Davis Laboratory

The Davis Lab is focused on understanding mechanisms underlying the pathogenesis of Parkinson’s disease (PD) and other neurodegenerative diseases through the use of Drosophila and human neuronal cell culture models, combined with human genetic and clinical data.  In collaboration with the Pacific Northwest Udall Center and Parkinson’s Genetic Research Study, we have found that GBA variants not only increase the risk of developing PD but also accelerate motor and cognitive decline in PD patients. We are currently investigating the mechanisms underlying this faster disease progression, and hypothesize that GBA variants alter lipid metabolism, leading to alterations in endocytic trafficking, autophagy, and cell-to-cell propagation of pathogenic protein aggregation via extracellular vesicles. To test this hypothesis, we are using a GBA deficient Drosophila model that manifests neurodegeneration, motor and cognitive dysfunction, and accelerated protein aggregation. We are also using iPSC-derived human neurons from a PD patient heterozygous for a null GBA mutation. We hope to validate our findings from our in vitro and Drosophila models in longitudinal PD cohorts, and explore potential new therapeutic targets.

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Lab Members

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Publications

Jewett KA, Thomas RE, Phan CQ, Lin B, Milstein G, Yu S, Bettcher LF, Neto FC, Djukovic D, Raftery D, Pallanck LJ, Davis MY. Glucocerebrosidase reduces the spread of protein aggregation in a Drosophila melanogaster model of neurodegeneration by regulating proteins trafficked by extracellular vesicles. PLoS Genet 2021 Feb 4;17(2):e1008859. doi: 10.1371/journal.pgen.1008859. PMID: 33539341

Kim HM, Leverenz JB, Burdick DJ, Srivatsal S, Pate J, Hu S, Millard S, Davis M, Samii A, Zabetian CP. Diagnostic Validation for Participants in the Washington State Parkinson Disease Registry. Parkinson’s Disease, 2018; 1-6. PMID: 30515290

Thomas RE, Vincow ES, Merrihew GE, MacCoss MJ, Davis MY, Pallanck LJ. Glucocerebrosidase deficiency promotes protein aggregation through dysregulation of extracellular vesicles. PLoS Genetics, 2018; 14(9):e1007694. PMID: 30256786

Tsuang DW, Greenwood TA, Jayadev S, Davis M, Shutes-David A, Bird TD. A Genetic Study of Psychosis in Huntington’s Disease: Evidence for the involvement of Glutamate Signaling Pathways. Journal of Huntington’s disease. 2018; 7(1):51-59. PMID: 29480208

Latimer CS, Flanagan ME, Cimino PJ, Jayadev S, Davis M, Hoffer ZS, Montine TJ, Gonzalez-Cuyar LF, Bird TD, Keene CD. Neuropathological Comparison of Adult Onset and Juvenile Huntington’s Disease with Cerebellar Atrophy: A Report of a Father and Son. Journal of Huntington’s disease, 2017; 6(4):337-348. PMID: 29036832

Davis MY, Johnson CO, Leverenz JB, Weintraub D, Trojanowski JQ, Chen-Plotkin A, Van Deerlin VM, Quinn JF, Chung KA, Peterson-Hiller AL, Rosenthal LS,Dawson TM, Albert MS, Goldman JG, Stebbins GT, Bernard B, Wszolek KZ, Ross OA, Dickson DW, Eidelberg D, Mattis PJ, Niethamme M, Yearout D, Hu S, Cholerton BA, Smith M, Mata IF, Montine TJ, Edwards KL, Zabetian CP. Association of GBA mutations and the E326K Polymorphism With Motor and Cognitive Progression in Parkinson Disease. JAMA Neurology, 2016. PMID: 27571329

Mata IF, Davis MY, Lopez AN, Dorschner MO, Martinez E, Yearout D, Cholerton BA, Hu SC, Edwards KL, Bird TD, Zabetian CP. The Discovery of LRRK2 p.R14441S, a novel mutation for Parkinson’s disease, adds to the complexity of a mutational hotspot. American Journal of Medical Genetics. PartB, Neuropsychiatric Genetics, 2016. PMID: 27111571

Domoto-Reilly K, Davis MY, Keene CD, Bird TD. Unusually long duration and delayed penetrance in a family with FTD and mutation in MAPT (V337M). American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 2016. PMID: 26990251

Davis MY, Trinh K, Thomas RE, Yu S, Germanos AA, Whitley B, Sardi SP, Montine TJ, Pallanck LJ. Glucocerebrosidase deficiency in Drosophila results in α-synuclein-independent protein aggregation and neurodegeneration. PLoS Genetics, 2016; 12(3):e1005944. PMID: 27019408

Chen D, Meneret A, Friedman JR, Korvatska O, Gad A, Bonkowski ES, Stessman H, Doummar D, Mignot C, Anheim M, Bernes S, Davis MY, Damon-Perriere N, Degos B, Grabli D, Gras D, Hisama FM, Mackenzie KM, Swanson PD, Tranchant C, Vidailhet M, Winesett S, Trouillard O, Amendola LM, Dorschner MO, Weiss M, Eichler EE, Torkamani A, Roze E, Bird TD, Raskind WH. ADCY5-related dyskinesia: Broader spectrum and genotype-phenotype correlations. Neurology 2015; 85(23):2026-35. PMID: 26537056

DavisMY, Keene CD, Jayadev S, Bird TD.  The Co-Occurrence of Alzheimer’s Disease and Huntington’s Disease: a neuropathological study of 15 elderly Huntington’s Disease subjects. Journal of Huntington’s Disease 2014;3(2):209-17. PMID: 25062863

DavisMY, Keene CD, Swanson PD, SheehyC, Bird TD.  Novel mutations in ataxia telangiectasia and AOA2 associated with prolonged survival. Journal of Neurologic Sciences 2013 December;335(1-2):134-138. PMID: 24090759

Mandler R, Kobayashi H, Davis MY, Waldmann TA, and Brechbiel, MW. Modifications in synthesis strategy improve the yield and efficacy of geldanamycin-herceptin immunoconjugates. Bioconjuguate Chemistry 2002 Jul-Aug;13(4):786-91. PMID: 12121134

KluenemannHH, Nutt JG, Davis MY, BirdTD.Parkinsonian Syndrome in Heterozygotes for Niemann Pick C. Journal of Neurological Sciences 2013 December;335(1-2):219-220. PMID: 24035292

Zamparini AL*, Davis MY*, Malone CD, Vieira E, Zavadil J, Sachidanandam R, Hannon GJ, Lehmann R.  Vreteno, a gonad-specific protein, is essential for germline development and primary piRNA biogenesis in Drosophila. Development 2011 Sep;138(18):4039-50.  *Co-first author with equal contribution.    PMID: 21831924

Oakes PK, Srivatsal SR, Davis MY, Samii A. Movement Disorders in Multiple Sclerosis. Physical Medicine and Rehabilitation Clinics of North America 2013;24(4):639-651. PMID: 24314682

Chen, D, NaydenovA, BlankmanJL, MeffordHC, DavisM, SulY, BarloonAS, BonkowskiE, WolffJ, MatsushitaM, SmithC, CravattBF, Mackie K, Raskind WH, StellaN, and Bird TD.  Two Novel Mutations in ABHD12: Expansion of the Mutation Spectrum in PHARC and Assessment of their Functional Effects. Human Mutation 2013 December;34(12):1672-8. PMID: 24027063