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Department of Diabetes and Metabolic Diseases Research
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Department of Medical Oncology and Therapeutics Research
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    ABSTRACT: A major challenge for the application of RNA- or DNA-oligonucleotides in biotechnology and molecular medicine is their susceptibility to abundant nucleases. One intriguing possibility to tackle this problem is the use of mirror-image (l-)oligonucleotides. For aptamers, this concept has successfully been applied to even develop therapeutic agents, so-called Spiegelmers. However, for technologies depending on RNA/RNA or RNA/DNA hybridization, like antisense or RNA interference, it has not been possible to use mirror-image oligonucleotides because Watson-Crick base pairing of complementary strands is (thought to be) stereospecific. Many scientists consider this a general principle if not a dogma. A recent publication proposing heterochiral Watson-Crick base pairing and sequence-specific hydrolysis of natural RNA by mirror-image ribozymes or DNAzymes (and vice versa) prompted us to systematically revisit the stereospecificity of oligonucleotides hybridization and catalytic activity. Using hyperchromicity measurements we demonstrate that hybridization only occurs among homochiral anti-parallel complementary oligonucleotide strands. As expected, achiral PNA hybridizes to RNA and DNA irrespective of their chirality. In functional assays we could not confirm an alleged heterochiral hydrolytic activity of ribozymes or DNAzymes. Our results confirm a strict stereospecificity of oligonucleotide hybridization and clearly argue against the possibility to use mirror-image oligonucleotides for gene silencing or antisense applications.
    PLoS ONE 02/2015; 10(2):e0115328. DOI:10.1371/journal.pone.0115328
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    ABSTRACT: The liver is a vital organ with critical functions in metabolism, protein synthesis, and immune defense. Most of the liver functions are not mature at birth and many changes happen during postnatal liver development. However, it is unclear what changes occur in liver after birth, at what developmental stages they occur, and how the developmental processes are regulated. Long non-coding RNAs (lncRNAs) are involved in organ development and cell differentiation. Here, we analyzed the transcriptome of lncRNAs in mouse liver from perinatal (day -2) to adult (day 60) by RNA-Sequencing, with an attempt to understand the role of lncRNAs in liver maturation. We found around 15,000 genes expressed, including about 2,000 lncRNAs. Most lncRNAs were expressed at a lower level than coding RNAs. Both coding RNAs and lncRNAs displayed three major ontogenic patterns: enriched at neonatal, adolescent, or adult stages. Neighboring coding and non-coding RNAs showed the trend to exhibit highly correlated ontogenic expression patterns. Gene ontology (GO) analysis revealed that some lncRNAs enriched at neonatal ages have their neighbor protein coding genes also enriched at neonatal ages and associated with cell proliferation, immune activation related processes, tissue organization pathways, and hematopoiesis; other lncRNAs enriched at adolescent ages have their neighbor protein coding genes associated with different metabolic processes. These data reveal significant functional transition during postnatal liver development and imply the potential importance of lncRNAs in liver maturation.
    PLoS ONE 12/2014; 9(12):e114917. DOI:10.1371/journal.pone.0114917
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    ABSTRACT: Melanoma continues to be one of the fastest growing cancers in terms of incidence. The workup of melanoma focuses on risk factors based on the visual aspects of a skin lesion. Risk factors including sun exposure increase the risk of melanoma. Staging is based on depth of invasion, mitotic rate, and spread into lymph nodes and other sites. Once diagnosed, wide excision is indicated for the primary lesion, and sentinel node biopsy for all but the thinnest of melanomas. Routine imaging workup for most thinner melanomas should be minimized, and is questionable in the asymptomatic patients even with thicker melanomas.
    Surgical Clinics of North America 10/2014; 94(5). DOI:10.1016/j.suc.2014.07.001


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Journal of the National Comprehensive Cancer Network: JNCCN 04/2014; 12(4):542-90.
Autophagy 04/2012; 8(4):1-100. DOI:10.4161/auto.19496

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