, a disease of enhanced proliferative capacity. To investigate one mechanism by which aneuploidy could contribute to tumorigenesis, we examined the effects of aneuploidy on genomic stability. We analyzed 13 budding yeast strains that carry extra copies of single chromosomes and found that all aneuploid strains exhibited one or more forms of genomic instability. Most strains displayed increased chromosome loss and mitotic recombination, as well as defective DNA damage repair. Aneuploid fission yeast strains also exhibited defects in mitotic recombination. Aneuploidy-induced genomic instability could facilitate the development of genetic alterations that drive malignant growth in cancer
Single-chromosome Gains Commonly Function as Tumor Suppressors
No full textSummary Aneuploidy is a hallmark of cancer, although its effects on tumorigenesis are unclear. Here, we investigated the relationship between aneuploidy and cancer development using cells engineered to harbor single extra chromosomes. We found that nearly all trisomic cell lines grew poorly in vitro and as xenografts, relative to genetically matched euploid cells. Moreover, the activation of several oncogenic pathways failed to alleviate the fitness defect induced by aneuploidy. However, following prolonged growth, trisomic cells acquired additional chromosomal alterations that were largely absent from their euploid counterparts and that correlated with improved fitness. Thus, while single-chromosome gains can suppress transformation, the genome-destabilizing effects of aneuploidy confer an evolutionary flexibility that may contribute to the aggressive growth of advanced malignancies with complex karyotypes
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