The role of Proline-Rich Homeodomain protein in tumourgenesis and other diseases of proliferation
The PRH/HHex transcription factor is an oligomeric protein that is required for multiple processes during early development including axis formation, haematopoiesis and development of the vasculature. PRH is also involved in the formation of almost all the major organs of the body. PRH is considered to be a tumour suppressor in blood cells of the myeloid lineage, but can function as an oncogene in lymphoid cells. Our recent work has also suggested that PRH plays a tumour suppressor role in breast and prostate tumour cells and that it can control the migration and invasion of tumour cells. PRH regulates the expression of many genes directly by binding to the promoter region or more indirectly by interacting with other transcription factors and growth control proteins.
Future projects available include the following areas of research
• understanding the role of PRH in haematopoietic and epithelial tumourgenesis.
• the role of PRH activity in vascular smooth muscle cell proliferative disorders that lead to cardiovascular diseases
• the role of PRH activity in trophoblast migration and invasion and its contribution to diseases such as pre-eclampsia
• understanding the mechanistic basis for PRH-dependent gene regulation in tumour stem cells
Techniques in the laboratory include techniques from the following disciplines, Molecular Biology, Cell Biology, Biophysics, Cancer Biology. Through collaboration the student will also learn 3D organotypic cultures, mouse models of tumourigenesis.
To apply, please submit your CV and a covering email/letter for consideration by the Supervisor.
Applications are invited from self-funding applicants only. Overseas applicants will need to meet the UoB English requirements which are IELTS of 7.0 overall with no less than 6.5 in any band or Pearson Academic test..
PRH/Hhex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin.
Kershaw R. et al.,Oncogene 2013 (pub. Nov 18th)
Dasatinib inhibits leukaemic cell survival by decreasing PRH/HHex phosphorylation resulting in increased repression of VEGF signalling genes
Noy P. et al., Leukaemia Research 2012 36(11):1434-7.
Protein kinase CK2 inactivates PRH/Hhex using multiple mechanisms to derepress VEGF signalling genes and promote cell survival
Noy P. et al.,Nucleic Acids Research 2012 40:9008-20
PRH/Hhex controls cell survival through coordinate transcriptional regulation of vascular endothelial growth factor signaling.
Noy P. et al., Mol. Cell Biol. 2010 30(9):2120-34
CK2 phosphorylation of the PRH/Hex homeodomain functions as a reversible switch for DNA binding.
Soufi A., et al.,Nucleic Acids Research (2009) 37 (10):3288-300