Doris E. Kretzschmar, Ph.D.
- 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
Biography
We are using Drosophila to study basic mechanisms of neurodegeneration. Currently, we are focusing on two proteins that play key roles in Alzheimer’s disease; the Amyloid Precursor Protein and Tau. We are investigating what effects disease-associated changes in these proteins have on their functions and how this effects the genetic pathways these proteins are involved in. To address this, we use behavioral assays, histology and confocal imaging, as well as various molecular and sequencing techniques. Using genetic manipulations, we study whether other proteins can ameliorate disease-associated phenotypes or contribute to the pathogenicity. In a second project, we are investigating effects of aging on behavior and the function of the nervous system. In addition, my group is part of a research center that tests effects of botanical dietary supplements on enhancing resilience during aging and in neurodegenerative diseases.
Education and training
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Degrees
- Ph.D., 1991, Univeristy of Würzburg
Additional information
Publications
Selected publications
- Nash, T.R., Chow, E.S., Law, A.D., Fu S.D., Fuszara E., Biska A., Bebas P., Kretzschmar, D., Giebultowicz, J.M. Daily blue-light exposure shortens lifespan and causes brain neurodegeneration in Drosophila. npj Aging and Mechanisms of Disease. 2019 Dec. 5(1), 8
- Sunderhaus, E.R., Law, A.D., Kretzschmar, D. Disease-Associated PNPLA6 Mutations Maintain Partial Functions When Analyzed in Drosophila. Frontiers in Neuroscience. 2019 Nov. 13,1207
- Sunderhaus ER, Law AD, Kretzschmar D. ER responses play a key role in Swiss-Cheese/Neuropathy Target Esterase-associated neurodegeneration. Neurobiology of Disease. 2019 June 130,104520.
- Rieche F, Carmine-Simmen K, Poeck B, Kretzschmar D, Strauss R. Drosophila Full-Length Amyloid Precursor Protein Is Required for Visual Working Memory and Prevents Age-Related Memory Impairment. Curr Biol. 2018 Mar 5;28(5):817-823.
- Cassar M, Sunderhaus E, Wentzell JS, Kuntz S, Strauss R, Kretzschmar D. The PKA-C3 catalytic subunit is required in two pairs of interneurons for successful mating of Drosophila. Sci Rep. 2018 Feb 6;8(1):2458.
- Reduced Expression of Foxp1 as a Contributing Factor in Huntington's Disease. Louis Sam Titus ASC, Yusuff T, Cassar M, Thomas E, Kretzschmar D, D'Mello SR. J Neurosci. 2017 Jul 5;37(27):6575-6587.
- McFerrin J, Patton BL, Sunderhaus ER, Kretzschmar D. NTE/PNPLA6 is expressed in mature Schwann cells and is required for glial ensheathment of Remak fibers. Glia. 2017 May;65(5):804-816. PMCID:PMC5357176.
- Ramaker JM, Cargill RS, Swanson TL, Quirindongo H, Cassar M, Kretzschmar D, Copenhaver PF. Amyloid Precursor Proteins Are Dynamically Trafficked and Processed during Neuronal Development.Front Mol Neurosci. 2016 Nov 25;9:130.
- Sunderhaus E., Kretzschmar D. Mass histology to quantify neurodegeneration in Drosophila. JOVE,2016 Dec 15.
- Dutta S, Rieche F, Eckl N, Duch C, Kretzschmar D. Glial expression of Swiss cheese (SWS), the Drosophila orthologue of neuropathy target esterase (NTE), is required for neuronal ensheathment and function. Dis Model Mech. 2016 9(3):283-94. PMID: 26634819
Publications
Centella asiatica and its caffeoylquinic acid and triterpene constituents increase dendritic arborization of mouse primary hippocampal neurons and improve age-related locomotion deficits in Drosophila
Frontiers in AgingThe amyloid precursor protein intracellular domain induces sleep disruptions and its nuclear localization fluctuates in circadian pacemaker neurons in Drosophila and mice
Neurobiology of DiseaseChlorogenic Acids, Acting via Calcineurin, Are the Main Compounds in Centella asiatica Extracts That Mediate Resilience to Chronic Stress in Drosophila melanogaster
NutrientsChronic blue light leads to accelerated aging in Drosophila by impairing energy metabolism and neurotransmitter levels
Frontiers in AgingDeveloping a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials
Frontiers in NutritionFTD-associated mutations in Tau result in a combination of dominant and recessive phenotypes
Neurobiology of DiseaseWithania somnifera and Centella asiatica Extracts Ameliorate Behavioral Deficits in an In Vivo Drosophila melanogaster Model of Oxidative Stress
AntioxidantsWithania somnifera Extracts Promote Resilience against Age-Related and Stress-Induced Behavioral Phenotypes in Drosophila melanogaster; a Possible Role of Other Compounds besides Withanolides
NutrientsMitochondrial Redox Signaling Is Critical to the Normal Functioning of the Neuronal System
Frontiers in Cell and Developmental BiologyDisease-Associated Mutant Tau Prevents Circadian Changes in the Cytoskeleton of Central Pacemaker Neurons
Frontiers in NeuroscienceLactate dehydrogenase expression modulates longevity and neurodegeneration in Drosophila melanogaster
AgingDaily blue-light exposure shortens lifespan and causes brain neurodegeneration in Drosophila
npj Aging and Mechanisms of DiseaseDisease-Associated PNPLA6 Mutations Maintain Partial Functions When Analyzed in Drosophila
Frontiers in NeuroscienceER responses play a key role in Swiss-Cheese/Neuropathy Target Esterase-associated neurodegeneration
Neurobiology of DiseaseDrosophila Full-Length Amyloid Precursor Protein Is Required for Visual Working Memory and Prevents Age-Related Memory Impairment
Current BiologyThe PKA-C3 catalytic subunit is required in two pairs of interneurons for successful mating of Drosophila
Scientific ReportsNTE/PNPLA6 is expressed in mature Schwann cells and is required for glial ensheathment of Remak fibers
GLIAReduced expression of foxpl as a contributing factor in huntington’s disease
Journal of NeuroscienceAmyloid precursor proteins are dynamically trafficked and processed during neuronal development
Frontiers in Molecular NeuroscienceGlial expression of Swiss cheese (SWS), the Drosophila orthologue of neuropathy target esterase (NTE), is required for neuronal ensheathment and function
DMM Disease Models and MechanismsMass histology to quantify neurodegeneration in drosophila
Journal of Visualized ExperimentsManipulations of amyloid precursor protein cleavage disrupt the circadian clock in aging Drosophila
Neurobiology of DiseaseMutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness
Nature communicationsIncreased actin polymerization and stabilization interferes with neuronal function and survival in the AMPKγ mutant loechrig
PloS oneLoss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome
Journal of Clinical Endocrinology and MetabolismLoss of tau results in defects in photoreceptor development and progressive neuronal degeneration in Drosophila
Developmental Neurobiology