Publications by authors named "Arthur Donny Strosberg"

4 Publications

  • Page 1 of 1

Comprehensive molecular characterization of human adipocytes reveals a transient brown phenotype.

J Transl Med 2015 Apr 30;13:135. Epub 2015 Apr 30.

Laboratory of Genetic Medicine & Immunology, Weill Cornell Medical College in Qatar, P.O. Box 24144, Doha, Qatar.

Background: Functional brown adipose tissue (BAT), involved in energy expenditure, has recently been detected in substantial amounts in adults. Formerly overlooked BAT has now become an attractive anti-obesity target.

Methods And Results: Molecular characterization of human brown and white adipocytes, using a myriad of techniques including high-throughput RNA sequencing and functional assays, showed that PAZ6 and SW872 cells exhibit classical molecular and phenotypic markers of brown and white adipocytes, respectively. However, the pre-adipocyte cell line SGBS presents a versatile phenotype. A transit expression of classical brown markers such as UCP1 and PPARĪ³ peaked and declined at day 28 post-differentiation initiation. Conversely, white adipocyte markers, including Tcf21, showed reciprocal behavior. Interestingly, leptin levels peaked at day 28 whereas the highest adiponectin mRNA levels were detected at day 14 of differentiation. Phenotypic analysis of the abundance and shape of lipid droplets were consistent with the molecular patterns. Accordingly, the oxidative capacity of SGBS adipocytes peaked on differentiation day 14 and declined progressively towards differentiation day 28.

Conclusions: Our studies have unveiled a new phenotype of human adipocytes, providing a tool to identify molecular gene expression patterns and pathways involved in the conversion between white and brown adipocytes.
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http://dx.doi.org/10.1186/s12967-015-0480-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438513PMC
April 2015

PAZ6 cells constitute a representative model for human brown pre-adipocytes.

Front Endocrinol (Lausanne) 2012 2;3:13. Epub 2012 Feb 2.

Department of Infectology, The Scripps Research Institute-Florida Jupiter, FL, USA.

The role of brown adipose tissue (BAT) in human metabolism and its potential as an anti-obesity target organ have recently received much renewed attention. Following radiological detection of substantial amounts of BAT in adults by several independent research groups, an increasing number of studies are now dedicated to uncover BAT's genetic, developmental, and environmental determinants. In contrast to murine BAT, human BAT is not present as a single major fat depot in a well-defined location. The distribution of BAT in several areas in the body significantly limits its availability to research. A human brown adipocyte cell line is therefore critical in broadening the options available to researchers in the field. The human BAT-cell line PAZ6 was created to address such a need and has been well characterized by several research groups around the world. In the present review, we discuss their findings and propose potential applications of the PAZ6 cells in addressing the relevant questions in the BAT field, namely for future use in therapeutic applications.
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http://dx.doi.org/10.3389/fendo.2012.00013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355992PMC
July 2012

Core as a novel viral target for hepatitis C drugs.

Viruses 2010 Aug 20;2(8):1734-51. Epub 2010 Aug 20.

Department of Infectology, The Scripps Research Institute-Scripps Florida, 130 Scripps Way, Jupiter, FL-33458, USA; E-Mails: (S.K.); (V.T.); (G.M.).

Hepatitis C virus (HCV) infects over 130 million people worldwide and is a major cause of liver disease. No vaccine is available. Novel specific drugs for HCV are urgently required, since the standard-of-care treatment of pegylated interferon combined with ribavirin is poorly tolerated and cures less than half of the treated patients. Promising, effective direct-acting drugs currently in the clinic have been described for three of the ten potential HCV target proteins: NS3/NS4A protease, NS5B polymerase and NS5A, a regulatory phosphoprotein. We here present core, the viral capsid protein, as another attractive, non-enzymatic target, against which a new class of anti-HCV drugs can be raised. Core plays a major role in the virion's formation, and interacts with several cellular proteins, some of which are involved in host defense mechanisms against the virus. This most conserved of all HCV proteins requires oligomerization to function as the organizer of viral particle assembly. Using core dimerization as the basis of transfer-of-energy screening assays, peptides and small molecules were identified which not only inhibit core-core interaction, but also block viral production in cell culture. Initial chemical optimization resulted in compounds active in single digit micromolar concentrations. Core inhibitors could be used in combination with other HCV drugs in order to provide novel treatments of Hepatitis C.
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http://dx.doi.org/10.3390/v2081734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185734PMC
August 2010

A time-resolved fluorescence-resonance energy transfer assay for identifying inhibitors of hepatitis C virus core dimerization.

Assay Drug Dev Technol 2010 Feb;8(1):96-105

Department of Infectology, The Scripps Research Institute-Scripps Florida, Jupiter, Florida 33458, USA.

Binding of hepatitis C virus (HCV) RNA to core, the capsid protein, results in the formation of the nucleocapsid, the first step in the assembly of the viral particle. A novel assay was developed to discover small molecule inhibitors of core dimerization. This assay is based on time-resolved fluorescence resonance energy transfer (TR-FRET) between anti-tag antibodies labeled with either europium cryptate (Eu) or allophycocyanin (XL-665). The N-terminal 106-residue portion of core protein (core106) was tagged with either glutathione-S-transferase (GST) or a Flag peptide. Tag-free core106 was selected as the reference inhibitor. The assay was used to screen the library of pharmacologically active compounds (LOPAC) consisting of 1,280 compounds and a 2,240-compound library from the Center for Chemical Methodology and Library Development at Boston University (CMLD-BU). Ten of the 28 hits from the primary TR-FRET run were confirmed in a secondary amplified luminescent proximity homogeneous assay (ALPHA screen). One hit was further characterized by dose-response analysis yielding an IC(50) of 9.3 microM. This 513 Da compound was shown to inhibit HCV production in cultured hepatoma cells.
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http://dx.doi.org/10.1089/adt.2009.0217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2971647PMC
February 2010