研究领域
Molecular Biology and Disease
Cell Signalling and Structure
What happens in our brains as we age? This is a critical question that drives the research of my laboratory at the University of Calgary since September 2005. The main goal of my research program is to understand the basic mechanisms governing brain aging and neurodegenerative disorders; the increased age being the main risk factor for neurodegeneration.
To tackle these two problems, we use a very basic molecular cell biology approach to study the neuronal cytoskeleton (the internal scaffolding that provides structure for the cell, as well as transports materials and sends signals to other parts of the cell) and its associated signaling proteins. Mutations or alterations in the neuronal cytoskeleton can lead to premature aging and neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. This work sometimes leads us to revisit the physiological functions of these molecules such as during neuronal development, maturation, plasticity and investigate their potential to promote repair (for further details, see Philosophy of Research).
近期论文
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Kurabayashi N, NguyenMD, & Sanada K. DYRK1A overexpression enhances STAT activity and astrogliogenesis in a mouse model of Down’s syndrome. EMBO Reports, pii: e201540374 (2015).
Shim SY, Castro-Perez I, Neumayer G, Wang J, Park SK, Sanada K & Nguyen MD. Phosphorylation of Targeting Protein for Xenopus kinesin-like protein 2 (TPX2) at threonine 72 in spindle assembly. Journal of Biological Chemistry, 290: 9122-34 (2015).
Parsons K, Yoshihiro Nakatani & Nguyen MD. p600 / UBR4 in the central nervous system. Cellular and Molecular Life Sciences, 72: 1149-60 (2015)
Neumayer G & Nguyen MD. TPX2 impacts acetylation of Histone H4 at lysine 16: Implications for DNA damage response. PLOS ONE, Nov 3;9(11):e110994. doi: 10.1371/journal.pone.0110994. eCollection (2014).
Belzil C, Asada N, Ishiguro K, Nakaya T, Parsons K, Pendolino V, Neumayer G, Mapelli M, Nakatani Y, Sanada S & Nguyen MD. p600 regulates spindle orientation in apical neural progenitors and contributes to neurogenesis in the developing neocortex. Biology Open 3:475-85 (2014).
Neumayer G, Belzil C, Gruss O & Nguyen MD. TPX2: Of spindle assembly, DNA damage response and cancer. Cellular and Molecular Life Sciences, 71:3027-47 (2014). Cover of the July issue.
Tamai SI, Kurabayashi N, NguyenMD, AbeT, InoueM, Fukada Y & Sanada K. Neuroprotective role of basic leucine transcription factor Nfil3 in models of amyotrophic lateral sclerosis. Journal of Biological Chemistry, 289:1629-38 (2013).
Kurabayashi N, NguyenMD, & Sanada K. GPRC5B, a G protein-coupled receptor, contributes to neurogenesis in the developing neocortex. Development, 140: 4335-46 (2013).
Belzil C, Neumayer G, Vassilev AP, Yap KL, Konishi H, Rivest S, Sanada S, Ikura M, Nakatani Y & Nguyen MD. A Ca2+-dependent mechanism of neuronal survival mediated by the microtubule- associated protein p600. Journal of Biological Chemistry, 288: 24452-64 (2013).
NakayaT, IshiguroKI, BronsonRT, MizunoSI, HerlitzAM, Yu Q, Geng Y, BelzilC, NguyenMD, AkashiK, SicinskiP & Nakatani Y. p600 Plays Essential Roles in Fetal Development. PLOS ONE, 8(6):e66269 (2013).
Tasaki T, Kim ST, Zakrzewska A, Lee BE, Kang MJ, Yoo YD, Cha-Molstad HJ, Hwang J, Soung NK, Sung KS, Kim SH, NguyenMD, Sun M, Yi EC, BY Kim & Kwon YT. UBR4, a N-recognin of the the N-end rule pathway, and its role in yolk sac vascular development and autophagy. Proc Natl Acad Sci USA, 110: 3800-5 (2013).
Neumayer G, Helfricht A, Shim S, Le Thi H, Lundin C, Belzil C, Chansard M, Gruss O, Lees Miller SP, van Attikum H, Helleday T & Nguyen MD. Targeting Protein for Xenopus kinesin-like protein 2 (TPX2) regulates gamma-H2AX levels upon ionizing radiation. Journal of Biological Chemistry, 287: 42206-42222 (2012). featured at globalmedicaldiscovery.com/key-scientific-articles/targeting-protein-for-xenopus-kinesin-like-protein-2-tpx2-regulates-gamma-h2ax-levels-upon-ionizing-radiation/
ChansardM, HongJ-H, ParkY-U, ParkSK & Nguyen MD. Ndel1, Nudel (noodle): Flexible in the Cell? Cytoskeleton, 68:540-54 (2011).
ChansardM, WangJ, TranHC, NeumayerG, ShimSY, ParkYU, BelzilC, Le ThiH, ParkSK & NguyenMD. The cytoskeletal protein Ndel1 regulates Dyn2 GTPase activity. PLOS ONE, 6:e14583 (2011).
Park YU, Lee H, Jeong J , Young Mun J, Kim JH, Lee JS, Nguyen MD, Han SS, Suh PG & Park SK. Disrupted-in-schizophrenia 1 (DISC1) plays essential roles in mitochondria in collaboration with Mitofilin. Proc Natl Acad Sci USA 107: 17785-90 (2010).
Toth C*, Shim S*, Wang J, Jiang Y, Neumayer G, Belzil C, Liu WQ, Martinez J, Zochodne DW & Nguyen MD. Ndel1 promotes axon regeneration via intermediate filaments. PLOS ONE 3:e2014 (2008).*These authors contributed equally to this work
Shim S, Wang J, Asada N, Neumayer G, Tran HC, Ishiguro K, Sanada K, Nakatani Y & Nguyen MD. P600 is a Microtubule / Endoplasmic Reticulum - Associated Protein in CNS Neurons. Journal of Neuroscience 28: 3604-3614 (2008).
Shim S, Samuels BA*, Wang J*, Neumayer G, Belzil C, Ayala R, Shi Y, Shi Y, Tsai LH & Nguyen MD. Ndel1 controls the Dynein-mediated transport of Vimentin during neurite outgrowth. Journal of Biological Chemistry 283:12232-4 (2008). *These authors contributed equally to this work
Kim D*, Nguyen MD*, Fischer A, Sanabenesi F, Dobbins M, Rodgers JT, Dellale I, Sui G, Baur JA, Armour S, Puigserver P, Sinclair DA & Tsai LH. SIRT1 deacetylase protects against neurodegeneration in mouse models of Alzheimer’s disease and Amyotrophic Lateral Sclerosis. EMBO Journal. 26: 3169-3179 (2007).*These authors contributed equally to this work. One the 10 most-read EMBO papers online in July 2007
Park SK, Nguyen MD*, Fisher A*, Luke MP, Affar EB, Dieffenback P, Tseng HC, Shi Y & Tsai LH. Prostate apoptosis response 4 links dopamine signaling and depression. Cell 122: 275-287 (2005) *These authors contributed equally to this work Previewed in Cell, p153-155 (2005), Cover of the July Issue. Commented in Neuron, Vol 47, 335-338 (2005). Science STKE Editor choice, 295: tw 277. Commented in Psychiatry Dispatches in Primary Psychiatry, 12: 12-23