Dr Robin Du
2003 鈥� 2007: PhD in Biochemistry and Molecular Genetics, 91色情片
2002 鈥� 2003: MSc in Biotechnology, 91色情片
Professional Experience:
2010 鈥� current: Senior Research Associate, School of BABS
2007 鈥� 2010: Postdoctoral Research Fellow, School of BABS
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Research Contribution:
Dr Du鈥檚 research focuses on understanding the molecular mechanisms of intracellular lipid trafficking and investigating how changes in membrane lipid distribution and metabolism contribute to metabolic disorders and cancer. He received a PhD from 91色情片 in 2007 for studies examining molecular machinery controlling cholesterol homeostasis and cell signalling. After his PhD training, Dr Du continued to investigate molecular functions of lipid transfer proteins, such as Niemann Pick Type C proteins and oxysterol-binding protein-related proteins. He has since developed a keen interest in intracellular lipid trafficking and its role in human diseases. He has gained further extensive experience in genetics, molecular cloning, genome editing, protein purification, lipidomics, advanced fluorescent microscopy, and new model systems such as yeast and mouse. In 2010, Dr Du became a Senior Research Associate. He is currently leading a research team focusing on organellar membrane lipid dynamics mediated by lipid transfer proteins at the School of BABS, 91色情片.
Dr Du has a record of continuing publications in high-profile, peer-reviewed journals, including Cell, Nature, Science, Molecular Cell, Nature Communications, Developmental Cell, Cell Reports, Journal of Cell Biology, Journal of Lipid Research, Molecular Biology of the Cell, and Journal of Biological Chemistry. Dr Du serves as a referee for the NHMRC and a reviewer for the International Journal of Cell Biology, PLOS ONE and others. He is also an active member of the ASBMB and Biochemical Society (London).
Dr Du鈥檚 publications and citations can be found at:听
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Selected Publications:
Zadoorian A, Du听X and Yang H. (2023)听Lipid droplet biogenesis and functions in health and disease.听Nature Reviews Endocrinology.听https://doi.org/10.1038/s41574-023-00845-0听()
Coates HW, Capell-Hattam IM, Olzomer EM,听Du X, Farrell R, Yang H, Byrne FL, Brown AJ. (2023)听Hypoxia truncates and constitutively activates the key cholesterol synthesis enzyme squalene monooxygenase. eLife.听Jan 19;12:e82843. doi: 10.7554/eLife.82843. ()
Keable R, Hu S, Pfundstein G, Kozlova I, Su F,听Du X, Yang H, Gunnersen J, Schachner M, Leshchyns'ka I, Sytnyk V. (2022)听The BACE1-generated C-terminal fragment of the neural cell adhesion molecule 2 (NCAM2) promotes BACE1 targeting to Rab11-positive endosomes.听Cellular and Molecular Life Sciences.听Oct 17;79(11):555. doi: 10.1007/s00018-022-04575-w. ()
Lukmantara I, Chen F, Mak HY, Zadoorian A, Du X, Xiao FN, Norris DM, Pandzic E, Whan R, Zhong Q and Yang H. (2022) PI(3)P and DFCP1 regulate the biogenesis of lipid droplets.听Mol Biol Cell. 33(14):ar131. ()
Mak HY, Ouyang Q, Tumanov S, Xu J, Rong P, Dong F, Lam SM, Wang X, Lukmantara I, Du X, Gao M, Brown AJ, Gong X, Shui G, Stocker R, Huang X, Chen S and听Yang H.听(2021)听AGPAT2 interaction with CDP-diacylglycerol synthases promotes the flux of fatty acids through the CDP-diacylglycerol pathway.听Nature Communications.听12(1):6877. doi: 10.1038/s41467-021-27279-4. ()
Zhang T, Li YE, Yuan Y, Du X, Wang Y, Dong X, Yang H, Qi S. TMEM41B and VMP1 are phospholipid scramblases. Autophagy 1-3 12 Jun 2021 ()
Li YE*, Wang Y*, Du X*, Zhang T, Mak HY, Hancock SE, McEwen H, Pandzic E, Whan RM, Aw YC, Lukmantara IE, Yuan Y, Dong X, Don A, Turner N, Qi S and听Yang H. (2021)听听TMEM41B and VMP1 are scramblases and regulate the distribution of cholesterol and phosphatidylserine.听Journal of Cell Biology; 220 (6),听e202103105(*co-first) ()
Yan R, Cao P, Song W, Qian H, Du X, Coates HW, Zhao X, Li Y, Gao S, Gong X, Liu X, Sui J, Lei J, Yang H, Brown AJ, Zhou Q, Yan C, Yan N. (2021)听A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols. Science听Jan 14:eabb2224. doi: 10.1126/science.abb2224. ()
Du, X., Yang, H. (2021) Seipin regulates the formation of nuclear lipid droplets from a distance.听 Journal of Cell Biology Jan 4;220(1):e202011166. doi: 10.1083/jcb.202011166. ()
Qian, H.*, Wu, X.*, Du, X.*, Yao, X., Zaho, X., Yang, H., and Yan, N. (2020) Structural basis of low pH-dependent lysosomal cholesterol egress by NPC1 and NPC2. Cell听182, 1-14听(*co-first) ()
Qian, H., Zhao, X., Yan, R., Yao, X., Gao, S., Sun, X., Du, X., Yang, H., Wong, C. C. L., and Yan, N. (2020) Structural basis for catalysis and substrate specificity of human ACAT1. Nature 581, 333-338 ()
Du, X.*, Zhou, L., Aw, Y. C., Mak, H. Y., Xu, Y., Rae, J., Wang, W., Zadoorian, A., Hancock, S. E., Osborne, B., Chen, X., Wu, J. W., Turner, N., Parton, R. G., Li, P., and Yang, H.* (2020) ORP5 localizes to ER-lipid droplet contacts and regulates the level of PI(4)P on lipid droplets. Journal of Cell Biology 219 (*co-corresponding) ()听
Wang, H., Ma, Q., Qi, Y., Dong, J., Du, X., Rae, J., Wang, J., Wu, W. F., Brown, A. J., Parton, R. G., Wu, J. W., and Yang, H. (2019) ORP2 Delivers Cholesterol to the Plasma Membrane in Exchange for Phosphatidylinositol 4, 5-Bisphosphate (PI(4,5)P2). Molecular Cell 73, 458-473 e457 ()听
Dong, J.*, Du, X.*, Wang, H.*, Wang, J., Lu, C., Chen, X., Zhu, Z., Luo, Z., Yu, L., Brown, A. J., Yang, H., and Wu, J. W. (2019) Allosteric enhancement of ORP1-mediated cholesterol transport by PI(4,5)P2/PI(3,4)P2. Nature Communications 10, 829 (*co-first) ()
Yan, R., Qian, H., Lukmantara, I., Gao, M., Du, X., Yan, N., and Yang, H. (2018) Human SEIPIN Binds Anionic Phospholipids. Developmental Cell 47, 248-256 e244 ()听
Du, X.*, Zadoorian, A., Lukmantara, I. E., Qi, Y., Brown, A. J., and Yang, H.* (2018) Oxysterol-binding protein-related protein 5 (ORP5) promotes cell proliferation by activation of mTORC1 signaling. Journal of Biological Chemistry 293, 3806-3818 (*co-corresponding) ()
Du, X., Turner, N., and Yang, H. (2018) The role of oxysterol-binding protein and its related proteins in cancer. Seminars in Cell and Developmental Biology 81, 149-153 ()
Ghai, R.*, Du, X.*, Wang, H., Dong, J., Ferguson, C., Brown, A. J., Parton, R. G., Wu, J. W., and Yang, H. (2017) ORP5 and ORP8 bind phosphatidylinositol-4, 5-biphosphate (PtdIns(4,5)P 2) and regulate its level at the plasma membrane. Nature Communications 8, 757 (*co-first) ()
Pagac, M., Cooper, D. E., Qi, Y., Lukmantara, I. E., Mak, H. Y., Wu, Z., Tian, Y., Liu, Z., Lei, M., Du, X., Ferguson, C., Kotevski, D., Sadowski, P., Chen, W., Boroda, S., Harris, T. E., Liu, G., Parton, R. G., Huang, X., Coleman, R. A., and Yang, H. (2016) SEIPIN Regulates Lipid Droplet Expansion and Adipocyte Development by Modulating the Activity of Glycerol-3-phosphate Acyltransferase. Cell Reports 17, 1546-1559 ()
Du, X.*, Zhang, Y., Jo, S. R., Liu, X., Qi, Y., Osborne, B., Byrne, F. L., Smith, G. C., Turner, N., Hoehn, K. L., Brown, A. J., and Yang, H.* (2015) Akt activation increases cellular cholesterol by promoting the proteasomal degradation of Niemann-Pick C1. Biochemical Journal 471, 243-253 (*co-corresponding) ()
Du, X., Brown, A. J., and Yang, H. (2015) Novel mechanisms of intracellular cholesterol transport: oxysterol-binding proteins and membrane contact sites. Current Opinion in Cell Biology 35, 37-42 ()
Chu, B. B., Liao, Y. C., Qi, W., Xie, C., Du, X., Wang, J., Yang, H., Miao, H. H., Li, B. L., and Song, B. L. (2015) Cholesterol transport through lysosome-peroxisome membrane contacts. Cell 161, 291-306 ()
Du, X., Kazim, A. S., Dawes, I. W., Brown, A. J., and Yang, H. (2013) The AAA ATPase VPS4/SKD1 regulates endosomal cholesterol trafficking independently of ESCRT-III. Traffic 14, 107-119 ()听
Du, X., Kazim, A. S., Brown, A. J., and Yang, H. (2012) An essential role of Hrs/Vps27 in endosomal cholesterol trafficking. Cell Reports 1, 29-35 ()
Du, X., Kumar, J., Ferguson, C., Schulz, T. A., Ong, Y. S., Hong, W., Prinz, W. A., Parton, R. G., Brown, A. J., and Yang, H. (2011) A role for oxysterol-binding protein-related protein 5 in endosomal cholesterol trafficking. Journal of Cell Biology 192, 121-135 ()
Fei, W., Shui, G., Gaeta, B., Du, X., Kuerschner, L., Li, P., Brown, A. J., Wenk, M. R., Parton, R. G., and Yang, H. (2008) Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast. Journal of Cell Biology 180, 473-482 ()
Du, X., Kristiana, I., Wong, J., and Brown, A. J. (2006) Involvement of Akt in ER-to-Golgi transport of SCAP/SREBP: a link between a key cell proliferative pathway and membrane synthesis. Molecular Biology of Cell 17, 2735-2745 ()
Du, X., Pham, Y. H., and Brown, A. J. (2004) Effects of 25-hydroxycholesterol on cholesterol esterification and sterol regulatory element-binding protein processing are dissociable: implications for cholesterol movement to the regulatory pool in the endoplasmic reticulum. Journal of Biological Chemistry 279, 47010-47016 ()
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- Publications
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- Engagement
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2019, Research Excellence Awards, Australian Association of Chinese Biomedical Scientists
2020, Research Excellence Awards, Australian Association of Chinese Biomedical Scientists
RESEARCH INTERESTS
1.听 Intracellular lipid (e.g., cholesterol and phosphatidylserine) sorting/transport/scrambling by lipid bind/transfer proteins and scramblases
2.听The role of membrane lipid distribution in cancer and neurodegenerative diseases.
3. The biology of lipid droplets and their associated proteins.听
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RESEARCH ACHIEVEMENTS听
My research has contributed to the significant advance of knowledge in the field of intracellular lipid sensing, trafficking, and storage. My previous work demonstrated that:
- newly identified phospholipid scramblases TMEM41B and VMP1 regulate the intracellular distribution of phosphatidylserine (PS), the focus of this project ().
- lysosomal cholesterol egress requires low-pH-dependent structural alteration of NPC1 and NPC2 ().
- lipid transfer protein ORP5 can connect the endoplasmic reticulum to lipid droplet and maintain the abundance of lipids on the lipid droplet surface ().
- lipid transfer proteins, including ORP1, ORP5 and ORP8, can exchange lipids between two organelles at membrane contact sites (; ).
- lipid transfer proteins such as NPC1 and ORP5 can be associated with cell signalling and play a role in cancer development (; ).
- lysosomal low-density lipoprotein-derived cholesterol transport involves endoplasmic reticulum-anchored lipid transfer proteins (ORP5) and the components (Hrs and VPS4) of the ESCRT (endosomal sorting complex required for transport) pathway (; ; ).
- processing of SREBP (sterol-responsive element binding protein), the transcription factor that governs cholesterol synthesis and uptake, is regulated by an important signalling molecule (Akt), linking a key cell proliferative pathway to membrane synthesis ().
- effects of an oxysterol (25-hydroxycholesterol) on cholesterol esterification and cholesterol sensing by its homeostatic machinery are dissociable, providing the first insight into the measurement of cholesterol transport to the endoplasmic reticulum ().