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H. Joseph Yost

Professor of Neurobiology and Anatomy

B.S. Creighton University

Ph.D. University of Chicago

Research

References

jyost@genetics.utah.edu

Joe Yost's PubMed Literature Search

Research

All animals start life as a single cell, the fertilized egg, which divides into hundreds of different cell types. Our long-term research goal is to understand the genes, molecules and developmental mechanisms that regulate the assignment of different cell identities in functionally appropriate positions in the developing vertebrate embryo. This top-down approach utilizes embryonic phenotypes to uncover novel genetic pathways and cellular mechanisms ranging from extracellular signaling to genome-wide regulation of transcriptional networks.

Left-Right Axis Formation, Cilia and Cardiac Development. Our lab is a founder and leader in the field of vertebrate left-right development. Our research utilizes zebrafish, Xenopus and mice to discover the genes, molecular and cellular mechanisms that control asymmetric development of the brain, heart and gut. We have discovered novel mechanisms by which major cell-cell signaling pathways (FGF, TGFbeta and Wnt) control cell migration, cilia function and downstream pathways. In addition, we are using genome-wide approaches to elucidate the regulatory networks that control heart development in zebrafish, with the goal of understanding human complex congenital cardiac defects that are the leading cause of death in the first year.

GAG Sulfation Code. Heparan Sulfate Proteoglycans (HSPGs) are cell surface proteins with long chains of repeating sugar units (glycosaminoglycans; GAGs). Our discovery that a family of HSPGs control cell signaling pathways, cell migration and fibrillogenesis led to our focus on gene families that regulate proteoglycan biochemistry and function. Our results suggest the existence of a “GAG sulfation code” in which specific sulfation patterns on cell surface GAGs control specific cell-cell signaling decisions. The GAG sulfation code could provide enormous molecular diversity that dwarfs the informational content of the genome. Discovering out how this GAG sulfation code is regulated and how it is utilized in biology will be one of the major challenges in the “postgenomic era” and will provide important therapeutic targets for a wide range of human diseases.

Cancer Genetics. In humans, Li-Fraumeni syndrome (LFS) is a familial cancer predisposition syndrome in which tumors display loss of heterozygosity (LOH). Using our zebrafish developmental genetics perspective, we designed genetic screens in zebrafish embryos to identify mutations in LFS genes that give tumors in adult zebrafish, to identify novel genes in the p53-regulatory pathway, and to provide the first model with which to study the molecular mechanisms of LOH in zebrafish. Strikingly, these novel p53-pathway genes are highly conserved and misregulated in human cancers. Our long-term goals are to discover new genes in cancer biology that will serve as biomarkers for cancer progression in humans and to use drug screens in zebrafish to discover compounds that ameliorate the effects of specific tumorigenic mutations.

References