Cancer Proteomics Group
Head of laboratory:
Following the pioneering research of Kinzler and Vogelstein (Science 314 (2006) 268-274), it is clear that cancers such as colorectal and breast cancers contain on average more than 90 mutations. While some of these mutations may represent "collateral damage" following the loss of p53 function, it is clear that the mutations and consequent proteomic changes that drive cancers are more complex than we thought (or hoped). It is well known that the levels of a particular mRNA found in a cancer do not necessarily correlate with the levels of the corresponding protein. It is now known that expression of mRNAs may be modulated by miRNAs, a rapidly developing area. Proteins carry out most of the functions of a cell; the properties of a cell (phenotype) are largely determined by proteins that may combine in large dynamic complexes. Human cells contain approximately 22,000 genes that encode more than 100,000 primary protein translation products when mRNA splice variants are included. Then we must consider the permutations and combinations of different post-translational modifications, exemplified by phosphorylations. It is clear that we are dealing with a collective human proteome of more than 1,000,000 different protein species.
There are approximately 220 different human cell types that are controlled by different genetic programs resulting in the expression of different subsets of proteins and therefore different cellular phenotypes. The multiple (~90) mutations in cancers result in changes in the proteome of the cells when compared with normal cells. The Cancer Proteomics Group uses techniques such as two-dimensional fluorescence difference gel electrophoresis (DIGE), isobaric tag for relative and absolute quantitation (iTRAQ), and mass spectroscopy to identify proteins that are differentially abundant in cancer relative to normal cells, or in drug-treated cancers relative to untreated cells. Such high throughput analyses enable elucidation of mechanisms of cancer transformation, drug mechanisms and resistance. The use of antibody microarrays to capture live cells from suspensions - see (Medsaic) - enables surface profiling of cancers such as leukaemias, colorectal cancer and melanoma. Profiles or patterns of surface molecules (CD antigens) on cancers enable their classification, and may also provide targets for therapeutic antibodies, the most rapidly growing area of pharmaceuticals.
