Target
Discovery and Apoptosis Team
Team Leader:
Dr Spiros Linardopoulos
Chromosomal abnormalities
are a hallmark of human cancer, reflecting the deleterious consequences
of the gain or loss of genetic information. These abnormalities
may be a consequence of tumour progression, mis-segregated chromosomes
and aneuploidy. The fidelity of chromosome segregation is monitored
by mitotic checkpoints that delay entry into mitosis until a functional
centrosome is present. During this complex process, protein kinases
play important roles in promoting or retarding transitions between
different stages and checkpoints of the cell cycle. We aim to
further understand mitotic control and use this information to
identify and validate mitotic regulators as targets for cancer
therapy. Currently one of our targets is the STK15 (Aurora2)
gene, a mitotic kinase which has been found to be amplified in
more than 50% of primary colorectal cancers and 12% of primary
breast tumours as well as in breast, ovarian, colon, prostate,
neuroblastoma and cervical cell lines. Thus, STK15 represents
an attractive target for anticancer drug discovery. An additional
field for identification and validation of genes involved in cancer
is programmed cell death, also known as apoptosis. Apoptosis represents
the defence mechanism of the cell with accumulated oncogenic mutations.
Thus, defects in apoptotic signalling are thought to play an important
role in the development of different types of cancers. It is not
a surprise that the cell cycle and apoptosis are often deregulated
in tumours. Therefore, they represent an attractive field for
drug target discovery.
Details
of our current research
programme are available in the Projects Database.
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Structure
Target
Identification, Validation & Selection:
Development
of Preclinical Drug & Gene Therapy:
Clinical
Evaluation of New Treatments:
Last Modified
15/4/05
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