Prof. Hongjie ZHANG

Education
DEng	University of Tokushima, Tokushima, Japan
MEng	Zhengzhou University, Zhengzhou, China
BEng	Zhengzhou University, Zhengzhou, China

Positions
2021 – Present	Associate Professor, Faculty of Health Sciences, University of Macau
2015 – 2021	Assistant Professor, Faculty of Health Sciences, University of Macau
2011 – 2014	Instructor, Massachusetts General Hospital/Harvard Medical School, Boston, USA
2006 – 2011	Research fellow, Massachusetts General Hospital/Harvard Medical School, Boston, USA
2003 – 2006	Postdoctoral fellow, Albert Einstein College of Medicine, New York, USA
2003	Lecturer, University of Tokushima, Tokushima, Japan

Research Interests

The main research interest of our group is focused on the molecular mechanism of organ morphogenesis. Majority of human diseases are originated from internal organs. Understanding the molecular mechanism of organ formation and maintenance is fundamental to developmental biology and medicine. However, currently the process of organ morphogenesis is not possible to be examined in complex organisms in vivo. We use genetically tractable and structurally simple C. elegans as a model system, employing genetic, biochemical and functional genomics approaches to investigate how organs form and how the shape and size of organs are regulated and maintained.We are also interested in in vivo sphingolipid (SL) homeostatic network regulation. SLs are involved in a wide array of cellular processes and are affected in a variety of diseases ranging from diabetes to cancer, from neurodegenerative- to cardiovascular diseases. Yet, little is known about their roles in the development of these diseases and their potential to serve as drugs or treatment targets. We use the C. elegans model, with a simple set of conserved SLs, to delineate the SL homeostatic network and its regulation on the whole organism level and to explore the link between SL metabolites and the pathology of the diseases linked to defects in SL biosynthesis and metabolism.

Representative Publications

Cheng, X., Zhang, P., Zhao, , Zheng, H., Zheng, K., Zhang, H., Zhang, H.#, 2022. Proteotoxic stress disrupts epithelial integrity by inducing mTOR sequestration and autophagy overactivation. Autophagy, doi: 10.1080/15548627.2022.2071381. Cui, M., Gobel, V., Zhang, H. #, 2021. Uncovering the “Sphinx” of Sphingosine 1-Phosphate Signaling: from Cellular Events to Organ Morphogenesis. Biol Rev Camb Philos Soc, doi: 10.1111/brv.12798. Li, Z., Zhang, P., Zhang, R., Wang, X., Tse, YC, Zhang, H. #, 2021. A collection of toolkit strains reveals distinct localization and dynamics of membrane-associated transcripts in epithelia. Cell Rep 35, 109072. Gao, J., Zhao, L., Luo, Q., Liu, S., Lin, Z., Wang, P., Fu, X., Chen, J., Zhang, H., Lin, L., Shi, A., 2020. An EHBP-1-SID-3-DYN-1 axis promotes membranous tubule fission during endocytic recycling. PLoS Genet 16, 1-28. Zhang, W., Xie, R., Zhang, X.D., Lee, T. O., Zhang, H., Yang, M., Peng, B., Zheng, J. , 2020. Organism Dual RNA-seq Reveals the Importance of BarA/UvrY in Vibrio Parahaemolyticus Virulence. FASEB J 34, 7561-7577. Cui, M., Ying, R., Jiang, X., Li, G., Zhang, X., Zheng, J., Tam, K. Y., Liang, B., Shi, A., Gobel, V., Zhang, H.#, 2019. A model of hereditary sensory and autonomic neuropathy type 1 reveals a role of glycosphingolipids in neuronal polarity. J Neurosci 39, 5816-5834. (Cover story) Cheng, X., Jiang, X., Tam, K. Y., Li, G., Zheng, J., Zhang, H.#, 2019. Sphingolipidomic analysis of C. elegans reveals development- and environment-dependent metabolic features. Int J Biol Sci 15, 2897-2910. Khan, L., Jafari, G., Zhang, N., Membreno, E., Yan, S., Zhang, H., Gobel, V., 2019. A tensile trilayered cytoskeletal endotube drives capillary-like lumenogenesis. J Cell Biol 218, 2403-2424. Ji, X., Zou, J., Peng, H., Stolle, A.S., Xie, R., Zhang, H., Peng, B., Mekalanos, J., Zheng, J., 2019. Alarmone Ap4A is elevated by aminoglycoside antibiotics and enhances their bactericidal activity. Proc Natl Acad Sci USA 116, 9578-9585. Zhang, T., Guan, X., Choi, U.L, Dong, Q., Lam, M.M.T., Zeng, J., Xiong, J., Wang, X., Poon, C. W., Zhang, H., Zhang, X., Wang, H., Xie, R., Zhu, B., Li, G., 2019. Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation. Epigenetics & Chromatin 12, 32-1-32-17. Deng, H., Guan, G., Gong, L., Zeng, J., Zhang, H., Chen, M.Y., Li, G., 2019. CBX6 is negatively regulated by EZH2 and plays a potential tumor suppressor role in breast cancer. Sci Rep 9, 197-1-197-13. Wang, C., Cheng, X., Tan, J., Ding, Z., Wang, W., Yuan, D., Li, G., Zhang, H.#, Zhang, X., 2018. Reductive cleavage of C=C bond as a new strategy to turn on dual fluorescence for effective sensing H2S. Chem Sci 9, 8369-8374. (# co-corresponding author). Zou, J., Zhang, W., Zhang, H., Zhang, X.D., Peng, B., Zheng, J., 2018. Studies on Aminoglycoside Susceptibility Identify a Novel Function of KsgA to Secure Protein Translational Fidelity during Antibiotic Stress. Antimicrob Agents Ch 62, e00853-18. Deng, H., Zeng, J., Zhang, T., Gong, L., Zhang, H., Cheung, C. W., Jones, C., Li, G., 2018. Histone H3. 3K27M Mobilizes Multiple Cancer/Testis (CT) Antigens in Pediatric Glioma. Mol Cancer Res 16, 623-633. Cheng, X., Zheng, J., Li, G., Göbel , V., Zhang, H.#, 2018. Degradation for better survival? Role of ubiquitination in epithelial morphogenesis. Biol Rev Camb Philos Soc 93, 1438-1460. Zhang, N., Khan, L., Membrano, E., Jafari, G., Yan, S., Zhang, H.#, Gobel, V., 2017. The C. elegans intestine as a model for intercellular lumen morphogenesis and in vivo polarized membrane biogenesis at the single-cell level: Labeling by Antibody Staining, RNAi Loss-of-function Analysis and Imaging. J Vis Exp 128, e56100, doi:10.3791/56100. (# co-corresponding author) Zhang, N., Membrano, E., Raj, S., Zhang, H., Khan, L., Gobel, V., 2017. The C. elegans excretory canal as a model for intracellular lumen morphogenesis and in vivo polarized membrane biogenesis in a single cell: labeling by GFP-fusions, RNAi Interaction Screen and Imaging. J Vis Exp 128, e56101, doi:10.3791/56101. Zhang, H., Abraham, N., Khan, L., Gobel, V., 2015. RNAi-based biosynthetic pathway screens to identify in vivo functions of non-nucleic-acid-based metabolites such as lipids. Nat Protoc 10, 681-700. Khan, L., Zhang, H., Abraham, N., Sun, L., Fleming, J., Buechner, M., Hall, D., Gobel, V., 2013. Intracellular lumen extension requires ERM-1-dependent apical membrane expansion and AQP-8-mediated flux. Nat Cell Biol 15, 143-156. (Featured as News & Views Article in the same journal.) Zhang, H., Kim, A., Abraham, N., Hall, D., Fleming, J., Gobel, V., 2012. Clathrin and AP-1 mediate apical polarity and lumen formation in C. elegans tubulogenesis. Development 139, 2071-2083. Zhang, H., Abraham, N., Khan, L., Hall, D., Fleming, J., Gobel, V., 2011. Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis. Nat Cell Biol 13, 1189-1201. (Featured as News & Views Article in the same journal, cited by Faculty of 1000 and highlighted as Editor’s Choice in Science.) Zhang, H., Emmons, S., 2009. Regulation of the Caenorhabditis elegans posterior Hox gene egl-5 by microRNA and the polycomb-like gene sop-2. Dev Dyn 238, 595-603. Mito, T., Kobayashi, C., Sarashina, I., Zhang, H., Shinahara, W., Miyawaki, K., Shinmyo, Y., Ohuchi, H., Noji, S., 2007. even-skipped has gap-like, pair-rule-like, and segmental functions in the cricket Gryllus bimaculatus, a basal, intermediate germ insect (Orthoptera). Dev Biol 303, 202-213. Mito, T., Sarashina, I., Zhang, H., Iwahashi, A., Okamoto, H., Miyawaki, K., Shinmyo, Y., Ohuchi, H., Noji, S., 2005. Non-canonical functions of hunchback in segment patterning of the intermediate germ cricket Gryllus bimaculatus. Development 132, 2069-2079. Zhang, H., Shinmyo, Y., Mito, T., Miyawaki, K., Sarashina, I., Ohuchi, H., Noji, S., 2005. Expression pattern of homeotic genes Scr, Antp, Ubx and abd-A during embryogenesis of the cricket Gryllus bimaculatus. Gene Expr Patterns 5, 491-502. Zhang, H., Shinmyo, Y., Hirose, A., Mito, T., Inoue, Y., Ohuchi, H., Loukeris, T., Eggleston, P., Noji, S., 2002. Extrachromosomal Transposition of the Transposable Element Minos Occurs in Embryos of the Cricket Gryllus bimaculatus, Dev Growth Differ 44, 409-417. Miywaki, K., Mito, T., Sarashina, I., Zhang, H., Shinmyo, Y., Ohuchi, H., Noji, S., 2004. Involvement of Wingless/Armadillo signaling in the posterior sequential segmentation in the cricket, Gryllus bimaculatus (Orthoptera), as revealed by RNAi analysis. Mech Dev 121, 119-30.

Research Grants
06/2021 – 06/2024	Deciphering the mRNP code in epithelial morphogenesis, The Science and Technology Development Fund of Macao SAR (FDCT 0136/2020/A3)
01/2022 – 12/2023	Development and application of a collection of mRNA toolkit strains for visualizing localization and dynamics of membrane-associated genes in C. elegans epithelia, Multi-Year Research Grant of UM (MYRG 2020-00163-FHS)
01/2020 – 12/2021	Establishment of a C. elegans model of HSAN1 disease, Multi-Year Research Grant of UM (MYRG 2019-00063-FHS)
10/2018 – 10/2021	Role of cytoskeleton modulators in apical membrane biogenesis during tubular organ formation, The Science and Technology Development Fund of Macao SAR (FDCT 050/2018/A2)
10/2018 – 10/2021	The mechanistic study on the functional role of a novel ARF-6 effector SAC-1/Sac1p in the regulation of endosomal PI(4,5)P2 level during early endosome to recycling endosome transport, FDCT-MOST joint grant (FDCT 018/2017/AMJ)
01/2018 – 12/2020	Sphingolipidome Analysis in C. elegans, Multi-Year Research Grant of UM (MYRG 2017-00082-FHS)
09/2016 – 08/2019	A role of myosin phosphorylation in microvillus inclusion disease and related syndromes, Multi-Year Research Grant of UM (MYRG 2016-00066-FHS)
01/2016 – 01/2019	RNAi-based screens identify tube morphogenesis genes in the C. elegans gonad systemRNAi, The Science and Technology Development Fund of Macao SAR (FDCT 060/2015/A2)
02/2015 – 02/2018	RNAi screen-based identification of genes functioning in spermatheca morphogenesis in C. elegans, Start-up Research Grant of UM (SRG 2015-00005-FHS)