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Associate Professor

Ph.D. - University of Delaware

Phone: 301-405-3933
Email: ckeefer@umd.edu

Research Interests:

Understanding the Underlying Biological Mechanisms of Embryonic Development in Ruminants (cattle, goats)

What are the key-steps in determining trophectoderm (TE) vs. inner cell mass (ICM) lineage in mammalian embryos? Very little is known about the key triggers of TE determination in the early mouse embryos, less in the human and virtually nil in the ruminant. Our lab is studying the role of key transcription factors (Oct4, Nanog, CDX2) in TE and ICM determination in bovine and caprine embryos. Identification of regulatory mechanisms controlling trophoblast lineage differentiation will provide a better understanding of placental development and insights into the etiology of implantation failure and early pregnancy loss. Furthermore, an understanding of the regulatory mechanisms controlling ICM lineage and pluripotency can be directly applied to the development of self-renewing, pluripotent cell lines for use in the production of transgenic livestock.


• Refinement of Methods for Production of Genetically Modified Livestock.
  
  Somatic cell nuclear transfer (SCNT) provides an effective means of producing transgenic animals, particularly in cattle and goats. SCNT has many advantages over other methods of transgenic animal production:
  
  • It is more efficient in terms of animal usage,
  • It avoids the problem of mosaic animals that plagues transgenic animal production by pronuclear microinjection, and
  • It allows for a more thorough characterization of transgene incorporation (e.g., intactness of the gene, copy number, integration sites) prior to production of the animal.
  Despite these advantages, there is a critical need for a better source of donor cells. Fetal fibroblasts, the predominant donor cell type used in the production of transgenic livestock, tend toward senescence before transgene incorporation can be fully characterized. In our lab we are taking advantage of recent advances in the study of self-renewal in mouse embryonic stem cells in order to develop robust, self-renewing cell lines in cattle and goats.

 

Awards and Honors:
- President, International Embryo Transfer Society (IETS), 2003
- Vice president, International Embryo Transfer Society, 2002
- Board Of Governors, IETS, 1999 to 2004
- Editorial board, Cloning & Stem Cells
- EPA Scientific and Technological Achievement Award, 1990