Genomic Instability in Cancer
Many enzymes are required to replicate and repair DNA. These enzymes are generally highly specific, accurate machines that are precisely controlled in their interactions with and processing of DNA. Correct functioning allows a fine balance between accurate replication and repair of DNA on the one hand and genetic evolution on the other hand. Attenuation in specificity, accuracy or control results in genomic instability and can have disastrous results manifested as cancer and other genetic diseases.
My laboratory studies genomic instability. We are involved in molecular characterization of the changes that occur to the human genome to cause cancer. DNA microarray and next generation DNA resequencing technologies are being employed to characterize the changes in mRNA, microRNA, and DNA in cancer.
Molecular Mechanisms of Ataxia
Another effort of the lab is aimed at understanding how the repeat expansions cause disease. We are particularly interested in the subset of repeats located in introns and untranslated regions of their host genes. For example, the expanded repeats in myotonic dystrophy are transcribed to produce gain-of-function or “toxic” RNAs, which bind proteins to disturb splicing. One result is alterations in the ion channels necessary for nerve function. We are actively studying how other repeat expansions result in ataxia. Contrasting hypotheses are being tested: the first is that a gain-of-function RNA is responsible for the ataxia phenotypes, the second is that the expanded RNA interferes with its own translation resulting in a loss of expression of the host genes.
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