Bio

Bio

I am a passionate scientist with expertise in basic and translational research related to ageing, cancer, genomic instability, DNA damage response (HDR & NHEJ), genome editing (CRISPR), regenerative medicine (iPSCs), cellular identity (reprogramming), and proteomics (interactions, biomarkers, target identification). My extensive experience is reflected by 10 peer reviewed publications. I possess excellent communication and technical writing skills (English/German), as evidenced by collaborations with world renowned institutions and >$460,000 won from scholarships, grants & awards. Recent highlights: Postdoctoral Young Investigator Award from Stanford University for scientific merit, commitment & leadership; ?Played a big part? in securing a CRISPR-based $5.1Mio grant for regenerative medicine at Stanford University; Poster prize (out of 77 entries) at the Department of Pathology, Stanford University 2019 research day.

Honors & Awards

  • BSc Scholarship for Academic Achievement, University of Salzburg, Austria
  • MSc awarded with highest distinction, University of Salzburg, Austria
  • Achievers in Medical Science Graduate Recruitment Scholarship, Anonymous Donor via the University of Calgary, Canada
  • Faculty of Graduate Studies PhD Scholarship, University of Calgary, Canada
  • Travel Award for Scientific Symposium: DNA Damage-From Causes to Cures, The Biochemical Society, London, UK
  • DOC-PhD Scholarship, Austrian Academy of Sciences, Vienna, Austria
  • 4x Achievers in Medical Science Research Excellence Award, Anonymous Donor via the University of Calgary, Canada
  • Travel Award for Gordon Research Conference: Mammalian DNA repair, Gordon Research Conferences, Ventura, USA
  • Award for best poster at the 2009 HBI Conference, Hotchkiss Brain Institute, University of Calgary, Canada
  • 2x Graduate Student Award, Department of Biochemistry and Molecular Biology, University of Calgary, Canada
  • Award for best poster at the 2010 BMB Departmental Retreat, Department of Biochemistry and Molecular Biology, University of Calgary, Canada
  • ACF Graduate Studentship, Alberta Cancer Foundation, Calgary/Edmonton, Canada

Projects

  • Revealing the protein interface between Staphylococcus aureus and Human, University of Salzburg

    Location

    Austria

  • Defining a role for TPX2 in the nucleus: Regulation of the DNA damage response, University of Calgary

    Location

    Canada

  • Epigenetic-based mechanisms of DNA damage response, University of Calgary

    Location

    Canada

  • Investigating the function of the SIRT1 deacetylase, University of Calgary

    Location

    Canada

Contact

Links

Professional

Professional Affiliations and Activities

  • Member, ASCINA-Austrian scientists in North America (2014 - Present)

Publications

All Publications

  • Scalable production of CRISPR-corrected autologous iPSC derived skin grafts to treat epidermolysis bullosa Torkelson, J. L., Hansen, C., Jackow, J., Guo, Z., Hui-Zhen, H., Hayashi, R., Sallee, B., McCarthy, K., Neumayer, G., McGrath, P. S., Bilousova, G., Kogut, I., Roop, D., Christiano, A., Wernig, M., Oro, A. ELSEVIER SCIENCE INC. 2019: S179

    View details for Web of Science ID 000465561505177

  • Phosphorylation of Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) at Threonine 72 in Spindle Assembly JOURNAL OF BIOLOGICAL CHEMISTRY Shim, S. Y., Perez de Castro, I., Neumayer, G., Wang, J., Park, S. K., Sanada, K., Minh Dang Nguyen, M. D. 2015; 290 (14): 9122-9134

    Abstract

    The human ortholog of the targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a cytoskeletal protein that plays a major role in spindle assembly and is required for mitosis. During spindle morphogenesis, TPX2 cooperates with Aurora A kinase and Eg5 kinesin to regulate microtubule organization. TPX2 displays over 40 putative phosphorylation sites identified from various high-throughput proteomic screenings. In this study, we characterize the phosphorylation of threonine 72 (Thr(72)) in human TPX2, a residue highly conserved across species. We find that Cdk1/2 phosphorylate TPX2 in vitro and in vivo. Using homemade antibodies specific for TPX2 phosphorylated at Thr(72), we show that this phosphorylation is cell cycle-dependent and peaks at M phase. Endogenous TPX2 phosphorylated at Thr(72) does not associate with the mitotic spindle. Furthermore, ectopic GFP-TPX2 T72A preferentially concentrates on the spindle, whereas GFP-TPX2 WT distributes to both spindle and cytosol. The T72A mutant also increases the proportion of cells with multipolar spindles phenotype. This effect is associated with increased Aurora A activity and abnormally elongated spindles, indicative of higher Eg5 activity. In summary, we propose that phosphorylation of Thr(72) regulates TPX2 localization and impacts spindle assembly via Aurora A and Eg5.

    View details for DOI 10.1074/jbc.M114.591545

    View details for Web of Science ID 000352207100035

    View details for PubMedID 25688093

    View details for PubMedCentralID PMC4423697

  • TPX2 Impacts Acetylation of Histone H4 at Lysine 16: Implications for DNA Damage Response PLOS ONE Neumayer, G., Minh Dang Nguyen, M. D. 2014; 9 (11)

    Abstract

    During interphase, the spindle assembly factor TPX2 is compartmentalized in the nucleus where its roles remain largely uncharacterized. Recently, we found that TPX2 regulates the levels of serine 139-phosphoryated H2AX (?-H2AX) at chromosomal breaks induced by ionizing radiation. Here, we report that TPX2 readily associates with the chromatin in the absence of ionizing radiation. Overexpression of TPX2 alters the DAPI staining pattern of interphase cells and depletion of TPX2 constitutively decreases the levels of histone H4 acetylated at lysine16 (H4K16ac) during G1-phase. Upon ionizing irradiation, this constitutive TPX2 depletion-dependent decrease in H4K16ac levels correlates with increased levels of ?-H2AX. The inversely correlated levels of H4K16ac and ?-H2AX can also be modified by altering the levels of SIRT1, herein identified as a novel protein complex partner of TPX2. Furthermore, we find that TPX2 depletion also interferes with formation of 53BP1 ionizing radiation-induced foci, known to depend on ?-H2AX and the acetylation status of H4K16. In brief, our study is the first indication of a constitutive control of TPX2 on H4K16ac levels, with potential implications for DNA damage response.

    View details for DOI 10.1371/journal.pone.0110994

    View details for Web of Science ID 000345558100041

    View details for PubMedID 25365214

    View details for PubMedCentralID PMC4217740

  • TPX2: of spindle assembly, DNA damage response, and cancer CELLULAR AND MOLECULAR LIFE SCIENCES Neumayer, G., Belzil, C., Gruss, O. J., Minh Dang Nguyen, M. D. 2014; 71 (16): 3027-3047

    Abstract

    For more than 15 years, TPX2 has been studied as a factor critical for mitosis and spindle assembly. These functions of TPX2 are attributed to its Ran-regulated microtubule-associated protein properties and to its control of the Aurora A kinase. Overexpressed in cancers, TPX2 is being established as marker for the diagnosis and prognosis of malignancies. During interphase, TPX2 resides preferentially in the nucleus where its function had remained elusive until recently. The latest finding that TPX2 plays a role in amplification of the DNA damage response, combined with the characterization of TPX2 knockout mice, open new perspectives to understand the biology of this protein. This review provides an historic overview of the discovery of TPX2 and summarizes its cytoskeletal and signaling roles with relevance to cancer therapies. Finally, the review aims to reconcile discrepancies between the experimental and pathological effects of TPX2 overexpression and advances new roles for compartmentalized TPX2.

    View details for DOI 10.1007/s00018-014-1582-7

    View details for Web of Science ID 000339718900003

    View details for PubMedID 24556998

  • p600 regulates spindle orientation in apical neural progenitors and contributes to neurogenesis in the developing neocortex BIOLOGY OPEN Belzil, C., Asada, N., Ishiguro, K., Nakaya, T., Parsons, K., Pendolino, V., Neumayer, G., Mapelli, M., Nakatani, Y., Sanada, K., Minh Dang Nguyen, M. D. 2014; 3 (6): 475-485

    Abstract

    Apical neural progenitors (aNPs) drive neurogenesis by means of a program consisting of self-proliferative and neurogenic divisions. The balance between these two manners of division sustains the pool of apical progenitors into late neurogenesis, thereby ensuring their availability to populate the brain with terminal cell types. Using knockout and in utero electroporation mouse models, we report a key role for the microtubule-associated protein 600 (p600) in the regulation of spindle orientation in aNPs, a cellular event that has been associated with cell fate and neurogenesis. We find that p600 interacts directly with the neurogenic protein Ndel1 and that aNPs knockout for p600, depleted of p600 by shRNA or expressing a Ndel1-binding p600 fragment all display randomized spindle orientation. Depletion of p600 by shRNA or expression of the Ndel1-binding p600 fragment also results in a decreased number of Pax6-positive aNPs and an increased number of Tbr2-positive basal progenitors destined to become neurons. These Pax6-positive aNPs display a tilted mitotic spindle. In mice wherein p600 is ablated in progenitors, the production of neurons is significantly impaired and this defect is associated with microcephaly. We propose a working model in which p600 controls spindle orientation in aNPs and discuss its implication for neurogenesis.

    View details for DOI 10.1242/bio.20147807

    View details for Web of Science ID 000348069200007

    View details for PubMedID 24812355

  • A Ca2+-dependent Mechanism of Neuronal Survival Mediated by the Microtubule-associated Protein p600 JOURNAL OF BIOLOGICAL CHEMISTRY Belzil, C., Neumayer, G., Vassilev, A. P., Yap, K. L., Konishi, H., Rivest, S., Sanada, K., Ikura, M., Nakatani, Y., Minh Dang Nguyen, M. D. 2013; 288 (34): 24452-24464

    Abstract

    In acute and chronic neurodegeneration, Ca(2+) mishandling and disruption of the cytoskeleton compromise neuronal integrity, yet abnormalities in the signaling roles of cytoskeletal proteins remain largely unexplored. We now report that the microtubule-associated protein p600 (also known as UBR4) promotes neuronal survival. Following depletion of p600, glutamate-induced Ca(2+) influx through NMDA receptors, but not AMPA receptors, initiates a degenerative process characterized by endoplasmic reticulum fragmentation and endoplasmic reticulum Ca(2+) release via inositol 1,4,5-trisphosphate receptors. Downstream of NMDA receptors, p600 associates with the calmodulinˇcalmodulin-dependent protein kinase II? complex. A direct and atypical p600/calmodulin interaction is required for neuronal survival. Thus, p600 counteracts specific Ca(2+)-induced death pathways through regulation of Ca(2+) homeostasis and signaling.

    View details for DOI 10.1074/jbc.M113.483107

    View details for Web of Science ID 000330612300015

    View details for PubMedID 23861403

    View details for PubMedCentralID PMC3750145

  • Targeting protein for xenopus kinesin-like protein 2 (TPX2) regulates ?-histone 2AX (?-H2AX) levels upon ionizing radiation. journal of biological chemistry Neumayer, G., Helfricht, A., Shim, S. Y., Le, H. T., Lundin, C., Belzil, C., Chansard, M., Yu, Y., Lees-Miller, S. P., Gruss, O. J., van Attikum, H., Helleday, T., Nguyen, M. D. 2012; 287 (50): 42206-42222

    Abstract

    The microtubule-associated protein targeting protein for Xenopus kinesin-like protein 2 (TPX2) plays a key role in spindle assembly and is required for mitosis in human cells. In interphase, TPX2 is actively imported into the nucleus to prevent its premature activity in microtubule organization. To date, no function has been assigned to nuclear TPX2. We now report that TPX2 plays a role in the cellular response to DNA double strand breaks induced by ionizing radiation. Loss of TPX2 leads to inordinately strong and transient accumulation of ionizing radiation-dependent Ser-139-phosphorylated Histone 2AX (?-H2AX) at G(0) and G(1) phases of the cell cycle. This is accompanied by the formation of increased numbers of high intensity ?-H2AX ionizing radiation-induced foci. Conversely, cells overexpressing TPX2 have reduced levels of ?-H2AX after ionizing radiation. Consistent with a role for TPX2 in the DNA damage response, we found that the protein accumulates at DNA double strand breaks and associates with the mediator of DNA damage checkpoint 1 (MDC1) and the ataxia telangiectasia mutated (ATM) kinase, both key regulators of ?-H2AX amplification. Pharmacologic inhibition or depletion of ATM or MDC1, but not of DNA-dependent protein kinase (DNA-PK), antagonizes the ?-H2AX phenotype caused by TPX2 depletion. Importantly, the regulation of ?-H2AX signals by TPX2 is not associated with apoptosis or the mitotic functions of TPX2. In sum, our study identifies a novel and the first nuclear function for TPX2 in the cellular responses to DNA damage.

    View details for DOI 10.1074/jbc.M112.385674

    View details for PubMedID 23045526

    View details for PubMedCentralID PMC3516765

  • Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) Regulates gamma-Histone 2AX (gamma-H2AX) Levels upon Ionizing Radiation JOURNAL OF BIOLOGICAL CHEMISTRY Neumayer, G., Helfricht, A., Shim, S. Y., Hoa Thi Le, H. T., Lundin, C., Belzil, C., Chansard, M., Yu, Y., Lees-Miller, S. P., Gruss, O. J., van Attikum, H., Helleday, T., Minh Dang Nguyen, M. D. 2012; 287 (50): 42206-42222

    View details for DOI 10.1074/jbc.M112.385674

    View details for Web of Science ID 000312103000057

  • The Cytoskeletal Protein Ndel1 Regulates Dynamin 2 GTPase Activity PLOS ONE Chansard, M., Wang, J., Hong Chi Tran, C. T., Neumayer, G., Shim, S. Y., Park, Y., Belzil, C., Hoa Thi Le, T. L., Park, S. K., Minh Dang Nguyen, D. N. 2011; 6 (1)

    Abstract

    Cytoskeleton dynamics, membranes trafficking and positioning are essential for the proper functioning of any mammalian cell. The identification of the molecules and mechanisms that allow these cellular processes to interface is vital for understanding cell behaviors. Ndel1, the mammalian homolog of the Aspergillus nidulans NudE, organizes the cytoskeleton and regulates molecular motors, thereby impacting on the positioning of membranes. Hypothetically, Ndel1 can act in concert with enzymes controlling membrane trafficking (vesicle-mediated transport) per se, but this idea has never been investigated. We now report that a pool of Ndel1 associates directly with Dynamin 2 (Dyn2), a large cytosolic GTPase involved in the trafficking of the AMPA receptor subunit GluR1. In vitro, Ndel1 enhances Dyn2 GTPase activity in its unassembled and assembled forms, without promoting oligomerization of the enzyme. In cells, gain and loss of function of Ndel1 recapitulate the effects of overexpression of Dyn2 and Dyn2 dominant negative with reduced GTPase activity on the intracellular localization of GluR1, respectively, without affecting the stability of microtubules. Together, these results indicate that Ndel1 regulates Dyn2 GTPase activity and impacts GluR1-containing membranes distribution in a manner reminiscent of Dyn2.

    View details for DOI 10.1371/journal.pone.0014583

    View details for Web of Science ID 000286661400002

    View details for PubMedID 21283621

    View details for PubMedCentralID PMC3026782

  • Ndel1 controls the dynein-mediated transport of vimentin during neurite outgrowth JOURNAL OF BIOLOGICAL CHEMISTRY Shim, S. Y., Samuels, B. A., Wang, J., Neumayer, G., Belzil, C., Ayala, R., Shi, Y., Shi, Y., Tsai, L., Nguyen, M. D. 2008; 283 (18): 12232-12240

    Abstract

    Ndel1, the mammalian homologue of the Aspergillus nidulans NudE, is emergently viewed as an integrator of the cytoskeleton. By regulating the dynamics of microtubules and assembly of neuronal intermediate filaments (IFs), Ndel1 promotes neurite outgrowth, neuronal migration, and cell integrity (1-6). To further understand the roles of Ndel1 in cytoskeletal dynamics, we performed a tandem affinity purification of Ndel1-interacting proteins. We isolated a novel Ndel1 molecular complex composed of the IF vimentin, the molecular motor dynein, the lissencephaly protein Lis1, and the cis-Golgi-associated protein alphaCOP. Ndel1 promotes the interaction between Lis1, alphaCOP, and the vimentin-dynein complex. The functional result of this complex is activation of dynein-mediated transport of vimentin. A loss of Ndel1 functions by RNA interference fails to incorporate Lis1/alphaCOP in the complex, reduces the transport of vimentin, and culminates in IF accumulations and altered neuritogenesis. Our findings reveal a novel regulatory mechanism of vimentin transport during neurite extension that may have implications in diseases featuring transport/trafficking defects and impaired regeneration.

    View details for DOI 10.1074/jbc.M710200200

    View details for Web of Science ID 000255340000039

    View details for PubMedID 18303022

  • Ndel1 Promotes Axon Regeneration via Intermediate Filaments PLOS ONE Toth, C., Shim, S. Y., Wang, J., Jiang, Y., Neumayer, G., Belzil, C., Liu, W., Martinez, J., Zochodne, D., Nguyen, M. D. 2008; 3 (4)

    Abstract

    Failure of axons to regenerate following acute or chronic neuronal injury is attributed to both the inhibitory glial environment and deficient intrinsic ability to re-grow. However, the underlying mechanisms of the latter remain unclear. In this study, we have investigated the role of the mammalian homologue of aspergillus nidulans NudE, Ndel1, emergently viewed as an integrator of the cytoskeleton, in axon regeneration. Ndel1 was synthesized de novo and upregulated in crushed and transected sciatic nerve axons, and, upon injury, was strongly associated with neuronal form of the intermediate filament (IF) Vimentin while dissociating from the mature neuronal IF (Neurofilament) light chain NF-L. Consistent with a role for Ndel1 in the conditioning lesion-induced neurite outgrowth of Dorsal Root Ganglion (DRG) neurons, the long lasting in vivo formation of the neuronal Ndel1/Vimentin complex was associated with robust axon regeneration. Furthermore, local silencing of Ndel1 in transected axons by siRNA severely reduced the extent of regeneration in vivo. Thus, Ndel1 promotes axonal regeneration; activating this endogenous repair mechanism may enhance neuroregeneration during acute and chronic axonal degeneration.

    View details for DOI 10.1371/journal.pone.0002014

    View details for Web of Science ID 000261558700030

    View details for PubMedID 18431495

    View details for PubMedCentralID PMC2291557

  • Protein 600 is a microtubule/endoplasmic reticulum-associated protein in CNS neurons JOURNAL OF NEUROSCIENCE Shim, S. Y., Wang, J., Asada, N., Neumayer, G., Tran, H. C., Ishiguro, K., Sanada, K., Nakatani, Y., Nguyen, M. D. 2008; 28 (14): 3604-3614

    Abstract

    There is an increasing body of literature pointing to cytoskeletal proteins as spatial organizers and interactors of organelles. In this study, we identified protein 600 (p600) as a novel microtubule-associated protein (MAP) developmentally regulated in neurons. p600 exhibits the unique feature to interact with the endoplasmic reticulum (ER). Silencing of p600 by RNA interference (RNAi) destabilizes neuronal processes in young primary neurons undergoing neurite extension and containing scarce staining of the ER marker Bip. Furthermore, in utero electroporation of p600 RNAi alters neuronal migration, a process that depends on synergistic actions of microtubule dynamics and ER functions. p600-depleted migrating neurons display thin, crooked, and "zigzag" leading process with very few ER membranes. Thus, p600 constitutes the only known MAP to associate with the ER in neurons, and this interaction may impact on multiple cellular processes ranging from neuronal development to neuronal maturation and plasticity.

    View details for DOI 10.1523/JNEUROSCI.5278-07.2008

    View details for Web of Science ID 000254623500010

    View details for PubMedID 18385319

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