Investigation of the regulatory pathways that govern fidelity of cell division and tumorigenesis through aneuploidy

SCHEME: CORE

CALL: 2013

DOMAIN: BM - Translational Biomedical Research

FIRST NAME: Andreas

LAST NAME: Girod

INDUSTRY PARTNERSHIP / PPP: No

INDUSTRY / PPP PARTNER:

HOST INSTITUTION: University of Luxembourg

KEYWORDS: prognostic/ diagnostic biomarkers, HURP, CHD4, spindle assembly, aneuploidy, carcinogenesis, spindle assembly ckeckpoint

START: 2014-07-01

END: 2017-06-30

WEBSITE: https://www.uni.lu

Submitted Abstract

The proposed project is focused on cancer biology research, and more specifically on the identification and validation of novel prognostic/diagnostic markers. Faithful segregation of genetic material relies on correct chromosome congression during mitosis. The spindle assembly checkpoint maintains genome stability by delaying cell division until accurate chromosome segregation can be guaranteed. When the fidelity of this process is compromised however, abnormal numbers of chromosomes can be distributed to the daughter cells (aneuploidy), which is often associated with cancer. Miss-regulation of HURP (Hepatoma Up-Regulated Protein) leads to chromosome miss-segregation, ignoring the spindle checkpoint. HURP is also over-expressed in cancers, suggesting a role in tumorigenesis. In the present study the role of HURP and its newly identified partner, CHD4 (Chromodomain-helicase-DNA-binding protein 4), on correct chromosome alignment at the metaphase plate, as well as on causing aneuploidy will be examined. Moreover, the importance of the chromatin remodelling ATPase CHD4 in coordinating chromatin dynamics with cell division acting as an unusual, yet bona-fide Microtubule Associated Protein during mitosis will be examined. Further, validation of HURP and CHD4, as potential prognostic/diagnostic markers and risk factors for metastasis and chemoresistance will be performed.

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