Mathews Lab
Head of Lab
Paul Mathews, PhDThe Mathews’ lab examines cell biological events that contribute to neurodegenerative diseases. Our focus is on understanding how alterations in intracellular vesicle trafficking and the expression and movement of specific membrane proteins from the plasma membrane into the endosomal-lysosomal system impact the progression of neurodegenerative disorders. This includes modulation of amyloid precursor protein (APP) intracellular distribution and trafficking, the proteolytic systems that contribute to its metabolism, the impact of disease risk-factors on these events and systems, and, ultimately, the role various APP metabolites play both in normal function of the brain and during pathological processes. In support of these studies, our group has extensively developed the capabilities needed to analyze APP metabolites in the mouse brain. In addition to examining disease-driving changes in neuronal endocytosis and APP metabolism in mouse modes of Down syndrome and other early-onset AD-related transgenic models, the group studies the impact of the three human apolipoprotein E (APOE) alleles on the early endosome. These studies have identified early events impacting endosomal pathway function that are both prior to and independent of the hallmark AD pathologies of β-amyloid and tau accumulation. The Mathews’ laboratory collaborates extensively with other laboratories in the CDR in our studies of the endosomal-lysosomal system, working to jointly delineate dysfunctions throughout this interconnected system that contribute to neuronal vulnerability and disease progression.
Selected Publications
Peng KY, Pérez-González R, Alldred MJ, Goulbourne CN, Morales-Corraliza J, Saito M, Saito M, Ginsberg SD, Mathews PM, Levy E. Apolipoprotein E4 genotype compromises brain exosome production. Brain. 2019 Jan 1;142(1):163-175. doi: 10.1093/brain/awy289. PMID: 30496349; PMCID: PMC6308312.
Morales-Corraliza J, Wong H, Mazzella MJ, Che S, Lee SH, Petkova E, Wagner JD, Hemby SE, Ginsberg SD, Mathews PM. Brain-Wide Insulin Resistance, Tau Phosphorylation Changes, and Hippocampal Neprilysin and Amyloid-β Alterations in a Monkey Model of Type 1 Diabetes. J Neurosci. 2016 Apr 13;36(15):4248-58. doi: 10.1523/JNEUROSCI.4640-14.2016. PMID: 27076423; PMCID: PMC4829649.
Morales-Corraliza J, Schmidt SD, Mazzella MJ, Berger JD, Wilson DA, Wesson DW, Jucker M, Levy E, Nixon RA, Mathews PM. Immunization targeting a minor plaque constituent clears β-amyloid and rescues behavioral deficits in an Alzheimer's disease mouse model. Neurobiol Aging. 2013 Jan;34(1):137-45. doi: 10.1016/j.neurobiolaging.2012.04.007. Epub 2012 May 18. PMID: 22608241; PMCID: PMC3426627.
Publications
All publications
Mathews Lab Members
Kathy Peng, PhD Postdoctoral Researcher 845-398-7751 Kathy.Peng@NKI.rfmh.org |
 Braison Liemisa Research Support Assistant 845-398-5439 Braison.Liemisa@NKI.rfmh.org |
 Jonathan Pasato Research Support Assistant 845-398-5439 Jonathan.Pasato@nki.rfmh.org |