Michael W. Krause, Ph.D.

Senior Investigator

Developmental Biology Section, Laboratory of Molecular Biology

NIDDK

Scientific Director

NIDDK

Building 3, Room 2W05
3 Center Drive
Bethesda, MD 20814

301-402-4633

michaelkr@niddk.nih.gov

Research Topics

Research Goal

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.

Current Research

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.

Biography

  • 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

Selected Publications

  1. Mondoux MA, Love DC, Ghosh SK, Fukushige T, Bond M, Weerasinghe GR, Hanover JA, Krause MW. O-linked-N-acetylglucosamine cycling and insulin signaling are required for the glucose stress response in Caenorhabditis elegans. Genetics. 2011;188(2):369-82.

  2. Lei H, Fukushige T, Niu W, Sarov M, Reinke V, Krause M. A widespread distribution of genomic CeMyoD binding sites revealed and cross validated by ChIP-Chip and ChIP-Seq techniques. PLoS One. 2010;5(12):e15898.

  3. Love DC, Krause MW, Hanover JA. O-GlcNAc cycling: emerging roles in development and epigenetics. Semin Cell Dev Biol. 2010;21(6):646-54.

  4. Severance S, Rajagopal A, Rao AU, Cerqueira GC, Mitreva M, El-Sayed NM, Krause M, Hamza I. Genome-wide analysis reveals novel genes essential for heme homeostasis in Caenorhabditis elegans. PLoS Genet. 2010;6(7):e1001044.

  5. Love DC, Ghosh S, Mondoux MA, Fukushige T, Wang P, Wilson MA, Iser WB, Wolkow CA, Krause MW, Hanover JA. Dynamic O-GlcNAc cycling at promoters of Caenorhabditis elegans genes regulating longevity, stress, and immunity. Proc Natl Acad Sci U S A. 2010;107(16):7413-8.


This page was last updated on December 2nd, 2018