Photo of Doris E. Kretzschmar, Ph.D.

Doris E. Kretzschmar Ph.D.

  •      (503) 494-0243
    • Associate Professor Oregon Institute of Occupational Health Sciences
    • Associate Professor of Molecular and Medical Genetics School of Medicine
    • Molecular and Medical Genetics Graduate Program School of Medicine
    • Neuroscience Graduate Program School of Medicine
    • Program in Molecular and Cellular Biosciences School of Medicine

We are using Drosophila to study basic mechanisms of neurodegeneration. Currently, we are focusing on two projects. One is the characterization of the swiss cheese mutant, which shows progressive degeneration of the adult nervous system. SWS is the fly homolog of a ´human gene called Neuropathy Target Esterase which plays a role in neurodegeneration induced by pesticides and nerve agents.  Recent results indicated that SWS/NTE interfere with membrane composition thereby damaging neurons.  We are now studying in detail how this leads to neuronal degeneration and cell death.  The other project focuses on the function of Amyloid Precursor Proteins, which are key factors in Alzheimer's Disease.  We are investigating how these proteins are processed , what function different fragments derived from this large precursor protein have, and what other genes influence these processes.  In addition, we have developed a system to study the transport of this protein and its fragments in the living brain using confocal imaging.

Education

  • Ph.D., Univeristy of Wüerzburg, Wüerzburg Germany 1999

Publications

  • "Swiss cheese, a protein involved in progressive neurodegeneration, acts as a noncanonical regulatory subunit for PKA-C3" Journal of Neuroscience October 22 2008
  • "Avian cellular homolog of the qin oncogene" Proceedings of the National Academy of Sciences of the United States of America January 17 1995
  • "Progressive neurodegeneration in Drosophila" Journal of Neural Transmission, Supplement  2003
  • "The neurodegeneration mutant löchrig interferes with cholesterol homeostasis and Appl processing" EMBO Journal December 2 2002
  • "Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness" Nature Communications January 8 2015
  • "Cloning and expression of the murine sws/NTE gene" Mechanisms of Development February 1 2000
  • "Deregulation of the Egfr/Ras signaling pathway induces age-related brain degeneration in the Drosophila mutant vap" Molecular Biology of the Cell January 1 2003
  • "Mutations in gamma adducin are associated with inherited cerebral palsy" Annals of Neurology December 2013
  • "Optomotor-blind expression in glial cells is required for correct axonal projection across the Drosophila inner optic chiasm" Developmental Biology March 1 2008
  • "Increased actin polymerization and stabilization interferes with neuronal function and survival in the AMPKγ mutant loechrig" PLoS One February 25 2014
  • "Disruption of the MAP1B-related protein FUTSCH leads to changes in the neuronal cytoskeleton, axonal transport defects, and progressive neurodegeneration in Drosophila" Molecular Biology of the Cell May 2005
  • "Models of Alzheimer's Disease"  July 2013
  • "Neurotoxic effects induced by the Drosophila amyloid-β peptide suggest a conserved toxic function" Neurobiology of Disease February 2009
  • "Alzheimer's Disease and tauopathy studies in flies and worms" Neurobiology of Disease October 2010
  • "Analysis of amyloid precursor protein function in Drosophila melanogaster" Experimental Brain Research April 2012
  • "Increased RhoA Prenylation in the loechrig (loe) Mutant Leads to Progressive Neurodegeneration" PLoS One September 6 2012
  • "Organophosphate-induced changes in the PKA regulatory function of Swiss Cheese/NTE lead to behavioral deficits and neurodegeneration" PLoS One February 18 2014
  • "Glia in development, function, and neurodegeneration of the adult insect brain" Brain Research Bulletin January 1 2002
  • "Loss of circadian clock accelerates aging in neurodegeneration-prone mutants" Neurobiology of Disease March 2012
  • "Swiss cheese et allii, some of the first neurodegenerative mutants isolated in Drosophila" Journal of Neurogenetics March 2009
  • "A translational continuum of model systems for evaluating treatment strategies in Alzheimer's disease" DMM Disease Models and Mechanisms September 2011
  • "Giant lens, a gene involved in cell determination and axon guidance in the visual system of Drosophila melanogaster" EMBO Journal  1992
  • "Manipulations of amyloid precursor protein cleavage disrupt the circadian clock in aging Drosophila" Neurobiology of Disease May 1 2015
  • "Drosophila GGA Model" Traffic December 2011
  • "The circadian clock gene period extends healthspan in aging Drosophila melanogaster." Aging November 2009
  • "The Swiss cheese mutant causes glial hyperwrapping and brain degeneration in Drosophila" Journal of Neuroscience  1997
  • "Defective pigment granule biogenesis and aberrant behavior caused by mutations in the Drosophila AP-3β adaptin gene ruby" Genetics May 2000
  • "Amyloid precursor proteins are protective in Drosophila models of progressive neurodegeneration" Neurobiology of Disease April 2012
  • "Identification of novel 1,4-benzoxazine compounds that are protective in tissue culture and in vivo models of neurodegeneration" Journal of Neuroscience Research July 2010
  • "The Drosophila carbonyl reductase sniffer prevents oxidative stress-induced neurodegeneration" Current Biology May 4 2004

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