S. Kerry Kornfeld, M.D., Ph.D.

Professor
Developmental Biology

Developmental, Regenerative and Stem Cell Biology Program
Molecular Genetics and Genomics Program
Molecular Cell Biology Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-747-1480

  • 314-747-2004

  • 314-747-2003

  • 314-362-7058

  • 8103

  • 3607 Cancer Research Building

  • kornfeld@wustl.edu

  • http://kornfeldlab.wustl.edu

  • aging, metals, zinc, development, sperm activation, signal transduction, homeostasis

  • organismal aging; zinc homeostasis and roles of zinc during cell differentiation.

Research Abstract:

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.

Selected Publications:

Kumar S, N. Dietrich and K. Kornfeld. 2016. Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span. PLoS Genet. 12(2):e1005866. PMID: 26918946

Roh, H.C., I. Dimitrov, K. Deshmukh, G. Zhao, K. Warnhoff, D. Cabrera, W. Tsai, and K. Kornfeld. 2015. A modular system of DNA enhancer elements mediates tissue-specific activation of transcription by high dietary zinc in C. elegans. Nucleic Acids Research, 43(2):803-16.

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.199(3):761-75.

Pickett, C.L. and K. Kornfeld. 2013. Age-related degeneration of the egg-laying system promotes matricidal hatching in Caenorhabditis elegans. Aging Cell. doi:10.1111/acel.12079.

Roh, H. C., S. Collier, K. Deshmukh, J. Guthrie, J. D. Robertson and K. Kornfeld. 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, 9(5):e1003522.

Roh H, Collier S, Guthrie J, Robertson JD and Kornfeld K. Lysosome-related organelles in intestinal cells are a zinc storage site in C. elegans. Cell Metabolism 2012 15:88-99.

Murphy JT, Bruinsma JJ, Schneider DL, Collier S, Guthrie J, Chinwalla A, Robertson JD, Mardis ER and Kornfeld K. Histidine protects against zinc and nickel toxicity in C. elegans. PLoS Genet 2011 7(3): e1002013. doi:10.1371/journal.pgen.1002013

Collins JJ, Evason K, Pickett CL, Schneider DL and Kornfeld K. The Anticonvulsant Ethosuximide Disrupts Sensory Function to Extend C. elegans Lifespan. PLoS Genetics 2008 4(10):e1000230. (Abstract)

Hughes S, Evason K, Xiong C and Kornfeld K. Genetic and pharmacological factors that influence reproductive aging in nematodes. PLoS Genetics 2007 3(2): 254-265. (Abstract)

Evason K, Huang C, Yamben I, Covey DF and Kornfeld K. Anticonvulsant medications extend worm life-span. Science 2005 307: 258-262. (Abstract)

Last Updated: 11/4/2016 9:35:50 AM

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