Our research addresses two areas—organismal aging and the biology of metals during growth and development. Our studies of metals focus on zinc, which is essential for all life. To investigate zinc biology, we combine genetic analysis of C. elegans with biochemical analysis of purified proteins. Because zinc homeostasis pathways have been extensively conserved, we can translate discoveries made in worms into mammalian systems. We have identified a family of zinc transport proteins (CDF) that mediate high zinc homeostasis by sequestering zinc in lysosomes or excreting zinc out of the animal. These transporters are regulated by a zinc sensing transcription factor in the nuclear receptor family that we recently identified in a genetic screen. Low zinc homeostasis is mediated by a second family of transporters (ZIP) that import zinc into the cytoplasm. We are characterizing the transcriptional control of these transporters by low zinc. We discovered that one ZIP transporter mediates zinc signaling during sperm activation. We hope to understand how animals sense both high and low zinc and maintain homeostasis, and how zinc is used as a second messenger to transmit information during sperm activation.
The progressive, degenerative 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 ~18 days. We have characterized phenotypic changes that occur as worms age, and we have identified a class of anticonvulsant drugs and a hypertension medicine that delay age-related degeneration. We hope to define regulatory circuits that control aging and develop therapies that delay aging.
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 ultrabithorax 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 Developmental Biology, Washington University School of Medicine, 1995 – 2002.
Associate Professor, Department of Developmental Biology, Washinton University School of Medicine, 2002 – 2008
Professor, Department of Developmental Biology, Washington University School of Medicine, 2008 – present.
Honors and Awards
Medical Scientist Training Program Award, 1984 – 1991
Damon 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
Leukemia & Lymphoma Society Scholar Award, 2001 – 2006
Ellison Medical Foundation Senior Scholar Award, 2006 – 2010
Distinguished Educator Award, Washington University School of Medicine, 2014
- Warnhoff K, Roh HC, Kocsisova Z, Tan CH, Morrison A, Croswell D, Schneider DL, Kornfeld K. The Nuclear Receptor HIZR-1 Uses Zinc as a Ligand to Mediate Homeostasis in Response to High Zinc. PLoS Biol. 2017 Jan 17;15(1):e2000094. doi: 10.1371/journal.pbio.2000094.
- Dietrich N, Tan CH, Cubillas C, Earley BJ, Kornfeld K. Insights into zinc and cadmium biology in the nematode Caenorhabditis elegans.Arch Biochem Biophys. 2016 May 31.
- Kumar S, Dietrich N, Kornfeld K. Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span. PLoS Genet. 2016 Feb 26;12(2):e1005866.
- Warnhoff K, Kornfeld K. New links between protein N-terminal acetylation, dauer diapause, and the insulin/IGF-1 signaling pathway in Caenorhabditis elegans. Worm. 2015 Mar 11;4(2):e1023498.
- Leight ER, Murphy JT, Fantz DA, Pepin D, Schneider DL, Ratliff TM, Mohammad DH, Herman MA, Kornfeld K. 2015. Conversion of the LIN-1 ETS Protein of Caenorhabditis elegans from a Sumoylated Transcriptional Repressor to a Phosphorylated Transcriptional Activator. Genetics. 2015 Jan 7. pii: genetics.114.172668.
- Roh HC, Dimitrov I, Deshmukh K, Zhao G, Warnhoff K, Cabrera D, Tsai W, Kornfeld K. 2015. A modular system of DNA enhancer elements mediates tissue-specific activation of transcription by high dietary zinc in C. elegans. Nucleic Acids Res. 2015 Jan 30;43(2):803-16.
- Kumar S, Kocsisova Z, Kornfeld K. 2014. Keep on laying eggs Mama, RNAi my reproductive aging blues away. PLoS Genet. 2014 Dec 4;10(12):e1004808.
- Warnhoff K, Murphy JT, Kumar S, Schneider DL, Peterson M, Hsu S, Guthrie J, Robertson JD, Kornfeld K. 2014. The DAF-16 FOXO transcription factor regulates natc-1 to modulate stress resistance in Caenorhabditis elegans, linking insulin/IGF-1 signaling to protein N-terminal acetylation. PLoS Genet. 2014 Oct 16;10(10):e1004703.
- Pickett CL, Dietrich N, Chen J, Xiong C, Kornfeld K. 2013. Mated progeny production is a biomarker of aging in Caenorhabditis elegans. G3 (Bethesda). 2013 Dec 9;3(12):2219-32.
- Roh HC, Collier S, Deshmukh K, Guthrie J, Robertson JD, Kornfeld K. 2013. ttm-1 encodes CDF transporters that excrete zinc from intestinal cells of C. elegans and act in a parallel negative feedback circuit that promotes homeostasis. PLoS Genet. 2013 May;9(5):e1003522.
- Pickett CL, Kornfeld K. 2013. Age-related degeneration of the egg-laying system promotes matricidal hatching in Caenorhabditis elegans. Aging Cell. 2013 Aug;12(4):544-53.
- Roh HC, Collier S, Guthrie J, Robertson JD, Kornfeld K. 2012. Lysosome-related organelles in intestinal cells are a zinc storage site in C. elegans. Cell Metab. 2012 Jan 4;15(1):88-99.
- Hughes SE, Huang C, Kornfeld K. 2011. Identification of mutations that delay somatic or reproductive aging of Caenorhabditis elegans. Genetics. 2011 Sep;189(1):341-56.
- Murphy JT, Bruinsma JJ, Schneider DL, Collier S, Guthrie J, Chinwalla A, Robertson JD, Mardis ER, Kornfeld K. 2011. Histidine protects against zinc and nickel toxicity in Caenorhabditis elegans. PLoS Genet. 2011 Mar;7(3):e1002013. Epub 2011 Mar 24.
- Liu Z, Schneider DL, Kornfeld K, Kopan R. 2010. Simple copy number determination with reference query pyrosequencing (RQPS) .Cold Spring Harb Protoc. 2010 Sep 1;2010(9):pdb.prot5491. doi: 10.1101/pdb.prot5491.
- Davis, D. E., Roh, H. C., Deshmukh, K., Bruinsma, J. J., Schneider, D. L., Guthrie, J., Robertson, J. D.,and Kornfeld, K. 2009. The Cation Diffusion Facilitator Gene cdf-2Mediates Zinc Metabolism in Caenorhabditis elegans. Genetics, doi:10.1534/genetics.109.103614. (Abstract)
- Collins, J.J., Evason, K., Pickett, C.L., Schneider, D.L., and Kornfeld, K. 2008. The Anticonvulsant Ethosuximide Disrupts Sensory Function to Extend C. elegans Lifespan. PLoS Genetics, 4(10):e1000230. (Abstract)
- Bruinsma, J.J., Schneider D., Davis, D., and K. Kornfeld. 2008. Identification of mutations in Caenorhabditis elegans that cause resistance to high levels of dietary zinc and analysis using a genome-wide map of single-nucleotide polymorphisms scored by pyrosequencing. Genetics, 179: 811-828. (Abstract)
- Evason, K., Collins, J.J., Huang, C., Hughes, S., and K. Kornfeld. 2008. Valproic acid extends C. elegans lifespan. Aging Cell, 7: 305-317. (Abstract)
- Collins, J.J., C. Huang, S. Hughes and K. Kornfeld. 2007. The measurement and analysis of age-related changes in Caenorhabditis elegans. WormBook, ed. The C. elegans Research Community, WormBook, http://www.wormbook.org (Abstract)
- Hughes, S., K. Evason, C. Xiong and K. Kornfeld. 2007. Genetic and pharmacological factors that influence reproductive aging in nematodes. PLoS Genetics, 3(2): 254-265. (Abstract)
- Collins, J.J., K. Evason and K. Kornfeld. 2006. Pharmacology of delayed aging and extended lifespan of Caenorhabditis elegans. Experimental Gerontology 41: 1032-1039. (Abstract)
- Evason, K., and K. Kornfeld. 2006. Effects of anticonvulsant drugs on lifespan. Archives of Neurology, 63: 491-496. (Abstract)
- Evason, K., C. Huang, I. Yamben, D.F. Covey and K. Kornfeld. 2005. Anticonvulsant medications extend worm life-span. Science 307: 258-262. (Abstract)
- Leight, E., D. Glossip, and K. Kornfeld. 2005. Sumoylation of LIN-1 promotes transcriptional repression and inhibition of vulval cell fates. Development 132: 1047-1056. (Abstract)
- Huang, C., C. Xiong and K. Kornfeld. 2004. Measurements of age-related changes of physiological processes that predict life span of Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA., 101: 8084-8089. (Abstract)
- Bruinsma, J. J., T. Jirakulaporn, A. J. Muslin and K. Kornfeld. 2002. Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling. Developmental Cell 2: 567-578. (Abstract)
- Fantz, D.A., D. Jacobs, D. Glossip and K. Kornfeld. 2001. Docking sites on substrate proteins direct extracellular-signal regulated kinase to phosphorylate specific residues. J. Biol. Chem. 276: 27256-27265. (Abstract)
- Jacobs, D., D. Glossip, H. Xing, A.J. Muslin and K. Kornfeld. 1999. Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase. Genes & Development 13:163-175. (Abstract)
- Kornfeld, K. 1997. Vulval development in Caenorhabditis elegans. Trends in Genetics 13: 55-61. (Abstract)
- Kornfeld, K., D.B. Hom and H.R. Horvitz. 1995. The ksr-1 gene encodes a novel protein kinase involved in Ras-mediated signaling in C. elegans. Cell 83: 903-913. (Abstract)