Professional Education

  • Doctor of Philosophy, Baylor College Of Medicine (2016)
  • Bachelor of Science, Tsinghua University (2009)

Stanford Advisors

All Publications

  • Classifying Drosophila Olfactory Projection Neuron Subtypes by Single-Cell RNA Sequencing. Cell Li, H., Horns, F., Wu, B., Xie, Q., Li, J., Li, T., Luginbuhl, D. J., Quake, S. R., Luo, L. 2017; 171 (5)
  • Loss of Frataxin induces iron toxicity, sphingolipid synthesis, and Pdkl/Mef2 activation, leading to neurodegeneration ELIFE Chen, K., Lin, G., Haelterman, N. A., Ho, T. S., Li, T., Li, Z., Duraine, L., Graham, B. H., Jaiswal, M., Yamamoto, S., Rasband, M. N., Bellen, H. J. 2016; 5


    Mutations in Frataxin (FXN) cause Friedreich's ataxia (FRDA), a recessive neurodegenerative disorder. Previous studies have proposed that loss of FXN causes mitochondrial dysfunction, which triggers elevated reactive oxygen species (ROS) and leads to the demise of neurons. Here we describe a ROS independent mechanism that contributes to neurodegeneration in fly FXN mutants. We show that loss of frataxin homolog (fh) in Drosophila leads to iron toxicity, which in turn induces sphingolipid synthesis and ectopically activates 3-phosphoinositide dependent protein kinase-1 (Pdk1) and myocyte enhancer factor-2 (Mef2). Dampening iron toxicity, inhibiting sphingolipid synthesis by Myriocin, or reducing Pdk1 or Mef2 levels, all effectively suppress neurodegeneration in fh mutants. Moreover, increasing dihydrosphingosine activates Mef2 activity through PDK1 in mammalian neuronal cell line suggesting that the mechanisms are evolutionarily conserved. Our results indicate that an iron/sphingolipid/Pdk1/Mef2 pathway may play a role in FRDA.

    View details for DOI 10.7554/eLife.16043

    View details for Web of Science ID 000380920100001

    View details for PubMedID 27343351

    View details for PubMedCentralID PMC4956409

  • The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in the auditory organs of Drosophila and mammals ELIFE Li, T., Giagtzoglou, N., Eberl, D. F., Jaiswal, S. N., Cai, T., Godt, D., Groves, A. K., Bellen, H. J. 2016; 5


    Myosins play essential roles in the development and function of auditory organs and multiple myosin genes are associated with hereditary forms of deafness. Using a forward genetic screen in Drosophila, we identified an E3 ligase, Ubr3, as an essential gene for auditory organ development. Ubr3 negatively regulates the mono-ubiquitination of non-muscle Myosin II, a protein associated with hearing loss in humans. The mono-ubiquitination of Myosin II promotes its physical interaction with Myosin VIIa, a protein responsible for Usher syndrome type IB. We show that ubr3 mutants phenocopy pathogenic variants of Myosin II and that Ubr3 interacts genetically and physically with three Usher syndrome proteins. The interactions between Myosin VIIa and Myosin IIa are conserved in the mammalian cochlea and in human retinal pigment epithelium cells. Our work reveals a novel mechanism that regulates protein complexes affected in two forms of syndromic deafness and suggests a molecular function for Myosin IIa in auditory organs.

    View details for DOI 10.7554/eLife.15258

    View details for Web of Science ID 000380918600001

    View details for PubMedID 27331610

    View details for PubMedCentralID PMC4978524

  • Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination PLOS GENETICS Li, T., Fan, J., Blanco-Sanchez, B., Giagtzoglou, N., Lin, G., Yamamoto, S., Jaiswal, M., Chen, K., Zhang, J., Wei, W., Lewis, M. T., Groves, A. K., Westerfield, M., Jia, J., Bellen, H. J. 2016; 12 (5)


    Hedgehog (Hh) signaling regulates multiple aspects of metazoan development and tissue homeostasis, and is constitutively active in numerous cancers. We identified Ubr3, an E3 ubiquitin ligase, as a novel, positive regulator of Hh signaling in Drosophila and vertebrates. Hh signaling regulates the Ubr3-mediated poly-ubiquitination and degradation of Cos2, a central component of Hh signaling. In developing Drosophila eye discs, loss of ubr3 leads to a delayed differentiation of photoreceptors and a reduction in Hh signaling. In zebrafish, loss of Ubr3 causes a decrease in Shh signaling in the developing eyes, somites, and sensory neurons. However, not all tissues that require Hh signaling are affected in zebrafish. Mouse UBR3 poly-ubiquitinates Kif7, the mammalian homologue of Cos2. Finally, loss of UBR3 up-regulates Kif7 protein levels and decreases Hh signaling in cultured cells. In summary, our work identifies Ubr3 as a novel, evolutionarily conserved modulator of Hh signaling that boosts Hh in some tissues.

    View details for DOI 10.1371/journal.pgen.1006054

    View details for Web of Science ID 000377197100054

    View details for PubMedID 27195754

    View details for PubMedCentralID PMC4873228

  • Pri sORF peptides induce selective proteasome-mediated protein processing SCIENCE Zanet, J., Benrabah, E., Li, T., Pelissier-Monier, A., Chanut-Delalande, H., Ronsin, B., Bellen, H. J., Payre, F., Plaza, S. 2015; 349 (6254): 1356-1358


    A wide variety of RNAs encode small open-reading-frame (smORF/sORF) peptides, but their functions are largely unknown. Here, we show that Drosophila polished-rice (pri) sORF peptides trigger proteasome-mediated protein processing, converting the Shavenbaby (Svb) transcription repressor into a shorter activator. A genome-wide RNA interference screen identifies an E2-E3 ubiquitin-conjugating complex, UbcD6-Ubr3, which targets Svb to the proteasome in a pri-dependent manner. Upon interaction with Ubr3, Pri peptides promote the binding of Ubr3 to Svb. Ubr3 can then ubiquitinate the Svb N terminus, which is degraded by the proteasome. The C-terminal domains protect Svb from complete degradation and ensure appropriate processing. Our data show that Pri peptides control selectivity of Ubr3 binding, which suggests that the family of sORF peptides may contain an extended repertoire of protein regulators.

    View details for DOI 10.1126/science.aac5677

    View details for Web of Science ID 000361357700053

    View details for PubMedID 26383956

  • A Drosophila Genetic Resource of Mutants to Study Mechanisms Underlying Human Genetic Diseases CELL Yamamoto, S., Jaiswal, M., Charng, W., Gambin, T., Karaca, E., Mirzaa, G., Wiszniewski, W., Sandoval, H., Haelterman, N. A., Xiong, B., Zhang, K., Bayat, V., David, G., Li, T., Chen, K., Gala, U., Harel, T., Pehlivan, D., Penney, S., Vissers, L. E., de Ligt, J., Jhangiani, S. N., Xie, Y., Tsang, S. H., Parman, Y., Sivaci, M., Battaloglu, E., Muzny, D., Wan, Y., Liu, Z., Lin-Moore, A. T., Clark, R. D., Curry, C. J., Link, N., Schulze, K. L., Boerwinkle, E., Dobyns, W. B., Allikmets, R., Gibbs, R. A., Chen, R., Lupski, J. R., Wangler, M. F., Bellen, H. J. 2014; 159 (1): 200-214


    Invertebrate model systems are powerful tools for studying human disease owing to their genetic tractability and ease of screening. We conducted a mosaic genetic screen of lethal mutations on the Drosophila X chromosome to identify genes required for the development, function, and maintenance of the nervous system. We identified 165 genes, most of whose function has not been studied in vivo. In parallel, we investigated rare variant alleles in 1,929 human exomes from families with unsolved Mendelian disease. Genes that are essential in flies and have multiple human homologs were found to be likely to be associated with human diseases. Merging the human data sets with the fly genes allowed us to identify disease-associated mutations in six families and to provide insights into microcephaly associated with brain dysgenesis. This bidirectional synergism between fly genetics and human genomics facilitates the functional annotation of evolutionarily conserved genes involved in human health.

    View details for DOI 10.1016/j.cell.2014.09.002

    View details for Web of Science ID 000343095000020

    View details for PubMedID 25259927

    View details for PubMedCentralID PMC4298142

  • Drosophila EHBP1 regulates Scabrous secretion during Notch-mediated lateral inhibition JOURNAL OF CELL SCIENCE Giagtzoglou, N., Li, T., Yamamoto, S., Bellen, H. J. 2013; 126 (16): 3686-3696


    Notch signaling is an evolutionarily conserved pathway that plays a central role in numerous developmental and disease processes. The versatility of the Notch pathway relies on the activity of context-dependent regulators. These include rab11, sec15, arp3 and Drosophila EHBP1 (dEHBP1), which control Notch signaling and cell fate acquisition in asymmetrically dividing mechanosensory lineages by regulating the trafficking of the ligand Delta. Here, we show that dEHBP1 also controls the specification of R8 photoreceptors, as its loss results in the emergence of supernumerary R8 photoreceptors. Given the requirements for Notch signaling during lateral inhibition, we propose that dEHBP1 regulates distinct aspects of Notch signaling in different developmental contexts. We show that dEHBP1 regulates the exocytosis of Scabrous, a positive regulator of Notch signaling. In conclusion, dEHBP1 provides developmental versatility of intercellular signaling by regulating the trafficking of distinct Notch signaling components.

    View details for DOI 10.1242/jcs.126292

    View details for Web of Science ID 000323204400018

    View details for PubMedID 23788431

    View details for PubMedCentralID PMC3744027

  • Crag Is a GEF for Rab11 Required for Rhodopsin Trafficking and Maintenance of Adult Photoreceptor Cells PLOS BIOLOGY Xiong, B., Bayat, V., Jaiswal, M., Zhang, K., Sandoval, H., Charng, W., Li, T., David, G., Duraine, L., Lin, Y., Neely, G. G., Yamamoto, S., Bellen, H. J. 2012; 10 (12)


    Rhodopsins (Rhs) are light sensors, and Rh1 is the major Rh in the Drosophila photoreceptor rhabdomere membrane. Upon photoactivation, a fraction of Rh1 is internalized and degraded, but it remains unclear how the rhabdomeric Rh1 pool is replenished and what molecular players are involved. Here, we show that Crag, a DENN protein, is a guanine nucleotide exchange factor for Rab11 that is required for the homeostasis of Rh1 upon light exposure. The absence of Crag causes a light-induced accumulation of cytoplasmic Rh1, and loss of Crag or Rab11 leads to a similar photoreceptor degeneration in adult flies. Furthermore, the defects associated with loss of Crag can be partially rescued with a constitutive active form of Rab11. We propose that upon light stimulation, Crag is required for trafficking of Rh from the trans-Golgi network to rhabdomere membranes via a Rab11-dependent vesicular transport.

    View details for DOI 10.1371/journal.pbio.1001438

    View details for Web of Science ID 000312905300002

    View details for PubMedID 23226104

    View details for PubMedCentralID PMC3514319