Scientist, Vollum Institute
After earning his B.S. in Neuroscience from Allegheny College in 2001, Wright received his Ph.D. in Neurobiology from The University of North Carolina, Chapel Hill in 2006. He did his postdoctoral training at Johns Hopkins Medical Institute. In 2013 Wright joined the Vollum Institute as an assistant scientist and was promoted to scientist in 2020.
Summary of current research
Our ability to perceive of the world around us begins with primary sensory circuits. The neurons within these circuits have an astonishing level of diversity in their molecular properties, morphology and physiological function. Our group uses both the mouse dorsal root ganglia and retina as model systems to investigate how neurons are organized into functional circuits during development. In the somatosensory system, the dorsal root ganglia (DRG) contains at least 18 distinct primary somatosensory neuron subtypes convey information from the periphery to the central nervous system. DRG sensory neurons have a peripheral axon that forms specialized endings within the skin and an axon that synapses onto interneurons within the dorsal spinal cord. Of particular interest to the lab are the low threshold mechanoreceptors (LTMRs), which convey our sense of touch. Each LTMR subtype has a stereotyped morphology, connectivity pattern, and response properties that directly relate to the type of stimulus it conveys. In the mammalian visual system, the retina contains more than 100 distinct neuronal subtypes, each playing a specific role in the processing of visual information. The majority of this processing occurs within the inner plexiform layer of the retina, where the synaptic connections between 15 types of bipolar cells (BCs), >35 types of retinal ganglion cells (RGCs), and >35 types of amacrine cells (ACs) are all formed and precisely organized.
To investigate how somatosensory and retinal circuits develop, we utilize molecular–genetic approaches to answer the following questions:
- How are peripheral receptive fields and central projections of LTMRs established and organized during development?
- What are the molecular pathways that organize the axons and dendrites of >85 different retinal neurons within a space that is less than 60 microns wide?
- Using genetic approaches, how can we identify and manipulate individual neuron subtypes to understand their function?
- How are the development and function of somatosensory and retinal circuits affected in neurodevelopmental disorders?
Kerstein PC, Leffler J, Sivyer B, Taylor WR, Wright KM. (2020) Gbx2 identifies two amacrine cell subtypes with distinct molecular, morphological, and physiological properties. Cell Reports 33:108382.
Lindenmaier LB, Parmentier N, Guo C, Tissir F, Wright KM. (2019) Dystroglycan is a scaffold for extracellular axon guidance decisions. eLife 8. pii:e42143.
Clements R, Wright KM. (2018) Retinal ganglion cell axon sorting at the optic chiasm requires dystroglycan. Dev. Biol. 442:210-219.
Clements R, Turk R, Campbell KP, Wright KM. (2017) Dystroglycan maintains inner limiting membrane integrity to coordinate retinal development. J. Neurosci. 37:8559-8574.
Willer T, Inamori KI, Venzke D, Harvey C, Morgensen G, Hara Y, Beltrán Valero de Bernabé D, Yu L, Wright KM, Campbell KP. (2014) The glucuronyltransferase B4GAT1 is required for initiation of LARGE-mediated α-dystroglycan functional glycosylation. eLife 3:e03941.
Wright KM, Lyon K, Leung H, Leahy DJ, Ma L, Ginty DD (2012) Dystroglycan organizes axon guidance cue localization and axonal pathfinding. Neuron 76:931-944.
Charoy C, Nawabi H, Reynaud F, Derrington E, Bozon M, Wright K, Falk J, Helmbacher F, Kindbeiter K, Castellani V. (2012) GDNF activates midline repulsion by Semaphorin3B via NCAM during commissural axon guidance. Neuron 75:1051-1066.
Merte J, Jensen D, Wright K, Sarsfield S, Wang Y, Schekman R, Ginty DD. (2009) Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure. Nature Cell Biol. 12:41-46.
Johnson CE, Huang YY, Parrish AB, Smith MI, Vaughn AE, Zhang Q, Wright KM, Van Dyke T, Wechsler-Reya RJ, Kornbluth S, Deshmukh M. (2007) Differential Apaf-1 levels allow cytochrome c to induce apoptosis in brain tumors but not in normal neural tissues. Proc. Natl. Acad. Sci. USA 104:20820-20825.
Wright KM, Smith MI, Farrag L, Deshmukh M. (2007) Chromatin modification of Apaf-1 restricts the apoptotic pathway in mature neurons. J. Cell Biol. 179:825-832.
Wright KM, Vaughn AE, Deshmukh M. (2007) Apoptosome dependent caspase-3 activation pathway is non-redundant and necessary for apoptosis in sympathetic neurons. Cell Death Differ. 14:625-633.
Wright KM, Deshmukh M. (2006) Restricting apoptosis for postmitotitc cell survival and its relevance to cancer. Cell Cycle 5:1616-1620.
Schafer ZT, Parrish AB, Wright KM, Margolis SS, Marks JR, Deshmukh M, Kornbluth S. (2006) Enhanced sensitivity to cytochrome c induced apoptosis mediated by PHAPI in breast cancer cells. Cancer Research 66:2210-2218.
Wright KM, Linhoff MW, Potts PR, Deshmukh M. (2004) Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis. J. Cell Biol. 167:303-313.