Bio

Honors & Awards


  • Wu-Shunde Couple Scholarship, Tsinghua University, China (2003)
  • National Scholarship First-class, Tsinghua University and Ministry of Education (China) (2004)
  • Outstanding Graduate Student Research Scholarship, Tsinghua University, China (2009-2011)
  • C B. Carringtong Memorial Award, Department of Pathology, Stanford University School of Medicine (2013)
  • Dean’s Postdoctoral Fellowship, Stanford University School of Medicine (2013-2014)

Professional Education


  • Doctor of Philosophy, Tsinghua University (2010)

Stanford Advisors


Research & Scholarship

Current Research and Scholarly Interests


mechanism of Parkinson's disease, Alzheimer's disease, and other rare genetic degenerative diseases.

Used to work on NBIA and metal induced neurodegeneration.

Publications

Journal Articles


  • RNA Metabolism in the Pathogenesis of Parkinson's Disease. Brain research Lu, B., Gehrke, S., Wu, Z. 2014

    Abstract

    Neurodegenerative diseases such as Parkinson's disease are progressive disorders of the nervous system that affect the function and maintenance of specific neuronal populations. While most disease cases are sporadic with no known cause, a small percentage of disease cases is caused by inherited genetic mutations. The identification of genes associated with the familial forms of the diseases and subsequent studies of proteins encoded by the disease genes in cellular or animals models have offered much-needed insights into the molecular and cellular mechanisms underlying disease pathogenesis. Recent studies of the familial Parkinson's disease genes have emphasized the importance of RNA metabolism, particularly mRNA translation, in the disease process. It is anticipated that continued studies on the role of RNA metabolism in Parkinson's disease will offer unifying mechanisms for understanding the cause of neuronal dysfunction and degeneration and facilitate the development of novel and rational strategies for treating this debilitating disease.

    View details for DOI 10.1016/j.brainres.2014.03.003

    View details for PubMedID 24631951

  • Roles of PINK1, mTORC2, and mitochondria in preserving brain tumor-forming stem cells in a noncanonical Notch signaling pathway. Genes & development Lee, K., Wu, Z., Song, Y., Mitra, S. S., Feroze, A. H., Cheshier, S. H., Lu, B. 2013; 27 (24): 2642-2647

    Abstract

    The self-renewal versus differentiation choice of Drosophila and mammalian neural stem cells (NSCs) requires Notch (N) signaling. How N regulates NSC behavior is not well understood. Here we show that canonical N signaling cooperates with a noncanonical N signaling pathway to mediate N-directed NSC regulation. In the noncanonical pathway, N interacts with PTEN-induced kinase 1 (PINK1) to influence mitochondrial function, activating mechanistic target of rapamycin complex 2 (mTORC2)/AKT signaling. Importantly, attenuating noncanonical N signaling preferentially impaired the maintenance of Drosophila and human cancer stem cell-like tumor-forming cells. Our results emphasize the importance of mitochondria to N and NSC biology, with important implications for diseases associated with aberrant N signaling.

    View details for DOI 10.1101/gad.225169.113

    View details for PubMedID 24352421

  • Tricornered/NDR kinase signaling mediates PINK1-directed mitochondrial quality control and tissue maintenance GENES & DEVELOPMENT Wu, Z., Sawada, T., Shiba, K., Liu, S., Kanao, T., Takahashi, R., Hattori, N., Imai, Y., Lu, B. 2013; 27 (2): 157-162

    Abstract

    Eukaryotes employ elaborate mitochondrial quality control (MQC) to maintain the function of the power-generating organelle. Parkinson's disease-associated PINK1 and Parkin actively participate in MQC. However, the signaling events involved are largely unknown. Here we show that mechanistic target of rapamycin 2 (mTORC2) and Tricornered (Trc) kinases act downstream from PINK1 to regulate MQC. Trc is phosphorylated in mTORC2-dependent and mTORC2-independent manners and is specifically localized to mitochondria in response to PINK1, which regulates mTORC2 through mitochondrial complex-I activity. Genetically, mTORC2 and Trc act upstream of Parkin. Thus, multiplex kinase signaling is acting between PINK1 and Parkin to regulate MQC, a process highly conserved in mammals.

    View details for DOI 10.1101/gad.203406.112

    View details for Web of Science ID 000314044800005

    View details for PubMedID 23348839

  • Mitochondrial release of the NADH dehydrogenase Ndi1 induces apoptosis in yeast MOLECULAR BIOLOGY OF THE CELL Cui, Y., Zhao, S., Wu, Z., Dai, P., Zhou, B. 2012; 23 (22): 4373-4382

    Abstract

    Saccharomyces cerevisiae NDI1 codes for the internal mitochondrial ubiquinone oxidoreductase, which transfers electrons from NADH to ubiquinone in the respiratory chain. Previously we found that Ndi1 is a yeast homologue of the protein apoptosis-inducing factor-homologous mitochondrion-associated inducer of death and displays potent proapoptotic activity. Here we show that S. cerevisiae NDI1 is involved in apoptosis induced by various stimuli tested, including H(2)O(2), Mn, and acetate acid, independent of Z-VAD-fmk (a caspase inhibitor) inhibition. Although Ndi1 also participates in respiration, its proapoptotic property is separable from the ubiquinone oxidoreductase activity. During apoptosis, the N-terminal of Ndi1 is cleaved off in the mitochondria, and this activated form then escapes out to execute its apoptotic function. The N-terminal cleavage appears to be essential for the manifestation of the full apoptotic activity, as the uncleaved form of Ndi1 exhibits much less growth-inhibitory activity. Our results thus indicate an important role of Ndi1 in the switch of life and death fates in yeast: during normal growth, Ndi1 assimilates electrons to the electron transport chain and initiates the respiration process to make ATP, whereas under stresses, it cleaves the toxicity-sequestering N-terminal cap, is released from the mitochondria, and becomes a cell killer.

    View details for DOI 10.1091/mbc.E12-04-0281

    View details for Web of Science ID 000314404700004

    View details for PubMedID 22993213

  • Aluminum induces neurodegeneration and its toxicity arises from increased iron accumulation and reactive oxygen species (ROS) production NEUROBIOLOGY OF AGING Wu, Z., Du, Y., Xue, H., Wu, Y., Zhou, B. 2012; 33 (1)

    Abstract

    The neurotoxicity of aluminum (Al) - the most abundant metal element on earth - has been known for years. However, the mechanism of Al-induced neurodegeneration and its relationship to Alzheimer's disease are still controversial. In particular, in vivo functional data are lacking. In a Drosophila model with chronic dietary Al overloading, general neurodegeneration and several behavioral changes were observed. Al-induced neurodegeneration is independent of ?-amyloid or tau-associated toxicity, suggesting they act in different molecular pathways. Interestingly, Drosophila frataxin (dfh), which causes Friedreich's ataxia if mutated in humans, displayed an interacting effect with Al, suggesting Friedreich's ataxia patients might be more susceptible to Al toxicity. Al-treated flies accumulated large amount of iron and reactive oxygen species (ROS), and exhibited elevated SOD2 activity. Genetic and pharmacological efforts to reduce ROS or chelate excess Fe significantly mitigated Al toxicity. Our results indicate that Al toxicity is mediated through ROS production and iron accumulation and suggest a remedial route to reduce toxicity due to Al exposure.

    View details for DOI 10.1016/j.neurobiolaging.2010.06.018

    View details for Web of Science ID 000297934700031

    View details for PubMedID 20674094

  • Pantothenate kinase-associated neurodegeneration: insights from a Drosophila model HUMAN MOLECULAR GENETICS Wu, Z., Li, C., Lv, S., Zhou, B. 2009; 18 (19): 3659-3672

    Abstract

    Pantothenate-Kinase-Associated-Neurodegeneration (PKAN) is a devastating disease, resulting from mutations in pantothenate kinase 2 (PANK2), one of the four human pantothenate kinase genes (PANK1-4). Interestingly, PanK2 appears to be the only mitochondria-targeted human PanK. It is unknown whether the mitochondria-targeted PanK is associated with any unique function, nor whether PKAN is due solely to the loss of pantothenate kinase activity. Drosophila PANK [fumble (fbl)] encodes several isoforms of pantothenate kinase products, one of which localizes to mitochondria and the others cytosol. fbl flies exhibit many characteristic features reminiscent of PKAN patients. Various forms of Drosophila fbl and human PANK2 were introduced into fbl flies to study their in vivo functions. Only mitochondria-targeted Fbl or human PanK2 was able to rescue fbl mutation, with the rescuing ability sensitive to the expression level of the transgene. Transgenic lines with low expression of normal Fbl or PanK2 displayed similar phenotypes as PANK2 mutant transgenic flies. These PanK2 mutants all showed reduced and phenotype severity-correlated in vitro pantothenate kinase activities. Amazingly, cytosolic PanK3 and PanK4 could mostly, but not fully, rescue fbl defects except the male sterility. Therefore, fbl appears to be the orthologue of human PANK2, and PanK2 is functionally more potent than PanK3 and PanK4 in vivo. We suggest that mitochondria-located pantothenate kinase is required to achieve the maximal enzymatic activity to fulfill the most challenging task such as maintaining male fertility and optimal neuronal functions, and PKAN features are mainly due to the reduction of the total cellular pantothenate kinase activity in the most susceptible regions.

    View details for DOI 10.1093/hmg/ddp314

    View details for Web of Science ID 000270707900012

    View details for PubMedID 19602483

  • Dietary rescue of fumble - a Drosophila model for pantothenate-kinase-associated neurodegeneration JOURNAL OF INHERITED METABOLIC DISEASE Yang, Y., Wu, Z., Kuo, Y. M., Zhou, B. 2005; 28 (6): 1055-1064

    Abstract

    Hallervorden-Spatz syndrome (HSS) is a devastating neurological disease, characterized by iron accumulation in the globus pallidus in the basal ganglia. Most HSS cases are caused by mutations in one of the four human pantothenate kinases (PANK2). This PANK2-caused subgroup of HSS is sometimes referred as PKAN (pantothenate-kinase-associated neurodegeneration). No effective treatment for PKAN or HSS is currently available. fumble, a Drosophila mutant that carries a mutation in Drosophila Pank, has many features similar to those of PKAN patients. In this study, we used fumble as a model to evaluate various compounds or nutritional products for their possible therapeutic efficacy. While no product was found to dramatically improve the symptoms, GKE (containing Ginkgo biloba extract and flavone) and vitamin E showed statistically significant beneficial effects. Our studies indicate that pantothenate is of limited value in alleviating fumble phenotypes and also suggest that some compounds might have deleterious effects.

    View details for DOI 10.1007/s10545-005-0200-0

    View details for Web of Science ID 000234907300028

    View details for PubMedID 16435199

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