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overview
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Alternative splicing (AS) is a highly specialized RNA processing mechanism in higher eukaryotes and a key control point in gene expression regulation. AS enables cells to produce multiple mRNAs and multiple proteins from a single gene, which can facilitate to perform specialized functions. Errors in splicing contribute to many aspects of human diseases, including cancer. AS is regulated by cis-elements in the RNA and trans-acting splicing factors comprised of RNA-binding proteins. Cancer cells often display alterations in splicing, many of which contribute to disease. Some of these alterations are caused by mutations in splicing-regulatory cis-elements, whereas others result from defects in splicing factors, such as abnormal expression, mutation, or post-translational modification. AS often gives rise to transcripts comprising a premature termination codon (PTC). Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism, which selectively degrades mRNAs with PTC. Tumor cells often exploit AS or/and NMD for survival benefit by altering the expression or function of tumor-suppressors, oncogenes, tumor-specific neo-antigens, important proteins in signaling pathways, or RNA-binding proteins. I am interested to study the mechanisms of AS and NMD misregulation in cancer, and the means by which faulty AS or/and NMD can be corrected for therapy. My lab utilizes biochemistry, molecular biology, genome editing, transcriptomics, proteomics, computational biology, and antisense pharmacology to study RNA metabolism in normal and cancer cells to contribute in developing effective cancer therapies.
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