CRISPR-Mediated VHL Knockout Generates an Improved Model for Metastatic Renal Cell Carcinoma.

Metastatic renal cell carcinoma (mRCC) is nearly incurable and accounts for most of the mortality associated with RCC. Von Hippel Lindau (VHL) is a tumour suppressor that is lost in the majority of clear cell RCC (ccRCC) cases. Its role in regulating hypoxia-inducible factors-1α (HIF-1α) and -2α (HIF-2α) is well-studied. Recent work has demonstrated that VHL knock down induces an epithelial-mesenchymal transition (EMT) phenotype. In this study we showed that a CRISPR/Cas9-mediated knock out of VHL in the RENCA model leads to morphologic and molecular changes indicative of EMT, which in turn drives increased metastasis to the lungs. RENCA cells deficient in HIF-1α failed to undergo EMT changes upon VHL knockout. RNA-seq revealed several HIF-1α-regulated genes that are upregulated in our VHL knockout cells and whose overexpression signifies an aggressive form of ccRCC in the cancer genome atlas (TCGA) database. Independent validation in a new clinical dataset confirms the upregulation of these genes in ccRCC samples compared to adjacent normal tissue. Our findings indicate that loss of VHL could be driving tumour cell dissemination through stabilization of HIF-1α in RCC. A better understanding of the mechanisms involved in this phenomenon can guide the search for more effective treatments to combat mRCC

The emergence and diffusion of DNA microarray technology

The network model of innovation widely adopted among researchers in the economics of science and technology posits relatively porous boundaries between firms and academic research programs and a bi-directional flow of inventions, personnel, and tacit knowledge between sites of university and industry innovation. Moreover, the model suggests that these bi-directional flows should be considered as mutual stimulation of research and invention in both industry and academe, operating as a positive feedback loop. One side of this bi-directional flow – namely; the flow of inventions into industry through the licensing of university-based technologies – has been well studied; but the reverse phenomenon of the stimulation of university research through the absorption of new directions emanating from industry has yet to be investigated in much detail. We discuss the role of federal funding of academic research in the microarray field, and the multiple pathways through which federally supported development of commercial microarray technologies have transformed core academic research fields. Our study confirms the picture put forward by several scholars that the open character of networked economies is what makes them truly innovative. In an open system innovations emerge from the network. The emergence and diffusion of microarray technologies we have traced here provides an excellent example of an open system of innovation in action. Whether they originated in a startup company environment that operated like a think-tank, such as Affymax, the research labs of a large firm, such as Agilent, or within a research university, the inventors we have followed drew heavily on knowledge resources from all parts of the network in bringing microarray platforms to light. Federal funding for high-tech startups and new industrial development was important at several phases in the early history of microarrays, and federal funding of academic researchers using microarrays was fundamental to transforming the research agendas of several fields within academe. The typical story told about the role of federal funding emphasizes the spillovers from federally funded academic research to industry. Our study shows that the knowledge spillovers worked both ways, with federal funding of non-university research providing the impetus for reshaping the research agendas of several academic fields

Foundational studies for measuring the impact, prevalence, and patterns of publicly sharing biomedical research data

Many initiatives encourage research investigators to share their raw research datasets in hopes of increasing research efficiency and quality. Despite these investments of time and money, we do not have a firm grasp on the prevalence or patterns of data sharing and reuse. Previous survey methods for understanding data sharing patterns provide insight into investigator attitudes, but do not facilitate direct measurement of data sharing behaviour or its correlates. In this study, we evaluate and use bibliometric methods to understand the impact, prevalence, and patterns with which investigators publicly share their raw gene expression microarray datasets after study publication.To begin, we analyzed the citation history of 85 clinical trials published between 1999 and 2003. Almost half of the trials had shared their microarray data publicly on the internet. Publicly available data was significantly (p=0.006) associated with a 69% increase in citations, independently of journal impact factor, date of publication, and author country of origin.Digging deeper into data sharing patterns required methods for automatically identifying data creation and data sharing. We derived a full-text query to identify studies that generated gene expression microarray data. Issuing the query in PubMed Central, Highwire Press, and Google Scholar found 56% of the data-creation studies in our gold standard, with 90% precision. Next, we established that searching ArrayExpress and the Gene Expression Omnibus databases for PubMed article identifiers retrieved 77% of associated publicly-accessible datasets.We used these methods to identify 11603 publications that created gene expression microarray data. Authors of at least 25% of these publications deposited their data in the predominant public databases. We collected a wide set of variables about these studies and derived 15 factors that describe their authorship, funding, institution, publication, and domain environments. In second-order analysis, authors with a history of sharing and reusing shared gene expression microarray data were most likely to share their data, and those studying human subjects and cancer were least likely to share.We hope these methods and results will contribute to a deeper understanding of data sharing behavior and eventually more effective data sharing initiatives

Biomedical informatics and translational medicine

Biomedical informatics involves a core set of methodologies that can provide a foundation for crossing the "translational barriers" associated with translational medicine. To this end, the fundamental aspects of biomedical informatics (e.g., bioinformatics, imaging informatics, clinical informatics, and public health informatics) may be essential in helping improve the ability to bring basic research findings to the bedside, evaluate the efficacy of interventions across communities, and enable the assessment of the eventual impact of translational medicine innovations on health policies. Here, a brief description is provided for a selection of key biomedical informatics topics (Decision Support, Natural Language Processing, Standards, Information Retrieval, and Electronic Health Records) and their relevance to translational medicine. Based on contributions and advancements in each of these topic areas, the article proposes that biomedical informatics practitioners ("biomedical informaticians") can be essential members of translational medicine teams

Contract and Grant Awards Fiscal Year 2000

Message from the Vice Provost for Research I invite you to read this report Contract and Grant Awards FY00, which lists contract and grant (C&G) awards received by the University of New Mexico (UNM) during the period from July 1, 1999 - June 30, 2000. These awards represent new funds that were acquired during FY00 by the main campus, branch campuses and education centers and the Health Sciences Center (HSC). The HSC includes the School of Medicine, College of Nursing and College of Pharmacy. The awards received for FY00 total $217.4M, of which$139.9M is attributed to the main campus. These awards assist in providing resources that are necessary to enhance the quality of research and teaching at UNM, as well as the opportunities for students to be trained in state-of-the-art laboratories in a multitude of disciplines. Please join me in thanking our dedicated faculty, staff and students involved in the sponsored research, public service and instruction efforts at UNM. It is their successful endeavors that enhance UNM\u27s visibility at the national and international levels, as well as contribute to the economic growth of New Mexico and the region. Thanks are also due to a number of individuals who have helped in preparing this report. In particular, I would like to acknowledge the efforts of Denise Wallen, Ann Powell and Valerie Roybal of the Office of Research Services, and Marcia Sletten and Lee Gulbransen of the Health Sciences Center. I welcome your comments and questions with respect to this report, and other issues related to research activities at the University of New Mexico. John K. McIver Interim Vice Provost for Researc

Annual St. Cloud State University Student Research Colloquium 2006

2006 Student Research Colloquium Proceedings include Acknowledgements, Program highlights, Schedule of events, Program, Student awards ceremony, Abstracts, Student presenter index, Project sponsor index, Map of Atwood Memorial Center