Scheme: Wolfson Research Merit Awards
Organisation: University of Leicester
Dates: Jan 2010-Dec 2014
Summary: More than one-third of humans worldwide will be affected by cancer at some point in their lives and cancer is the second biggest killer of humans after heart disease. Cancer is essentially a disease of cell division and usually results from damage to one or more of the genes involved in controlling cell division. In recent research it has been identified that a key gene controlling cell division, called BRAF, is damaged or mutated in a high proportion of human cancers. My research is centred on BRAF, with specific emphasis on investigating the molecular mechanisms by which mutation of this gene drives cancer initiation and progression.
A conundrum has recently arisen with BRAF in that BRAF mutations have also been detected in a group of rare developmental disorders, collectively called “RASopathies”, that are characterised by reduced postnatal growth, facial disfigurement, mental retardation, heart defects and skin anomalies. One of the BRAF mutations shared in common by RASopathy patients and cancer patients is L597VBRAF in which a leucine (L) amino acid at position 597 of the protein is converted to valine (V). The research described in this project aims to address why L597VBRAF can contribute to cancer in some situations but to developmental disorders in others. Since it is not easy to gain access to human tissue samples, we are using the mouse as a model organism because we can recapitulate both diseases in this species.
Most current evidence suggests that whether cancer develops or not is dependent on the expression of negative feedback regulators that modulate L597VBRAF output. In collaboration with researchers in the USA, we are undertaking screens to find messenger RNAs and proteins whose expression is up or down regulated in L597VBRAF expressing mouse tissues. It is believed that these screens will lead to the identification of modulators of BRAF that may be used to combat BRAF-driven cancer as well as to treat RASopathy patients.
Scheme: University Research Fellowship
Dates: Jan 1995-Sep 2003
Summary: This project summary is not available for publication.