A long standing interest of my research group has been the role of secreted signaling molecules in pattern formation and organogenesis. We have focused in particular on the Hedgehog (Hh) protein family, using genetic analysis in Drosophila to elucidate the pathway by which these proteins signal to the nucleus and using the zebrafish as a model in which to study their roles in vertebrate development.

One process that we have studied in some detail is the allocation of cells to distinct myogenic fates. We have found that Hh signaling plays a key role in specifying muscle fibre type and have identified the transcription factor Prdm1 as a critical target of Hh signaling in this cell fate decision. Using Chromatin immune precipitation combined with microarray analysis (ChIP on chip) we have identified multiple targets of Prdm1 in myoblasts.

A second area of investigation is the mechanisms by which Hh pathway components function. The unique properties of the zebrafish embryo make it very well suited to the in vivo analysis of signaling processes at the cellular and sub-cellular. We are particularly interested in the trafficking of the transmembrane proteins Patched and Smoothened and the nuclear cytoplasmic shuttling of the Gli transcription factors.

Another major interest of my group is the use of the zebrafish as a system in which to model human disease related processes. We have collaborated with clinician scientists in the establishment of models of Parkinson¿s disease, the inflammatory response and arteriogenesis and are exploring the use of these and other models as the basis for chemical genetic screens.

http://www.shef.ac.uk/bms/research/ingham