Honors & Awards


  • K99, National Institute of Mental Health (2020)
  • Postdoctoral Fellowship, Deutsche Forschungsgemeinschaft (2016-2018)
  • PhD Fellowship, Friedrich-Ebert Stiftung (2012-2015)

Education & Certifications


  • PhD, University of Cambridge, Neurobiology (2016)
  • MSc, University of Heidelberg, Molecular Biosciences (2012)
  • BSc, University of Heidelberg, Molecular and Cellular Biology (2010)

All Publications


  • Dissecting neural mechanisms of prosocial behaviors. Current opinion in neurobiology Walsh, J. J., Christoffel, D. J., Wu, X., Pomrenze, M. B., Malenka, R. C. 2020; 68: 9–14

    Abstract

    Prosocial behaviors are essential for group cooperation, which enrich life experience and enhance survival. These complex behaviors are governed by intricate interactions between numerous neural circuits functioning in concert. Impairments in prosocial interactions result from disruptions of this coordinated brain activity and are a prominent feature of several pathological conditions including autism spectrum disorder, depression and addiction. Here we highlight recent studies that use advanced techniques to anatomically map, monitor and manipulate neural circuits that influence prosocial behavior. These recent findings provide important clues to unravel the complexities of the neural mechanisms that mediate prosocial interactions and offer insights into new strategies for the treatment of aberrant social behavior.

    View details for DOI 10.1016/j.conb.2020.11.006

    View details for PubMedID 33278639

  • Neuroligin-1 Signaling Controls LTP and NMDA Receptors by Distinct Molecular Pathways. Neuron Wu, X., Morishita, W. K., Riley, A. M., Hale, W. D., Sudhof, T. C., Malenka, R. C. 2019

    Abstract

    Neuroligins, postsynaptic cell adhesion molecules that are linked to neuropsychiatric disorders, are extensively studied, but fundamental questions about their functions remain. Using invivo replacement strategies in quadruple conditional knockout mice of all neuroligins to avoid heterodimerization artifacts, we show, in hippocampal CA1 pyramidal neurons, that neuroligin-1 performs two key functions in excitatory synapses by distinct molecular mechanisms. N-methyl-D-aspartate (NMDA) receptor-dependent LTP requires trans-synaptic binding of postsynaptic neuroligin-1 to presynaptic beta-neurexins but not the cytoplasmic sequences of neuroligins. In contrast, postsynaptic NMDA receptor (NMDAR)-mediated responses involve a neurexin-independent mechanism that requires the neuroligin-1 cytoplasmic sequences. Strikingly, deletion of neuroligins blocked the spine expansion associated with LTP, as monitored by two-photon imaging; this block involved a mechanism identical to that of therole of neuroligin-1 in NMDAR-dependent LTP. Our data suggest that neuroligin-1 performs two mechanistically distinct signaling functions and that neurolign-1-mediated trans-synaptic cell adhesion signaling critically regulates LTP.

    View details for PubMedID 30871858

  • Autophagy regulates Notch degradation and modulates stem cell development and neurogenesis. Nature communications Wu, X. n., Fleming, A. n., Ricketts, T. n., Pavel, M. n., Virgin, H. n., Menzies, F. M., Rubinsztein, D. C. 2016; 7: 10533

    Abstract

    Autophagy is a conserved, intracellular, lysosomal degradation pathway. While mechanistic aspects of this pathway are increasingly well defined, it remains unclear how autophagy modulation impacts normal physiology. It is, however, becoming clear that autophagy may play a key role in regulating developmental pathways. Here we describe for the first time how autophagy impacts stem cell differentiation by degrading Notch1. We define a novel route whereby this plasma membrane-resident receptor is degraded by autophagy, via uptake into ATG16L1-positive autophagosome-precursor vesicles. We extend our findings using a physiologically relevant mouse model with a hypomorphic mutation in Atg16L1, a crucial autophagy gene, which shows developmental retention of early-stage cells in various tissues where the differentiation of stem cells is retarded and thus reveal how modest changes in autophagy can impact stem cell fate. This may have relevance for diverse disease conditions, like Alzheimer's Disease or Crohn's Disease, associated with altered autophagy.

    View details for DOI 10.1038/ncomms10533

    View details for PubMedID 26837467

    View details for PubMedCentralID PMC4742842

  • CCT complex restricts neuropathogenic protein aggregation via autophagy. Nature communications Pavel, M. n., Imarisio, S. n., Menzies, F. M., Jimenez-Sanchez, M. n., Siddiqi, F. H., Wu, X. n., Renna, M. n., O'Kane, C. J., Crowther, D. C., Rubinsztein, D. C. 2016; 7: 13821

    Abstract

    Aberrant protein aggregation is controlled by various chaperones, including CCT (chaperonin containing TCP-1)/TCP-1/TRiC. Mutated CCT4/5 subunits cause sensory neuropathy and CCT5 expression is decreased in Alzheimer's disease. Here, we show that CCT integrity is essential for autophagosome degradation in cells or Drosophila and this phenomenon is orchestrated by the actin cytoskeleton. When autophagic flux is reduced by compromise of individual CCT subunits, various disease-relevant autophagy substrates accumulate and aggregate. The aggregation of proteins like mutant huntingtin, ATXN3 or p62 after CCT2/5/7 depletion is predominantly autophagy dependent, and does not further increase with CCT knockdown in autophagy-defective cells/organisms, implying surprisingly that the effect of loss-of-CCT activity on mutant ATXN3 or huntingtin oligomerization/aggregation is primarily a consequence of autophagy inhibition rather than loss of physiological anti-aggregation activity for these proteins. Thus, our findings reveal an essential partnership between two key components of the proteostasis network and implicate autophagy defects in diseases with compromised CCT complex activity.

    View details for DOI 10.1038/ncomms13821

    View details for PubMedID 27929117

    View details for PubMedCentralID PMC5155164

  • Autophagy and mammalian development. Biochemical Society transactions Wu, X. n., Won, H. n., Rubinsztein, D. C. 2013; 41 (6): 1489–94

    Abstract

    Autophagy is a highly conserved cytoplasmic degradation pathway that has an impact on many physiological and disease states, including immunity, tumorigenesis and neurodegeneration. Recent studies suggest that autophagy may also have important functions in embryogenesis and development. Many autophagy gene-knockout mice have embryonic lethality at different stages of development. Furthermore, interactions of autophagy with crucial developmental pathways such as Wnt, Shh (Sonic Hedgehog), TGFβ (transforming growth factor β) and FGF (fibroblast growth factor) have been reported. This suggests that autophagy may regulate cell fate decisions, such as differentiation and proliferation. In the present article, we discuss how mammalian autophagy may affect phenotypes associated with development.

    View details for DOI 10.1042/BST20130185

    View details for PubMedID 24256242