Doris Kretzschmar, Ph.D.
- Associate Professor, Oregon Institute of Occupational Health Sciences
- Associate Professor, Molecular & Medical Genetics
- RJH 2586
Summary of Current Research
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.
1. Relationships between the circadian system and Alzheimer's disease-like symptoms in Drosophila;
Long DM, Blake MR, Dutta S, Holbrook SD, Kotwica-Rolinska J, Kretzschmar D, Giebultowicz JM.
PLoS One. 2014 Aug 29;9(8):e106068. doi: 10.1371 eCollection 2014
2. Loss-of-Function Mutations in PNPLA6 Encoding Neuropathy Target Esterase Underlie Pubertal Failure and Neurological Deficits in Gordon Holmes Syndrome; Topaloglu AK, Lomniczi A, Kretzschmar D, Dissen GA, Kotan LD, McArdle CA, Koc AF, Hamel BC, Guclu M, Papatya ED, Eren E, Mengen E, Gurbuz F, Cook M, Castellano JM, Kekil MB, Mungan NO, Yuksel B, Ojeda SR. J Clin Endocrinol Metab. 2014 Oct;99(10):E2067-75. doi: 10.1210 Epub 2014 Jul 17.
3. Loss of tau results in defects in photoreceptor development and progressive neuronal degeneration in Drosophila; Bolkan BJ, Kretzschmar D. Dev Neurobiol. 2014 Jun 7. doi: 10.1002
4. Increased actin polymerization and stabilization interferes with neuronal function and survival in the AMPKγ mutant Loechrig; Cook M, Bolkan BJ, Kretzschmar D. PLoS One. 2014 Feb 25;9(2):e89847. doi: 10.1371
5. Organophosphate-induced changes in the PKA regulatory function of Swiss Cheese/NTE lead to behavioral deficits and neurodegeneration; Wentzell JS, Cassar M, Kretzschmar D. PLoS One. 2014 Feb 18;9(2):e87526. doi: 10.1371 eCollection 2014.
6. Mutations in γ adducin are associated with inherited cerebral palsy; Kruer MC, Jepperson T, Dutta S, Steiner RD, Cottenie E, Sanford L, Merkens M, Russman BS, Blasco PA, Fan G, Pollock J, Green S, Woltjer RL, Mooney C, Kretzschmar D, Paisán-Ruiz C, Houlden H. Ann Neurol. 2013 Dec;74(6):805-14.
Ph.D. Univeristy of Wüerzburg, Germany