Projects
Some examples of the strategies being used by our laboratory investigators to understand the regulation and function of organ development and regeneration:
- Use of antisense morpholinos to selectively target individual or combinations of GATA factors, TBX factors, or components of the BMP signaling pathway during zebrafish embryogenesis, to gain insight into the "code" that regulates various aspects of hematopoiesis and cardiogenesis. This has also led us to surprising discoveries about the function of these pathways in other systems including liver, pancreas, gut, and sensory organs.
- Generation of novel transgenic zebrafish lines that allow us to conditionally inactivate Smads, GATA factors, or other regulatory components in a cell autonomous manner, in any cell type and at any developmental stage.
- Generation of novel lines of murine ES cells that also allow us to manipulate regulatory factors at various stages of in vitro development for studying the progenitor cell biology of hematopoietic, cardiogenic, and endoderm-derived cell lineages. This helps us define the target genes of these regulatory pathways, and discover new pathways that could be manipulated for cellular and regenerative therapies.
- The development of polysome profiling in the zebrafish system, coupled with state-of-the-art RNA sequencing protocols, allowing us to discover novel translationally regulated pathways and mechanisms.
- The development of new models in zebrafish for heart and liver regeneration to understand how these processes might be enhanced in mammals including humans.
- Chemical biology projects that use defined screens to find new small molecules that impact organ development and might be used as drug leads for research and therapy.
- New mouse and human ES and iPS cell models to study aging, neuro-endocrine tumors (carcinoids), asthma, stem cell niches, and other developmental programs.
In summary, we develop and exploit various animal and stem cell models, so that we can understand how cell types, tissues, and organs form, why this process can fail during embryogenesis and throughout life, and how regenerative processes might be reemployed to treat debilitating diseases.