Our intention should not be to prove that our hypothesis is right, but to find out whether it is right. - Discorsi dei Due Massimi Sistemi, Galileo Galilei
Transcriptional Control of Morphogenesis in the Mouse Embryo
Our laboratory uses genetically-engineered and mutagenized mouse models to characterize normal and aberrant developmental processes in the embryo and to identify novel genes and regulatory networks that underlie congenital disease. With the knowledge obtained from our basic studies in developmental genetics and transcriptional regulation in the mouse embryo, we pursue analyses that explore how specific genetic mutations determine birth defects. By this approach, we attempt to rigorously model human congenital disease and to increase the knowledge of perturbed genetic and molecular mechanisms that cause abnormal morphogenesis and developmental aberrations.
We have a particular interest in understanding the roles that genes of the Pbx family execute in mammalian development. Pbx genes encode particular homeodomain-containing transcription factors that are critical for patterning and morphogenesis of the axial, craniofacial, and appendicular (limb) skeleton, as well as for the development of most internal organs. Our research focuses particularly on development of embryonic craniofacial and limb structures, since abnormal development of these organ systems results in congenital birth defects that do not only lower the quality of life, but are also socially stigmatizing. We also devote efforts to understand the development of the mammalian spleen using multiple genetically-engineered mouse models. While the spleen has vital roles in immune response and blood filtering its development remains poorly understood. Lack of spleen development, as in human Congenital Asplenia, causes lethal infections in neonates and young children.
Our ultimate goal and ambition are to make all basic knowledge derived from our studies in the mouse embryo available to those who will use it in diagnostic, interventional, and therapeutic settings.