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Nasser M. Rusan |
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Drosophila Central Brain Neuroblast |
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Postdoctoral Fellow (2005 - Present), Peifer Lab |
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Peifer Lab |
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Previous Life (Wadsworth Lab) |
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Last updated September 23rd, 2009 |
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In recent years, we have witnessed an exciting surge in centrosome biology research. This organelle has fascinated investigators for over a century, but we are just beginning to understand the complexity of its structure and regulation. Centrosomes consist of a pair of core centrioles surrounded by a cloud of pericentriolar material. Centrosome number is regulated and maintained by the centriole/centrosome duplication cycle that is tightly linked to the cell cycle, duplicating once, and only once in S-phase. Defects in centriole duplication can have detrimental effects on the cell and organism. If a cell receives too many |
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centrioles, this can lead to defects in mitotic spindle formation and, via multiple pathways, can lead to aneuploidy, which has been shown to promote tumor formation. If the cell receives too few, or no centrioles, then defects can arise in several ways, such as the loss of cilia and flagella, a leading cause of human ciliopathies. Loss of centrosomes can also lead to the transformation of stem cells (SCs). Paradoxically, some of the same properties that make normal SCs so powerful can be detrimental when adopted by mutant cells. Some tumors have been shown to originate from a small number of cancer SCs that divide uncontrollably to produce the majority of the tumor mass. Work from several labs, including my work in the Peifer lab, has revealed that defects in centrosome function in SCs can lead to cell overproliferation and, under certain conditions, tumor formation. This work has contributed to addressing the 100 year old question first asked by Boveri–do defects in centrosome number and function lead to malignant transformation? Recently, it was shown that in Drosophila SCs, the answer is YES. I believe that research into normal SC behavior and regulation will help us understand and combat ‘cancer stem cells.’ My work aims to answer questions in both the basic biogenesis of centrioles and centrosomes and their functions in SCs. Many issues remain poorly understood: how are centrioles constructed? How is centrosome-function properly regulated in SCs to assure the accuracy of the division axis, and thus the fidelity of asymmetric division? Do all SCs, in all tissues and organisms, undergo similar behavior and regulation? I will employ the powerful genetic tools available in Drosophila in synergy with modern super-resolution imaging of cultured and explanted Drosophila and mammalian tissues to address some of these questions.
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The Centriole Duplication Cycle |
