The Genetic and Developmental Basis of Human Birth Defect
The main focus of the team is to identify the genetic causes of human congenital malformation syndromes and elucidate the developmental processes disrupted in these conditions. Previous and current work indicates that this can uncover novel genetic mechanisms and offer insights into general mechanisms of development and even common disease. For instance, the deletion 22q11 causing DiGeorge syndrome is the largest known genetic risk factor for schizophrenia. Clinical and diagnosis and prognosis can be improved, and in some cases there is the prospect of new therapeutic intervention.
Of particular interest to the group are the 22q11.2 deletion syndrome (22q11DS) and CHARGE syndromes, and in researching these conditions our primary concern are the congenital heart and vascular defects seen when the main causative (haploinsufficient) genes - Tbx1 and Chd7 - are mutated. As these two genes encode transcriptional regulators identification of their targets is core to our work. This has led to further investigations of specific signalling pathways and processes e.g. the CXCL12/CXCR4/CXCR7 axis, SEMA3c and retinoic acid signalling.
The tools used include creation and analysis of models in mouse and zebrafish. We explore novel methods of imaging the phenotypes observed (in collaboration with UCL's CABI). Genetic approaches include high resolution, genome-wide, screens and sequencing (collaboration with UK10K project). We also collaborate across non-life science faculties via the CoMPLEX programme.