Academic Appointments
- Associate Professor of Neurology
- Associate Professor of Pathology & Cell Biology
Email: ay46@cumc.columbia.edu
The overriding theme of our research is to examine the molecular mechanism of protein trafficking events that modulate neural function and neurodegeneration. Our studies have focused on two forms of protein trafficking, one that mediates elimination of abnormal cellular proteins and a second that modulates the function of normal cellular proteins. In the former case we 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. In the latter case, our goal is to identify how cholesterol rich membrane microdomains modulate the function of membrane proteins such as neurotransmitter transporters, and how this impacts neurotransmission.
The strategy underlying our work begins with fundamental biochemical and cell biological approaches to identify the key molecular regulators of a protein trafficking event. Our goal is to apply these findings to the developing and adult brain using mouse genetics, to determine if modulating our pathway of interest can modify disease states. Transitioning our cell-based findings into the correct environmental context is critical; the highly specialized nature of neural cell types can lead to unexpected adaptations of a cellular pathway. Moreover, the cellular needs of an embryonic brain may be quite distinct from an aging one. These hypotheses driven studies in mice then inform us how we can further interpret our cell based work in the context of neural function, and importantly, how we can apply our findings to disease.
Departments and Divisions
- Department of Neurology
Division of Movement Disorders - Department of Pathology & Cell Biology
Education and Training
- BS, 1994 Material Science and Engineering, Massachusetts Institute of Technology
- PhD, 2002 Columbia University, New York, NY
Links
Lab Locations
William Black Building
650 West 168th Street
3rd Fl, Room 301B
New York, NY 10032- Phone:
- (212) 305-9206
- Email:
- ay46@cumc.columbia.edu
Research Interests
- Disease
- Neural Degeneration and Repair
- Protein trafficking
- Roles of macroautophagy in the healthy and diseased CNS
NIH Grants
MODULATING SELECTIVE AUTOPHAGY TO MODIFY HUNTINGTON S DISEASE (Federal Gov)
Apr 15 2019 - Mar 31 2024
SELECTIVE AUTOPHAGY IN PARKINSON S DISEASE (Federal Gov)
Jul 1 2018 - Mar 31 2023
AUTOPHAGY AND NEURODEGENERATION (Federal Gov)
Apr 1 2015 - Mar 31 2021
ABERRATIONS IN AUTOPHAGY IN THE HUMAN BRAIN OF HUNTINGTON S DISEASE: A POST-MORTEM STUDY WITH CORRELATION TO MURINE MODELS (Private)
Dec 3 2018 - Dec 2 2020
GENERATION OF STRIATAL NEURONS FROM HD PATIENT-DERIVED FIBROBLASTS: A FEASIBILITY STUDY WITH DIRECT CORRELATION TO HUMAN NEUROPATHOLOGY (Private)
Sep 1 2019 - Aug 31 2020
AUTOPHAGY AND NEURODEGENERATION (Federal Gov)
Apr 1 2015 - Mar 31 2020
IDENTIFICATION OF THE INITIAL CELLULAR SITE OF ACTION OF A-SYNUCLEIN IN THE PATHOGENESIS OF PARKINSON S DISEASE IN VIVO. (Federal Gov)
Jul 1 2017 - Jun 30 2019
SELECTIVE AUTOPHAGY AND ALS (Private)
Jan 1 2017 - Dec 31 2018
SERVICE AGREEMENT: NPT088 EUREKA IGG1 NEGATIVE CONTROL (CATALOGUE # ET901) PBS (P&S Industry Clinical Trial)
Aug 28 2013 - Aug 28 2018
ALFY-MEDIATED DEGRADATION AND HD (Private)
Jan 20 2017 - Jan 19 2018
CELLULAR MECHANISMS CONTROLLING WHITE MATTER CONNECTIVITY: MAKING SENSE OF A GENETIC RISK FACTOR FOR AUTISM AND SCHIZOPHERNIA (Private)
Jan 15 2016 - Jan 14 2018
PARKINSON S DISEASE FOUNDATION (PDF) RESEARCH CENTER GRANT (Private)
Jul 1 2016 - Jun 30 2017
ALFY-MEDIATED DEGRADATION AND HD (Private)
Mar 1 2016 - Feb 28 2017
PARKINSONS DISEASE FOUNDATION RESEARCH CENTER GRANT (Private)
Jul 1 2000 - Jun 30 2016
MODULATING AGGREPHAGY TO MODIFY HUNTINGTON S DISEASE (Federal Gov)
Apr 1 2012 - Mar 31 2016
ALFY-MEDIATED SELECTIVE MACROAUTOPHAGY AND THE PATHOGENESIS OF HUNTINGTON S DISEASE (Federal Gov)
Sep 1 2013 - Aug 31 2015
ALFY-MEDIATED SELECTIVE MACROAUTOPHAGY AND THE PATHOGENESIS OF HUNTINGTON S DISEASE (Federal Gov)
Sep 1 2013 - Aug 31 2015
STRUCTURE AND FUNCTION OF NEUROTRANSMITTER TRANSPORTERS (Federal Gov)
Mar 1 2011 - Feb 28 2015
PARKINSONS DISEASE FOUNDATION RESEARCH CENTER GRANT (Private)
Jul 1 2000 - Jun 30 2014
PARKINSON S DISEASE FOUNDATION RESEARCH CENTE (Private)
Jul 1 2000 - Jun 30 2014
PARKINSONS DISEASE FOUNDATION (PDF) RESEARCH CENTER GRANT 2012-2013 (Private)
Jul 1 2009 - Jun 30 2013
STRUCTURE AND FUNCTION OF NEUROTRANSMITTER TRANSPORTERS (Federal Gov)
Mar 1 2011 - Feb 28 2013
CAN THE INHIBITION OF FARNESYLATION POSITIVELY MODIFY THE CL EARANCE OF EXPANDED POLYGLUTAMINE INCLUSIONS? (Private)
Oct 1 2010 - Dec 31 2011
PROTEIN TRAFFICKING IN NEURODEGENERATIVE DISEASES (Federal Gov)
Sep 30 2009 - Aug 31 2011
Publications
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) eLife. Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain. 5: e14810
Eenjes, E., Dragich, J.M., Kampinga, H.H. and Yamamoto, A. Distinguishing aggregate formation versus aggregate clearance using cell based assays. (2016) J Cell Sci 129(6): 1260-1270.
Yamamoto, A. and Yue, Z.-Y. (2014) Autophagy and its Normal and Pathogenic States in the brain. Ann Rev Neurosci. 37:55-78.
Nath, S., Puente, P., Dancourt, J., Fong, W., Nag, S., Yamamoto, A., Antonny, B., Melia, T.J. (2014) Lipidation of the autophagy protein LC3 is a membrane curvature-dependent process. Nat Cell Biol. 16(5): 415-424. PMC24747438
Cremona, M.L., Matties, H.J.G., Bowton, E., Speed, N., Lute, B.J., Pau, K., Anderson, M.A., Sen, N., Doughty, S.E., Rothman, J.E., Galli, A., Javitch, J.A. and Yamamoto, A. (2011) Flotillin-1 is essential for dopamine transporter endocytosis and reverse-transport of dopamine. Nat. Neurosci. 14:469-477.
Yamamoto, A. and Simonsen, A. (2011) The elimination of accumulated and aggregated proteins: A role for aggrephagy in neurodegeneration. Neurobiol. Dis.43:17-28
Filimonenko, M., Isakson, P., Finley, K.D., Anderson, M., Melia, Jr., Jeong, H., T.J., Bartlett, B.J., Myers, K.M., Birkeland, H.C.G., Lamark, T., Krainc, D., Brech, A., Stenmark, H., Simonsen, A. and Yamamoto, A. (2010) The selective macroautophagic degradation of aggregated proteins requires the PI3-P binding protein, Alfy. Molecular Cell 2: 265-279