Morphogeneic Signaling Network in Development and Disease
The global objective is to understand how embryos develop from a single cell to a complex organism, how genes control the development of organs and how abnormal regulation of these genes resulted in human diseases. We investigate the genetic control of cellular signaling and signal transduction mechanisms. By delineating these regulatory networks underlying normal developmental processes, we hope to advance the knowledge base of human diseases, leading to novel molecular therapies for the treatment of these diseases. To achieve our goals, we focus on (1) characterizing morphogenetic signaling pathways that regulate mammalian development, (2) elucidating the mechanism by which these developmental signals regulate cell growth, differentiation and survival, and (3) creating mouse models to study the molecular basis of human diseases
Member of the Wnt family proteins controls diverse developmental processes and several Wnt signaling molecules have been implicated in the development of different forms of cancer. We previously identified Axin as a negative regulator for the canonical Wnt pathway. Mutations of the Axin tumor suppressor have been linked to the development of human cancers, including hepatocellular carcinoma, medulloblastoma, colorectal and breast cancers. The Wnt-Axin signaling network is critical for mammalian development in health and disease.
Our current efforts concentrate on the importance of Wnt signaling and its interactions with other cellular signaling pathways during craniofacial morphogenesis, early embryonic and extraembryonic development, neural development, breast development and cancer. The interaction of Wnt with other cellular signaling pathways, such as FGF and BMP, appears to play an important role. We tackle these issues with a multidisciplinary approach, including genetics & genomics, stem cell & developmental biology, and protein chemistry & proteomics. We have developed several versatile tools for our oncoing and future studies.
To study cellular signaling that mediates cell fate determination, we have developed a novel system in mice for conditional gene expression at two levels: first by Cre-mediated recombination and then by rtTA-mediated Dox induction. This system not only allows inducible gene expression in a spatiotemporal specific and reversible fashion, but also is most ideal for lineage-specific activation.