Cell division has been a focus of study for more than a century. During this process, the genetic information is replicated and divided to ensure genetic fidelity in the subsequent generation. Additional structures, like centrosomes, are replicated as well, to ensure that the daughter cell has all of the necessary components to function. However, a step of cell division that has long been overlooked is that of the fate of the midbody (MB) after abscission. The MB is an organelle formed in the intracellular bridge between the nascent daughter cells while the cleavage furrow constricts during cytokinesis. To complete abscission, the intracellular bridge between the two cells is severed and one daughter cell remains attached to the post abscission MB (MB derivative). What is interesting is that the number of MB derivatives in a cell appears to differ in different cell types. Furthermore, the cells that retain MB derivatives continue to do so in following rounds of division, accumulating several MB derivatives in one cell. Preliminary evidence showing a high number of MB derivatives in stem cells (versus differentiated cells), suggests that accumulation and retention of this structure is related to the progenitor state of the cell. Moreover, cancer cells also appear to contain high numbers of MB derivatives. Because cell division is such a fundamental process, affecting aging, reproduction, and several diseases, it is of intrinsic scientific interest to understand the molecular decisions made at each stage. How does the fate of the MB derivative differ in different cell types? What is directing MB accumulation? What role do these structures play in maintaining cancer cell populations? This project focuses on a series of experiments designed to address fundamental questions about the significance and clinical implications of MB derivative accumulation. These questions will be investigated in cultured and human cells via a series of molecular, biochemical, time lapse and fixed cell imaging methods. The relationship between MB derivative accumulation and tumorigenesis will be studied in vivo using mouse models as well as in vitro. Overall, this project serves to understand the mechanisms behind the accumulation of the MB derivative, an asymmetrically accrued product of cell division. It focuses on the contributions the accumulation of this organelle makes to the progenitor qualities of a cell and cancer cell proliferation. As a result, there is potential for the discovery of new stem cell markers, for a better understanding of what makes a cell a stem cell, and to reveal new routes for targeted cancer therapy

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F05-J (20))
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Hagan, Ann A
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University of Massachusetts Medical School Worcester
Anatomy/Cell Biology
Schools of Medicine
United States
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Kuo, Tse-Chun; Chen, Chun-Ting; Baron, Desiree et al. (2011) Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity. Nat Cell Biol 13:1214-23