Associate Professor of Neurology,
Pathology & Cell Biology
Columbia University Irving Medical Center, New York
Ai Yamamoto’s group is interested in the molecular mechanism of protein trafficking events that modulate neural function and neurodegeneration, focusing on forms of protein trafficking. They seek to understand how protein cargoes implicated in degenerative diseases are selected for degradation by the macroautophagy pathway, and are currently exploring how selective and basal macroautophagic processes are regulated in the healthy and diseased brain. Further, they aim at identifying how cholesterol rich membrane microdomains modulate the function of membrane proteins such as neurotransmitter transporters, and how this impacts neurotransmission. Beginning with fundamental biochemical and cell biological approaches to identify the key molecular regulators of a protein trafficking event, their goal is to apply these findings to the developing and adult brain using mouse genetics, to determine if modulating the pathway of interest can modify disease states.
Huntington’s disease pathogenesis is modified in vivo by selective macroautophagy.
Neuron (in press)
Fox, L.M., Kim, K., Johnson, C.W., Victor, .B., Croce, K.R., Eenjes, E., Bosco, J.R., Randolph, L.K., Dragatsis, I., Dragich, J.M., Yoo, A.S. and Yamamoto, A. (2019)
Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain.
eLife 5: e14810 doi: 10.7554/eLife.14810
Dragich, J.M., Kuwajima, T., Hirose-Ikeda, M., Yoon, M.S., Eenjes, E., Bosco, J.R., Fox, L.M., Lystad, A.H., Oo, T.F., Yarygina, O., Mita, T., Waguri, S., Ichimura, Y., Komatsu, M., Simonsen, A., Burke, R.E., Mason, C.A. and Yamamoto, A. (2016)
Distinguishing aggregate formation versus aggregate clearance using cell based assays.
Journal of Cell Science 129(6): 1260-1270 doi: 10.1242/jcs.179978
Eenjes, E., Dragich, J.M., Kampinga, H.H. and Yamamoto, A. (2016)
Lipidation of the LC3/GABARAP family of autophagy proteins relies on a membrane-curvature-sensing domain in Atg3
Nature Cell Biology 16(5): 415–424. doi: 10.1038/ncb2940
Nath, S., Puente, P., Dancourt, J., Fong, W., Nag, S., Yamamoto, A., Antonny, B., Melia, T.J. (2014)
A role for autophagy in Huntington's disease.
Neurobiology of Disease 122:16-22. doi: 0.1016/j.nbd.2018.08.010
Croce KR., Yamamoto A. (2019)
Autophagy and its Normal and Pathogenic States in the brain
Annual Review of Neuroscience37:55-78 doi: 10.1146/annurev-neuro-071013-014149
Yamamoto, A. and Yue, ZY. (2014)
The elimination of accumulated and aggregated proteins: a role for aggrephagy in neurodegeneration
Neurobiology of Disease 43(1):17-28. doi: 10.1016/j.nbd.2010.08.015
Yamamoto A., Simonsen A. (2011)