The Marsh-Armstrong laboratory studies molecular mechanisms involved in gene regulation, development and disease of the central nervous system, focusing principally on the retina. Most studies are carried out in frogs in order to perform experimental approaches that rely on high throughput transgenesis. Currently, there are three major areas of interest:
- Metamorphic remodeling of the nervous system. Studying metamorphic programs has enabled the lab to identify molecular pathways that are general to vertebrate neural development by virtue of their regulation by thyroid hormone in frogs. In one particular lineage, the generation of ipsilaterally projecting retinal ganglion cells, they are studying how these cells are generated from neural progenitor cells as well as the novel axon guidance mechanism that they use.
- Photoreceptor degeneration. The lab has developed several frog models of photoreceptor degeneration that are similar to mammalian models but that enable novel experimental approaches. These models are used to explore the nature of rhodopsin mutations that cause retinitis pigmentosa and the molecular mechanisms by which rod photoreceptors degenerate. The lab is also using some of these lines in High Throughput Screening (HTS) assays looking for chemicals that prevent or slow photoreceptor degenerations.
- Glaucoma. The Marsh-Armstrong lab is part of a collaborative project, “Catalyst for a Cure,” that is dedicated to understanding the molecular mechanisms underlying the loss of retinal ganglion cells in glaucoma. Most of these studies involve a mouse model of glaucoma, the DBA/2J mouse, and involve interventions that aim to slow disease progression.
Lab Website: Nicholas Marsh-Armstrong Lab
Welsbie DS, Yang Z, Ge Y, Mitchell KL, Zhou X, Martin SE, Berlinicke CA, Hackler L Jr, Fuller J, Fu J, Cao LH, Han B, Auld D, Xue T, Hirai S, Germain L, Simard-Bisson C, Blouin R, Nguyen JV, Davis CH, Enke RA, Boye SL, Merbs SL, Marsh-Armstrong N, Hauswirth WW, DiAntonio A, Nickells RW, Inglese J, Hanes J, Yau KW, Quigley HA, Zack DJ. "Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death." Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4045-50. doi: 10.1073/pnas.1211284110. Epub 2013 Feb 19. PubMed PMID: 23431148.
Watson FL, Mills EA, Wang X, Guo C, Chen DF, Marsh-Armstrong N. "Cell type-specific translational profiling in the Xenopus laevis retina." Dev. Dyn. 2012 241:1960-72. PMID: 23074098.
Peters OM, Millership S, Shelkovnikova TA, Soto I, Keeling L, Hann A, Marsh-Armstrong N, Buchman VL, Ninkina N. "Selective pattern of motor system damage in gamma-synuclein transgenic mice mirrors the respective pathology in amyotrophic lateral sclerosis." Neurobiol Dis. 2012 Oct;48(1):124-31. doi: 10.1016/j.nbd.2012.06.016. Epub 2012 Jun 30. PubMed PMID: 22750530.
Nguyen JV, Soto I, Kim KY, Bushong EA, Oglesby E, Valiente-Soriana FJ, Yang Z, Davis CH, Bedont JL, Son JL, Wei JO, Buchman VL, Zack DJ, Vidal-Sanz M, Ellisman MH, Marsh-Armstrong N. "Myelination transition zone astrocytes are constitutively phagocytic and have synuclein dependent reactivity in glaucoma." Proc Natl Acad Sci U S A. 2011 108:1176-1181 PMID: 21199938.
Soto I, Pease ME, Son JL, Shi X, Quigley HA, Marsh-Armstrong N. "Retinal ganglion cell loss in a rat ocular hypertension model is sectorial and involves early optic nerve axon loss." Inv. Ophth. Vis. Sci. 2011 52:434-41 PMID: 20811062
Son JL, Soto I, Oglesby E, Lopez-Roca T, Pease ME, Quigley HA, Marsh-Armstrong N. (2010) Glaucomatous optic nerve injury involves early astrocyte reactivity and late oligodendrocyte loss. Glia. 58:780-9.PMID: 20091782