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Lu B.,System Biosciences | Jiang Y.J.,University of California at San Francisco | Kim P.,University of California at San Francisco | Moser A.,University of California at San Francisco | And 3 more authors.
Journal of Lipid Research | Year: 2010

Phospholipids are required for epidermal lamellar body formation. Glycerol 3-phosphate acyltransferases (GPATs) catalyze the initial step in the biosynthesis of glycerolipids. Little is known about the expression and regulation of GPATs in epidermis/keratinocytes. Here, we demonstrate that GPAT 1, 3, and 4 are expressed in epidermis/ keratinocytes, whereas GPAT2 is not detected. In mouse epidermis, GPAT 3 and 4 are mainly localized to the upper layers whereas GPAT1 is found in both the upper and lower layers. GPAT1 and 3 mRNA increase during fetal rat epidermal development. No change in GPAT expression was observed in adult mice following acute permeability barrier disruption. Calcium-induced human keratinocyte differentiation increased GPAT3 mRNA whereas both GPAT1 and 4 mRNA levels decreased. In parallel, total GPAT activity increased 2-fold in differentiated keratinocytes attributable to an increase in N-ethylmaleimide (NEM) sensitive GPAT activity localized to microsomes with little change in NEM resistant activity, consistent with an increase in GPAT3. Furthermore, PPARγ or PPARδ activators increased GPAT3 mRNA, microsomal GPAT activity, and glycerol lipid synthesis without affecting the expression of GPAT1 or 4. Finally, both PPARγ and PPARδ activators increased GPAT3 mRNA via increasing its transcription. Thus, multiple isoforms of GPAT are expressed and differentially regulated in epidermis/keratinocytes.

Razvi E.S.,System Biosciences
Drugs of the Future | Year: 2013

Exosomes/microvesicles (EMVs) offer significant promise for the development of liquid biopsies for a number of disease classes, most notably cancer. The current challenges in the isolation and purification of EMVs are slowly being addressed by new technologies aimed at the research marketplace, as well as the downstream diagnostics market. Once isolated and purified, the challenge for the study of these vesicles moves towards interrogation of the cargo (e.g., RNA) and proteins contained therein. There is the need to "associate" specific molecular signatures with specific clinical sequelae. This is perhaps the most intractable problem and will require significant investment of resources and time to establish these relationships. Additionally, circulating tumor cells represent yet another class of circulating biomarkers, and it is believed that different types of circulating biomarkers will be deployed in liquid biopsies for different disease classes. Over the coming decade the marketplace will be segmented by disease classes first and technologies/ biomarker classes second. However, the inescapable conclusion is that the era of minimally invasive biopsies is coming closer, and will provide less painful procedures, better manage ment and cost-effective diagnostics. © 2013 Prous Science, S.A.U. or its licensors.

The Cambridge Healthtech Institutes (CHI) 18th International Molecular Medicine Tri-Conference 2011 brought together all the key stakeholders in the stem cells marketplace including academic researchers, researchers from biotechnology companies, as well as business leaders involved in various aspects of the regenerative medicine space. The focus of the stem cells track, of this 12-track conference, was on the translation of basic stem cell discoveries into preclinical and clinical milestones. Many presentations focused on the production of induced pluripotent stem cells from various patient populations and the potential utilization of induced pluripotent stem cells in the future for cellular therapy. In this article, I provide a snapshot of this conference and highlight selected presentations, giving the overall direction that the stem cell field is taking. © 2011 Future Medicine Ltd.

Juan D.,Boston University | Alexe G.,The Broad Institute of MIT and Harvard | Antes T.,System Biosciences | Liu H.,Rutgers University | And 8 more authors.
Urology | Year: 2010

Objectives: To identify a robust panel of microRNA signatures that can classify tumor from normal kidney using microRNA expression levels. Mounting evidence suggests that microRNAs are key players in essential cellular processes and that their expression pattern can serve as diagnostic biomarkers for cancerous tissues. Methods: We selected 28 clear-cell type human renal cell carcinoma (ccRCC), samples from patient-matched specimens to perform high-throughput, quantitative real-time polymerase chain reaction analysis of microRNA expression levels. The data were subjected to rigorous statistical analyses and hierarchical clustering to produce a discrete set of microRNAs that can robustly distinguish ccRCC from their patient-matched normal kidney tissue samples with high confidence. Results: Thirty-five microRNAs were found that can robustly distinguish ccRCC from their patient-matched normal kidney tissue samples with high confidence. Among this set of 35 signature microRNAs, 26 were found to be consistently downregulated and 9 consistently upregulated in ccRCC relative to normal kidney samples. Two microRNAs, namely, MiR-155 and miR-21, commonly found to be upregulated in other cancers, and miR-210, induced by hypoxia, were also identified as overexpressed in ccRCC in our study. MicroRNAs identified as downregulated in our study can be correlated to common chromosome deletions in ccRCC. Conclusions: Our analysis is a comprehensive, statistically relevant study that identifies the microRNAs dysregulated in ccRCC, which can serve as the basis of molecular markers for diagnosis. © 2010 Elsevier Inc. All rights reserved.

Van Dijk K.,Creighton University | Sarkar N.,System Biosciences
Methods in Molecular Biology | Year: 2011

Reverse genetic approaches have become invaluable tools to tap into the wealth of information provided by sequenced genomes. In 2007, sequencing of the Chlamydomonas reinhardtii genome was completed, and with this an increased demand for the development of reverse genetic strategies for gene analysis. In a variety of organisms, including Chlamydomonas, inverted repeat transgenes have been used to produce strains silenced for a specific gene due to the production of double stranded RNA (dsRNA). Here, we describe a tandem inverted repeat system designed to overcome some of the typical challenges that arise when transgenes are used to trigger gene silencing including the lack of a screenable phenotype, unpredictable levels of silencing, silencing of the transgene itself and thus loss of target gene silencing, and finally silencing of unintended genes (off-target genes). The described strategy allows selection of target gene silencing by inducing co-silencing of the target gene and a gene, MAA7, silencing of which produces a selectable RNAi-induced phenotype. This selection, therefore, precludes extensive molecular screening for transgenic strains exhibiting target gene silencing, and also ensures heritable silencing through many generations. © 2011 Springer Science+Business Media, LLC.

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