Department of Molecular and Cellular Biology
Become enchanted with the neuronal cytoskeleton! The goal of my lab is to understand the complex kinase pathways that regulate the cytoskeleton during neuronal development and maintenance. When perturbed, a number of these kinase pathways lead to neurodevelopmental or neurodegenerative disease, as is the case with Dyrk1a/MNB, a primary focus of my lab. Dyrk1a is a Down Syndrome critical kinase, and other mutations within the kinase have been linked to Autism Spectrum Disorders and other neurodevelopmental disorders. Our lab uses genomic engineering combined with live imaging techniques within the model organism, Drosophila melanogaster, to understand the role of kinases in organizing the microtubule cytoskeleton in vivo. In addition, we use a range of chemical genetic and biochemical techniques to dissect the pathway of these kinases and their molecular substrates in vitro. We are also beginning to perform larval behavioral assays in order to understand how changes in the cytoskeleton of a neuron contribute to neuronal function. Understanding how a kinase contributes to neuronal architecture and activity on a molecular level will provide valuable insights into the cause and progression of a number of neurological disorders.
How is the cytoskeleton organized and regulated in order to produce a distinct neuronal morphology?
How does phosphorylation of tubulin affects its ability to polymerize into microtubules?
How does the Down Syndrome critical kinase, MNB/DYRK1a, regulate the microtubule cytoskeleton directly or indirectly during neuronal development and maintenance?
How is MNB/DYRK1a regulated both temporally and spatially within a cell?
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
Specialties / Focus
- Cell Biology
- Developmental Biology
- Molecular Genetics
- MCB 160L Principles of Genetics Laboratory, Winter
Honors and Awards
- NIH K99/R00 Pathway to Independence Award (NICHD)
- March of Dimes Basil O'Connor Starter Scholar Research Award
- Jane Coffin Childs Postdoctoral Fellowship
- Simons Foundation Autism Research Initiative Pilot Award
- 2011 PhD Biological Sciences Columbia University
- 2005 BA Neuroscience and Behavior Vassar College
Ori-McKenney KM, McKenney RJ, Huang HH, Li T, Meltzer S, Jan LY, Vale RD, Wiita AR, Jan YN. Phosphorylation of β-Tubulin by the Down Syndrome Kinase, Minibrain/DYRK1a, Regulates Microtubule Dynamics and Dendrite Morphogenesis. Neuron, 90, 551-63 (2016).
Ori-McKenney KM, Jan LY, Jan YN. Golgi outposts shape dendrite morphology by functioning as sites of acentrosomal microtubule nucleation in neurons. Neuron, 76, 921-30 (2012).
- Preview: “Neuronal Morphogenesis: Golgi Outposts, Acentrosomal Microtubule Nucleation, and Dendritic Branching.” Lewis TL and Polleux F. Neuron, 76, 862-4 (2012).
- Editor’s Choice in Neuroscience: “Branching Out: Satellites of the Golgi apparatus generate microtubules used to grow outer dendrite branches in Drosophila neurons.” Cossins D. The Scientist, 52 (2013).
- F1000 Review
Harms M, Ori-McKenney KM, Scoto M, Tuck E, Bell S, Ma D, Masi S, Allred P, Al-Lozi, M, Reilly M, Miller L, Jani-Acsadi A, Shy M, Pestronk A, Muntoni F, Vallee RB, Baloh R. Mutations in the tail domain of cytoplasmic dynein (DYNC1H1) cause motor neuron disease in humans. Neurology, 78, 1-7 (2012).
Ori-McKenney KM*, Xu, J*, Gross SP, Vallee RB. A neurodegenerative mutation reveals novel features of cytoplasmic dynein motor regulation. Nature Cell Biology, 12, 1228-34 (2010). (*Co-first authors)
- News and Views: “Dynein at Odd Angles?” Hendricks AG, Lazarus JE, Holzbaur ELF, Nature Cell Biology, 12, 1126 (2010).