department of developmental biology

Associate Professor

Department of Developmental Biology
Develpmental Biology Program
Molecular Genetics Program
Molecular Cell Biology Program

Research Interests

Our research addresses two areas — cell fate specification during development and aging. Beautiful and intricate patterns of differentiated cells emerge during development. To investigate this process, we combine genetic analysis of C. elegans with biochemical analysis of homologous vertebrate proteins. Because developmental pathways have been extensively conserved, we can exploit the advantages of both systems. A conserved signal transduction pathway that includes a receptor tyrosine kinase, Ras, and mitogen-activated protein (MAP) kinase regulates multiple cell fate decisions during C. elegans development. Mutations that activate similar human pathways are a frequent cause of tumors. We used a genetic screen to identify 20 genes that are important for Ras-mediated signaling. These include Raf, MEK and MAP kinase, protein kinases involved in signaling in many species. We discovered a new signaling molecule, the protein kinase KSR, and showed it has a conserved function in vertebrates. We recently cloned several additional, novel signaling proteins. This signaling pathway regulates a transcription factor in the ETS family. Using mutation analysis, we found a conserved amino acid motif, FXFP, that allows MAP kinase to dock on this transcription factor. This is an interesting example of molecular recognition.

The progressive, deleterious changes that occur as animals age are of fundamental importance, yet poorly understood. C. elegans is well suited for investigating aging, since it has a short life span of ~18days. We have characterized several phenotypic changes that occur as worms age, and we are screening for mutations that affect the timing of these phenotypes. We hope to define regulatory circuits that control aging.

Kornfeld Biosketch

Education and Professional Experience:

• B.A., Yale University, Molecular Biophysics and Biochemistry, 1980 - 1984
• Ph.D., Department of Biochemistry, Stanford University School of Medicine, 1984 - 1991. Thesis advisor: David S. Hogness. Thesis topic: Function of the ultrabinhex homeotic gene during Drosophila development .
• M.D., Stanford University School of Medicine, 1984 - 1991
• Postdoctoral fellow, Department of Biology, M.I.T., 1991 - 1995. Postdoctoral advisor: H. Robert Horvitz. Research topic: Cell fate specification during C. elegans vulval development .
• Assistant Professor, Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 1995 - present
  

Honors and Awards:

• Medical Scientist Training Program Award, 1984 - 1991
• Damian Runyan-Walter Winchell Postdoctoral Fellowship, 1991 - 1994
• Leukemia Society of America Special Fellow Award, 1994 - 1997
• Edward Mallinckrodt, Jr. Foundation Award, 1996 - 1999
• Burroughs Wellcome Fund New Investigator Award in the Basic Pharmacological Sciences, 1998 - 2001

Selected Publications

Bruinsma JJ, Jirakulaporn T, Muslin AJ, Kornfeld K. Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling. Dev Cell 2002 2:567-578.

Fantz DA, Jacobs D, Glossip D, Kornfeld K. Docking sites on substrate proteins direct extracellular-signal regulated kinase (ERK) to phosphorylate specific residues. J Biol Chem 2001 276:27256-27265.

Jacobs D, Glossip D, Xing H, et al. Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase. Genes Dev 1999 13:163-175.

Jakubowski J, Kornfeld K. A local, high-density, single-nucleotide polymorphism map used to clone Caenorhabditis elegans cdf-1. Genetics 1999 153:743-752.

Kornfeld K, Hom DB, Horvitz HR. The KSR-1 gene encodes a novel protein kinase involved in Ras-mediated signaling in C. elegans. Cell 1995 83:903-913.

Contact Information

Kerry Kornfeld
Department of Developmental Biology
Washington University School of Medicine
Campus Box 8103
660 South Euclid Avenue
St. Louis, MO 63110
(314) 747-1480
kornfeld@wustl.edu

Laboratory Website

under construction

Developmental Biology Program Website

http://molecool.wustl.edu/DevBiol/