Alternative splicing is one of the major sources of the large transcriptional diversity found in ... more Alternative splicing is one of the major sources of the large transcriptional diversity found in human cells. Splicing variants have been shown to be associated with features like spreading and progression in several human tumors. Therefore, such variants may be of great importance as both diagnostic and therapeutic tools. Here, by using a set of criteria regarding the expression pattern of splicing variants and statistical analyses, we were able to screen the genome for exons overexpressed in tumors of specific tissues. However, as in other analyses attempting to identify tumor-associated variants, our list of candidates was seriously inflated with cases of genes differentially expressed in tumors. To exclude these cases and increase the probability of finding bona fide regulated splicing variants, we performed a serial analysis of gene expression (SAGE), excluding those genes that were shown to be upregulated in tumors. This allowed us to predict the overexpression of single exons in specific tumors. Our final group of candidates includes 1,386 exons belonging to 638 genes. Experimental validation of a few candidates in normal tissue, tumor cell lines, and patient samples suggests that most of these candidates are indeed tumor-associated exons. Further functional classification of our candidate genes shows that our final list is slightly inflated with cancer-related genes.
Retinal ganglion cell (RGC) loss after optic nerve damage is a hallmark of certain human ophthalm... more Retinal ganglion cell (RGC) loss after optic nerve damage is a hallmark of certain human ophthalmic diseases including ischemic optic neuropathy (ION) and glaucoma. In a rat model of optic nerve transection, in which 80% of RGCs are eliminated within 14 days, caspase-2 was found to be expressed and cleaved (activated) predominantly in RGC. Inhibition of caspase-2 expression by a chemically modified synthetic short interfering ribonucleic acid (siRNA) delivered by intravitreal administration significantly enhanced RGC survival over a period of at least 30 days. This exogenously delivered siRNA could be found in RGC and other types of retinal cells, persisted inside the retina for at least 1 month and mediated sequence-specific RNA interference without inducing an interferon response. Our results indicate that RGC apoptosis induced by optic nerve injury involves activation of caspase-2, and that synthetic siRNAs designed to inhibit expression of caspase-2 represent potential neuroprot...
Alternative splicing is one of the major sources of the large transcriptional diversity found in ... more Alternative splicing is one of the major sources of the large transcriptional diversity found in human cells. Splicing variants have been shown to be associated with features like spreading and progression in several human tumors. Therefore, such variants may be of great importance as both diagnostic and therapeutic tools. Here, by using a set of criteria regarding the expression pattern of splicing variants and statistical analyses, we were able to screen the genome for exons overexpressed in tumors of specific tissues. However, as in other analyses attempting to identify tumor-associated variants, our list of candidates was seriously inflated with cases of genes differentially expressed in tumors. To exclude these cases and increase the probability of finding bona fide regulated splicing variants, we performed a serial analysis of gene expression (SAGE), excluding those genes that were shown to be upregulated in tumors. This allowed us to predict the overexpression of single exons in specific tumors. Our final group of candidates includes 1,386 exons belonging to 638 genes. Experimental validation of a few candidates in normal tissue, tumor cell lines, and patient samples suggests that most of these candidates are indeed tumor-associated exons. Further functional classification of our candidate genes shows that our final list is slightly inflated with cancer-related genes.
Retinal ganglion cell (RGC) loss after optic nerve damage is a hallmark of certain human ophthalm... more Retinal ganglion cell (RGC) loss after optic nerve damage is a hallmark of certain human ophthalmic diseases including ischemic optic neuropathy (ION) and glaucoma. In a rat model of optic nerve transection, in which 80% of RGCs are eliminated within 14 days, caspase-2 was found to be expressed and cleaved (activated) predominantly in RGC. Inhibition of caspase-2 expression by a chemically modified synthetic short interfering ribonucleic acid (siRNA) delivered by intravitreal administration significantly enhanced RGC survival over a period of at least 30 days. This exogenously delivered siRNA could be found in RGC and other types of retinal cells, persisted inside the retina for at least 1 month and mediated sequence-specific RNA interference without inducing an interferon response. Our results indicate that RGC apoptosis induced by optic nerve injury involves activation of caspase-2, and that synthetic siRNAs designed to inhibit expression of caspase-2 represent potential neuroprot...
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Papers by N. Slager