Dr. Singleton's postdoc research addresses the role of mitophagy in mitochondrial retention seen in Menkes disease, a progressive form of childhood neurodegeneration that is triggered by dysregulation of copper which shares pathogenic mechanisms with neurodevelopmental disorders. She is testing the hypothesis that deficits in ATP7A, a chief transporter required for copper homeostasis, activates the pink-parkin mitophagy pathway in order to trap damaged mitochondria within the soma, thus preventing mitochondria delivery to the synapse in Menkes disease.
Dr. Singleton's ultimate research goal is to use systems biology and genetic approaches combined with her training in cellular and molecular neuroscience to investigate the mechanisms that control neuron development in normal and pathological conditions.
Foundation of the Singleton Lab
Anticipated in 2024
Lee CE, Singleton KS, Wallin M, Faundez VF. Rare Genetic Diseases, Nature’s Experiment on Human Development. iScience. May 2020. https://doi.org/10.1016/j.isci.2020.101123
Singleton KS, Silva PR, Silva EM. Pairing your Sox: Identification of Sox11 partner proteins and interaction domains in the developing neural plate. Submitted to Journal of Biological Chemistry, 2020. bioRxiv:
Larimore J, Zlatic SA, Arnold M, Singleton KS, Cross R, Rudolph H, Bruegge MV, Sweetman A, Garza C, Whisnant E and Faundez V. Dysbindin Deficiency Modifies the Expression of GABA Neuron and Ion Permeation Transcripts in the Developing Hippocampus. Front. Genet. 2017 8:28. doi: 10.3389/fgene.2017.00028
Rudolph H., Cross RD., Segura L, Singleton KS., Larimore, J. Neuronal Endosomal Trafficking: One of the common molecular Pathways Disrupted in Autism Spectrum Disorders and Schizophrenia. Journal of Neurology and Psychology. ISSN: 2332-3469
Arnold M*, Singleton KS*, Cross RD, Chapleau D, Mullin AP, Rolle I, Moore C, Theibert A, Pozzo-Miller L, Faundez V, Larimore J. The Endosome Localized AGAP1 Modulates Spine Morphology Downstream of the Neurodevelopmental Disorder Factor Dysbindin. Frontiers in Cellular Neuroscience. 2016 September. Doi: http://dx.doi.org/10.3389/fncel.2016.00218
*Authors contributed to this work equally
Kalidindi A, Kelly SD, Singleton KS, Guzman D, Merrill L, Willard SL, Shively CA, Neigh GN. Reduced marker of vascularization in the anterior hippocampus in a female monkey model of depression. Physiol Behav. 2016 Jul 14. pii: S0031-9384(16)30530-3. doi: 10.1016/j.physbeh.2016.07.007. PubMed PMID: 27423324
Larimore J, Zlatic SA, Gokhale A, Tornieri K, Singleton KS, Mullin AP, Tang J, Talbot K, Faundez V. Mutations in the BLOC-1 Subunits Dysbindin and Muted Generate Divergent and Dosage-Dependent Phenotypes. J Biol Chem. 2014 Apr 8. PMID: 24713699