Prostate Development and Cancer
The prevalence of prostate cancer has highlighted the importance of understanding how the prostate develops and functions and what steps are required for tumour formation and progression. Many features of prostate organogenesis are paralleled in tumour formation and developmental pathways have been shown to be active in prostate cancer. Therefore understanding the development of the normal prostate will provide insight into neoplastic transformation and may help in the identification of novel predictive biomarkers and the development of drug therapies and combinations to treat prostate cancer. Using genetic in vivo models and in vitro cell and organ culture techniques we are studying the role of genes such as SOX9 in prostate development and cancer. We are also analysing the functional role of the cancer related genes such as β-catenin and the tumour suppressors PTEN and BRCA2 in prostate biology.
External Funding: NCRI, CRUK
Gonad and Adrenal Development
The focus of our work is to study the differentiation of steroidogenic cells of the gonad and adrenal. We are interested in analysing the molecular and cellular interaction events that determine the development of testicular Leydig cells and adrenal cortical cells and what regulates the production of the specific steroids during embryogenesis. Using in vivo genetic models we have been investigating the transcriptional control of steroidogenic cell development including the role of the transcriptional cofactor CITED2 and its interacting partner Wilms’ Tumour (WT-1) in the regulation of the expression of the hormone receptor SF-1.
Our emphasis is on the biological roles of these factors on the development of the gonad and adrenal. We have developed steroid specific Cre expressing in vivo models that allow us to genetically modify genes in a tissue specific manner. Using these tools we are investigating the role of different genes in the steroid producing cells of the testis, ovary and adrenal. Other experimental approaches include the use of in vitro organ cultures to analyse cellular interactions and effects of compounds that affect known molecular pathways.
External Funding: MRC, BBSRC