Enhancer malfunction in cancer

Published on April 2, 2014   41 min

Other Talks in the Series: Epigenetics, Chromatin, Transcription and Cancer

0:00
Hello. My name is Ali Shalati. I'm going to share with you the recent stories from the laboratory and the function of enhancer in regulation of promoter activity, and how malfunction enhancer properties resulting pathogenesis of human cancer.
0:16
For over 20 years now, the burning question in my laboratory has been why chromosomal translocation involving the MLL gene results in pathogenesis of hematological malignancies. MLL gene which encoded by about 4,000 amino acid containing protein undergoes frequent translocation with large number of translocation partners as shown here on the right hand side. And translocation of MLL to many of these translocation partners result in pathogenesis of hematological malignancies. As shown in the bottom here, there are several examples of MLL translocation, an 11-4 translocation on the left hand side of the screen and a couple of 11-19 translocations on the right hand side of the screens. And most of these translocations are detected in children upon cytogenetics. And analysis of blood from the kids shows that there's a high level of white blood cell exist in these patients.
1:11
Normally, we have about 1% of white blood cells in our system. Looking at blood analysis from leukemic patients, some of these patients have over 80% of white blood cells in their system, which complications of infiltration of these white blood cells in many tissues and organs result death for these children.
1:30
MLL translocations mostly afflicts young adults, early adolescents and infants. And very little is known about why these translocation causes pathogenesis of hematological malignancies. So a true understanding of molecular properties of MLL translocational leukemia is going to be very important for development of targeted therapeutics.
1:52
My laboratory for over 20 years now has been taking advantage of genetic and biochemistry multiple model system including Saccharomyces cerevisiae, Drosophila melanogaster, mouse, and also tissue sample and human cell lines that we have been working in the laboratory in the hope of understanding why translocations of MLL results in leukemic pathogenesis. There will be a little emblem on the bottom that tells you what model system I'm talking about in a given slide, and our work rapidly moves between model system trying to define the role of the factors that Ive been studying in leukemic pathogenesis.
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Enhancer malfunction in cancer

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