- Laboratory of Molecular Biology, NIDDK, NIH, 1993–Present
- Postdoctoral Fellow, Fred Hutchinson Cancer Research Center, 1986–1992
- Ph.D., University of Colorado, 1986
- B.A., University of Colorado, 1978
A goal of our research is to describe the formation of an organism after fertilization as a series of switches that regulate gene expression in each cell at the appropriate time and place during development. The relative simplicity of an organism like the worm C. elegans reduces the number of genes and cell types we need to integrate for this description while providing a rapid embryonic (1 day) and post-embryonic (3 days) developmental program. These attributes allow us to learn more about developmental processes in each individual cell in the organism, something that is extremely difficult in more complex animal systems.
We are interested in the transcriptional regulation of cell fate determination during metazoan development. Using the C. elegans system, we exploit forward and reverse genetic approaches to identify and characterize transcription factor function required for proper development of specific cell types, at single-cell resolution. Historically, our interest has primarily been directed at understanding muscle cell specification and differentiation as a model for both embryonic and postembryonic development. Our goal is to fully describe the transcriptional cascade that orchestrates the formation of this tissue from just after fertilization, throughout embryogenesis, and into adulthood.
Applying our Research
By understanding the nature and function of master regulatory genes, we can understand the logic behind developmental mechanisms used by all animals, including humans. More importantly, this knowledge allows us to both understand developmental diseases and to manipulate biology to provide therapeutic interventions or cures. For example, we can now generate stem cells from mature tissue samples by expressing a particular combination of master regulatory genes. This type of basic science research is the cornerstone of disease treatment and therapy.
Need for Further Study
Although we know in general terms the identity and function of several master regulatory genes, we lack a detailed understanding of how these factors orchestrate downstream events at the molecular level. A more detailed understanding is necessary to predict with confidence the full effects of turning on and off master regulators, an issue particularly important for harnessing the power of these genes to regulate developmental events and cure disease.
- O-linked-N-acetylglucosamine cycling and insulin signaling are required for the glucose stress response in Caenorhabditis elegans.
- Mondoux MA, Love DC, Ghosh SK, Fukushige T, Bond M, Weerasinghe GR, Hanover JA, Krause MW.
- Genetics (2011 Jun) 188:369-82. Abstract/Full Text
- A widespread distribution of genomic CeMyoD binding sites revealed and cross validated by ChIP-Chip and ChIP-Seq techniques.
- Lei H, Fukushige T, Niu W, Sarov M, Reinke V, Krause M.
- PLoS One (2010 Dec 29) 5:e15898. Abstract/Full Text
Research in Plain Language
In all animals, each cell in the body has the complete library of information it needs encoded within its DNA. This information is used by each cell to direct the formation of the entire organism. However, during the process of developing from a single fertilized cell to a whole animal, each cell uses only a small fraction of this information. How do cells “know” which parts of the library are needed to become muscle, nerve, or skin? Our research looks for the master regulators that “unlock” the necessary sections containing the information that each cell needs to develop properly. These master regulators turn on and off other genes that provide each cell type with the properties needed to carry out their cell-specific functions.