David Grunwald

Our goals are i) to uncover conserved mechanisms that regulate the generation and organization of tissues in the vertebrate embryo, and ii) to understand the roles of molecular and genetic pathways that are disturbed in inherited birth defects and syndromes. We work with zebrafish because of the detail with which tissue development can be monitored in the nearly transparent, rapidly developing zebrafish embryo, and the ease with which gene expression can be perturbed and mutants can be isolated. We identify genes of interest either because of their mutant phenotypes affecting zebrafish embryo development or because of their roles in human disease processes. We then use the zebrafish to uncover the molecular and cellular processes that are normally governed by the genes and perturbed by mutations. To advance our goals we have developed methods to precisely edit the zebrafish genome, allowing us, for example, to recreate human mutations in the zebrafish or to express fluorescent proteins or enzymes from any endogenous locus. The genome editing tools also allow us to remove genes in a tissue-specific manner to study their roles in specific developmental contexts.

Ongoing research projects include study of: 1) transcription patterns that maintain the pluripotent stem cell state, 2) the role of calcium mobilization in intercellular Hedgehog Growth Factor signaling and left/right patterning, 3) the genetic basis of osteoarthritis, and 4) methods for advancing genome editing in zebrafish.