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Neurology and Neuroscience
855 N. Wolfe Street
Rangos 248, 2nd Floor
Baltimore, MD 21205
Intracellular trafficking in neuromuscular degenerative diseases.
Motor neurons are some of the largest cells in the human body, with axon lengths up to a meter long. This large size of motor neurons and muscle cells makes them particularly vulnerable to disruptions of intracellular trafficking with aging, leading to progressive weakness, muscle atrophy, and paralysis in diseases such as Amyotrophic Lateral Sclerosis (ALS), Charcot-Marie-Tooth Disease (CMT), and Inclusion Body Myositis (IBM). Our lab uses Drosophila, cell culture, and mouse models of neurodegenerative diseases to understand how processes including nucleocytoplasmic transport, RNA metabolism, protein translation, autophagy, and axonal transport are altered, and how these changes lead to age-dependent degeneration.
1. Zhang K, Daigle JG, Cunningham KM, Coyne AM, Ruan K, Grima JC, Bowen KE, Wadhwa H, Yang P, Rigo F, Taylor JP, Gitler AD, Rothstein JD*, Lloyd TE*. (2018) Stress granule formation disrupts nucleocytoplasmic transport. Cell. 173(4):958-971.
2. Vogler TO, Wheeler JR*, Nguyen ED, Hughes MP, Britson KA, Lester E, Rao B, Betta ND, Whitney ON, Ewachiw TE, Gomes E, Shorter J, Lloyd TE, Eisenberg DS, Taylor JP, Johnson AM, Olwin BB*, Parker R*. (2018) Amyloid-like TDP-43 myo-granules associate with 1 sarcomeric RNAs during skeletal muscle formation. Nature. 2018 563:508-513.
3. Zhang K, Coyne AN, Lloyd TE. (2018) Drosophila models of amyotrophic lateral sclerosis with defects in RNA metabolism. Brain Research. 1693:109-120.
4. Grima JC, Daigle JG, Arbez N, Cunningham KC, Zhang K, Ochaba J, Geater C, Morozko E, Glatzer JC, Pham JT, Ahmed I, Peng Q, Wadhwa H, Pletnikova Ol, Troncoso JC, Duan W, Matunis MJ, Ranum LP, Thompson LM, Lloyd TE, Ross CA, Rothstein JD. (2017) Mutant Huntingtin Disrupts the Nuclear Pore Complex. Neuron 94:93-107.
5. Zhang K#, Donnelly CJ#, Haeusler AR, Grima JC, Machamer JB, Steinwald P, Daley EL, Miller SJ, Cunningham KM, Vidensky S, Gupta S, Thomas MA, Hong I, Chiu SL, Huganir RL, Ostrow LW, Matunis MJ, Wang J, Sattler R, Lloyd TE*, Rothstein JD* (2015) The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature.525:56-61.
6. Machamer JB, Collins SE, Lloyd TE*. (2014) The ALS gene FUS regulates synaptic transmission at the Drosophila neuromuscular junction. Human Molecular Genetics. 23:3810-22.
7. Wong MY, Zhou C, Shakiryanova D, Lloyd TE, Deitcher DL, Levitan ES. (2012) Neuropeptide delivery to synapses by long-range vesicle circulation and sporadic capture. Cell. 148:1029-38.
8. Lloyd TE*, Machamer J, O'Hara K, Kim JH, Collins SE, Wong MY, Sahin B, Imlach W, Yang Y, Levitan ES, McCabe BD, Kolodkin AL*. (2012) The p150(Glued) CAP-Gly domain regulates initiation of retrograde transport at synaptic termini. Neuron 74:344-60.