Honors & Awards


  • Genentech Foundation Predoctoral Fellowship, Genentech Foundation
  • Vanessa Kong Kerzner Graduate Fellowship, Stanford University School of Humanities and Sciences

Education & Certifications


  • BSc, Zhiyuan College, Shanghai Jiao Tong University (2014)

Stanford Advisors


Patents


  • Zhang Y, Li J, Xiao X. "China P.Rep. Patent ZL201420226963.9 A culture system and bioreactor for microorganisms", Shanghai Jiao Tong University

All Publications


  • A Defensive Kicking Behavior in Response to Mechanical Stimuli Mediated by Drosophila Wing Margin Bristles. journal of neuroscience Li, J., Zhang, W., Guo, Z., Wu, S., Jan, L. Y., Jan, Y. 2016; 36 (44): 11275-11282

    Abstract

    Mechanosensation, one of the fastest sensory modalities, mediates diverse behaviors including those pertinent for survival. It is important to understand how mechanical stimuli trigger defensive behaviors. Here, we report that Drosophila melanogaster adult flies exhibit a kicking response against invading parasitic mites over their wing margin with ultrafast speed and high spatial precision. Mechanical stimuli that mimic the mites' movement evoke a similar kicking behavior. Further, we identified a TRPV channel, Nanchung, and a specific Nanchung-expressing neuron under each recurved bristle that forms an array along the wing margin as being essential sensory components for this behavior. Our electrophysiological recordings demonstrated that the mechanosensitivity of recurved bristles requires Nanchung and Nanchung-expressing neurons. Together, our results reveal a novel neural mechanism for innate defensive behavior through mechanosensation.We discovered a previously unknown function for recurved bristles on the Drosophila melanogaster wing. We found that when a mite (a parasitic pest for Drosophila) touches the wing margin, the fly initiates a swift and accurate kick to remove the mite. The fly head is dispensable for this behavior. Furthermore, we found that a TRPV channel, Nanchung, and a specific Nanchung-expressing neuron under each recurved bristle are essential for its mechanosensitivity and the kicking behavior. In addition, touching different regions of the wing margin elicits kicking directed precisely at the stimulated region. Our experiments suggest that recurved bristles allow the fly to sense the presence of objects by touch to initiate a defensive behavior (perhaps analogous to touch-evoked scratching; Akiyama et al., 2012).

    View details for PubMedID 27807168

    View details for PubMedCentralID PMC5148243

  • A Genome-Scale Model of Shewanella piezotolerans Simulates Mechanisms of Metabolic Diversity and Energy Conservation. mSystems Dufault-Thompson, K., Jian, H., Cheng, R., Li, J., Wang, F., Zhang, Y. ; 2 (2)

    Abstract

    Shewanella piezotolerans strain WP3 belongs to the group 1 branch of the Shewanella genus and is a piezotolerant and psychrotolerant species isolated from the deep sea. In this study, a genome-scale model was constructed for WP3 using a combination of genome annotation, ortholog mapping, and physiological verification. The metabolic reconstruction contained 806 genes, 653 metabolites, and 922 reactions, including central metabolic functions that represented nonhomologous replacements between the group 1 and group 2 Shewanella species. Metabolic simulations with the WP3 model demonstrated consistency with existing knowledge about the physiology of the organism. A comparison of model simulations with experimental measurements verified the predicted growth profiles under increasing concentrations of carbon sources. The WP3 model was applied to study mechanisms of anaerobic respiration through investigating energy conservation, redox balancing, and the generation of proton motive force. Despite being an obligate respiratory organism, WP3 was predicted to use substrate-level phosphorylation as the primary source of energy conservation under anaerobic conditions, a trait previously identified in other Shewanella species. Further investigation of the ATP synthase activity revealed a positive correlation between the availability of reducing equivalents in the cell and the directionality of the ATP synthase reaction flux. Comparison of the WP3 model with an existing model of a group 2 species, Shewanella oneidensis MR-1, revealed that the WP3 model demonstrated greater flexibility in ATP production under the anaerobic conditions. Such flexibility could be advantageous to WP3 for its adaptation to fluctuating availability of organic carbon sources in the deep sea. IMPORTANCE The well-studied nature of the metabolic diversity of Shewanella bacteria makes species from this genus a promising platform for investigating the evolution of carbon metabolism and energy conservation. The Shewanella phylogeny is diverged into two major branches, referred to as group 1 and group 2. While the genotype-phenotype connections of group 2 species have been extensively studied with metabolic modeling, a genome-scale model has been missing for the group 1 species. The metabolic reconstruction of Shewanella piezotolerans strain WP3 represented the first model for Shewanella group 1 and the first model among piezotolerant and psychrotolerant deep-sea bacteria. The model brought insights into the mechanisms of energy conservation in WP3 under anaerobic conditions and highlighted its metabolic flexibility in using diverse carbon sources. Overall, the model opens up new opportunities for investigating energy conservation and metabolic adaptation, and it provides a prototype for systems-level modeling of other deep-sea microorganisms.

    View details for DOI 10.1128/mSystems.00165-16

    View details for PubMedID 28382331

    View details for PubMedCentralID PMC5371395

  • Transmembrane channel-like (tmc) gene regulates Drosophila larval locomotion PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Guo, Y., Wang, Y., Zhang, W., Meltzer, S., Zanini, D., Yu, Y., Li, J., Cheng, T., Guo, Z., Wang, Q., Jacobs, J. S., Sharma, Y., Eberl, D. F., Goepfert, M. C., Jan, L. Y., Jan, Y. N., Wang, Z. 2016; 113 (26): 7243-7248

    Abstract

    Drosophila larval locomotion, which entails rhythmic body contractions, is controlled by sensory feedback from proprioceptors. The molecular mechanisms mediating this feedback are little understood. By using genetic knock-in and immunostaining, we found that the Drosophila melanogaster transmembrane channel-like (tmc) gene is expressed in the larval class I and class II dendritic arborization (da) neurons and bipolar dendrite (bd) neurons, both of which are known to provide sensory feedback for larval locomotion. Larvae with knockdown or loss of tmc function displayed reduced crawling speeds, increased head cast frequencies, and enhanced backward locomotion. Expressing Drosophila TMC or mammalian TMC1 and/or TMC2 in the tmc-positive neurons rescued these mutant phenotypes. Bending of the larval body activated the tmc-positive neurons, and in tmc mutants this bending response was impaired. This implicates TMC's roles in Drosophila proprioception and the sensory control of larval locomotion. It also provides evidence for a functional conservation between Drosophila and mammalian TMCs.

    View details for DOI 10.1073/pnas.1606537113

    View details for Web of Science ID 000379033400072

    View details for PubMedID 27298354

    View details for PubMedCentralID PMC4932980

  • Ankyrin Repeats Convey Force to Gate the NOMPC Mechanotransduction Channel. Cell Zhang, W., Cheng, L. E., Kittelmann, M., Li, J., Petkovic, M., Cheng, T., Jin, P., Guo, Z., Göpfert, M. C., Jan, L. Y., Jan, Y. N. 2015; 162 (6): 1391-1403

    Abstract

    How metazoan mechanotransduction channels sense mechanical stimuli is not well understood. The NOMPC channel in the transient receptor potential (TRP) family, a mechanotransduction channel for Drosophila touch sensation and hearing, contains 29 Ankyrin repeats (ARs) that associate with microtubules. These ARs have been postulated to act as a tether that conveys force to the channel. Here, we report that these N-terminal ARs form a cytoplasmic domain essential for NOMPC mechanogating in vitro, mechanosensitivity of touch receptor neurons in vivo, and touch-induced behaviors of Drosophila larvae. Duplicating the ARs elongates the filaments that tether NOMPC to microtubules in mechanosensory neurons. Moreover, microtubule association is required for NOMPC mechanogating. Importantly, transferring the NOMPC ARs to mechanoinsensitive voltage-gated potassium channels confers mechanosensitivity to the chimeric channels. These experiments strongly support a tether mechanism of mechanogating for the NOMPC channel, providing insights into the basis of mechanosensitivity of mechanotransduction channels.

    View details for DOI 10.1016/j.cell.2015.08.024

    View details for PubMedID 26359990

    View details for PubMedCentralID PMC4568062

  • A transcriptional reporter of intracellular Ca(2+) in Drosophila. Nature neuroscience Gao, X. J., Riabinina, O., Li, J., Potter, C. J., Clandinin, T. R., Luo, L. 2015; 18 (6): 917-925

    Abstract

    Intracellular Ca(2+) is a widely used neuronal activity indicator. Here we describe a transcriptional reporter of intracellular Ca(2+) (TRIC) in Drosophila that uses a binary expression system to report Ca(2+)-dependent interactions between calmodulin and its target peptide. We found that in vitro assays predicted in vivo properties of TRIC and that TRIC signals in sensory systems depend on neuronal activity. TRIC was able to quantitatively monitor neuronal responses that changed slowly, such as those of neuropeptide F-expressing neurons to sexual deprivation and neuroendocrine pars intercerebralis cells to food and arousal. Furthermore, TRIC-induced expression of a neuronal silencer in nutrient-activated cells enhanced stress resistance, providing a proof of principle that TRIC can be used for circuit manipulation. Thus, TRIC facilitates the monitoring and manipulation of neuronal activity, especially those reflecting slow changes in physiological states that are poorly captured by existing methods. TRIC's modular design should enable optimization and adaptation to other organisms.

    View details for DOI 10.1038/nn.4016

    View details for PubMedID 25961791

    View details for PubMedCentralID PMC4446202

  • NAD(+)/NADH Metabolism and NAD(+)-Dependent Enzymes in Cell Death and Ischemic Brain Injury: Current Advances and Therapeutic Implications CURRENT MEDICINAL CHEMISTRY Ma, Y., Nie, H., Chen, H., Li, J., Hong, Y., Wang, B., Wang, C., Zhang, J., Cao, W., Zhang, M., Xu, Y., Ding, X., Yin, S. K., Qu, X., Ying, W. 2015; 22 (10): 1239-1247

    Abstract

    NAD(+) and NADH play crucial roles in a variety of biological processes including energy metabolism, mitochondrial functions, and gene expression. Multiple studies have indicated that NAD(+) administration can profoundly decrease oxidative cell death as well as ischemic and traumatic brain injury, suggesting NAD(+) metabolism as a promising therapeutic target for cerebral ischemia and head injury. Cumulating evidence has suggested that NAD(+) can produce its protective effects by multiple mechanisms, including preventing mitochondrial alterations, enhancing energy metabolism, preventing virtually all forms of cell death including apoptosis, necrosis and autophagy, inhibiting inflammation, directly increasing antioxidation capacity of cells and tissues, and activating SIRT1. Increasing evidence has also suggested that NADH metabolism is a potential therapeutic target for treating several neurological disorders. A number of studies have further indicated that multiple NAD(+)-dependent enzymes such as sirtuins, polymerase(ADP-ribose) polymerases (PARPs) and CD38 mediate cell death and multiple biological processes. In this article, an overview of the recent findings regarding the roles of NAD(+)/NADH and NAD(+)-dependent enzymes in cell death and ischemic brain injury is provided. These findings have collectively indicated that NAD(+)/NADH and NAD(+)-dependent enzymes play fundamental roles in oxidative stress-induced cell death and ischemic brain injury, which may become promising therapeutic targets for brain ischemia and multiple other neurological disorders.

    View details for Web of Science ID 000351160400008

    View details for PubMedID 25666794

  • Cytoplasmic Tyrosine Phosphatase Shp2 Coordinates Hepatic Regulation of Bile Acid and FGF15/19 Signaling to Repress Bile Acid Synthesis CELL METABOLISM Li, S., Hsu, D. D., Li, B., Luo, X., Alderson, N., Qiao, L., Ma, L., Zhu, H. H., He, Z., Suino-Powell, K., Ji, K., Li, J., Shao, J., Xu, H. E., Li, T., Feng, G. 2014; 20 (2): 320-332

    Abstract

    Bile acid (BA) biosynthesis is tightly controlled by intrahepatic negative feedback signaling elicited by BA binding to farnesoid X receptor (FXR) and also by enterohepatic communication involving ileal BA reabsorption and FGF15/19 secretion. However, how these pathways are coordinated is poorly understood. We show here that nonreceptor tyrosine phosphatase Shp2 is a critical player that couples and regulates the intrahepatic and enterohepatic signals for repression of BA synthesis. Ablating Shp2 in hepatocytes suppressed signal relay from FGFR4, receptor for FGF15/19, and attenuated BA activation of FXR signaling, resulting in elevation of systemic BA levels and chronic hepatobiliary disorders in mice. Acting immediately downstream of FGFR4, Shp2 associates with FRS2α and promotes the receptor activation and signal relay to several pathways. These results elucidate a molecular mechanism for the control of BA homeostasis by Shp2 through the orchestration of multiple signals in hepatocytes.

    View details for DOI 10.1016/j.cmet.2014.05.020

    View details for Web of Science ID 000341402500017

    View details for PubMedID 24981838

    View details for PubMedCentralID PMC4365973