S. Kerry Kornfeld, MD, PhD

Research interests

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

Dean’s Impact Award, Washington University School of Medicine, 2023

Selected publications

• Tan CH, Kornfeld K. Zinc is an intracellular signal during sperm activation in Caenorhabditis elegans. Development. 2021 Nov 1;148(21):dev199836
• Earley BJ, Cubillas C, Warnhoff K, Ahmad R, Alcantar A, Lyon MD, Schneider DL, Kornfeld K. Cadmium hijacks the high zinc response by binding and activating the HIZR-1 nuclear receptor. Proc Natl Acad Sci U S A. 2021 Oct 19;118(42):e2022649118
• Kumar S, Egan BM, Kocsisova Z, Schneider DL, Murphy JT, Diwan A, Kornfeld K. Lifespan Extension in C. elegans Caused by Bacterial Colonization of the Intestine and Subsequent Activation of an Innate Immune Response. Dev Cell. 2019 Apr 8;49(1):100-117.e6
• Kocsisova Z, Kornfeld K, Schedl T. Rapid population-wide declines in stem cell number and activity during reproductive aging in C. elegans. Development. 2019 Apr 23;146(8):dev173195
• Zhao Y, Tan CH, Krauchunas A, Scharf A, Dietrich N, Warnhoff K, Yuan Z, Druzhinina M, Gu SG, Miao L, Singson A, Ellis RE, Kornfeld K. The zinc transporter ZIPT-7.1 regulates sperm activation in nematodes. PLoS Biol. 2018 Jun 7;16(6):e2005069.
• Dietrich N, Schneider DL, Kornfeld K. A pathway for low zinc homeostasis that is conserved in animals and acts in parallel to the pathway for high zinc homeostasis. Nucleic Acids Res. 2017 Nov 16;45(20):11658-11672.
• 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
• Kumar S, Dietrich N, Kornfeld K. Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span. PLoS Genet. 2016 Feb 26;12(2):e1005866
• Roh HC, Dimitrov I, Deshmukh K, Zhao G, Warnhoff K, Cabrera D, Tsai W, Kornfeld K. 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;43(2):803-16
• Roh HC, Collier S, Guthrie J, Robertson JD, Kornfeld K. 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, Evason K, Xiong C, Kornfeld K. Genetic and pharmacological factors that influence reproductive aging in nematodes. PLoS Genet. 2007 Feb 16;3(2):e25
• Leight ER, Glossip D, Kornfeld K. Sumoylation of LIN-1 promotes transcriptional repression and inhibition of vulval cell fates. Development. 2005 Mar;132(5):1047-56
• Evason K, Huang C, Yamben I, Covey DF, Kornfeld K. Anticonvulsant medications extend worm life-span. Science. 2005 Jan 14;307(5707):258-62
• Huang C, Xiong C, Kornfeld K. Measurements of age-related changes of physiological processes that predict lifespan of Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2004 May 25;101(21):8084-9
• Bruinsma JJ, Jirakulaporn T, Muslin AJ, Kornfeld K. Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling. Dev Cell. 2002 May;2(5):567-78
• Jacobs D, Glossip D, Xing H, Muslin AJ, Kornfeld K. Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase. Genes Dev. 1999 Jan 15;13(2):163-75

See a complete list of Dr. Kornfeld’s publications »