Professor Hongyuan (Robert) Yang
Education
- Bachelor of Medicine (1993), Peking University Health Science Centre, Beijing, China
- PhD (1998), Columbia University, New York, USA
Professional Experience
- 2022-: NHMRC Investigator L3
- 2014-2019: NHMRC Senior Research Fellow B锘
- 2013-current: Professor, School of BABS
- 2010-2013: Inaugural ARC Future Fellow
- 2009-2012: Associate Professor, School of BABS
- 2007-2008: Senior Lecturer, School of BABS, UNSW
- 1999-2007: Lecturer/Assistant Professor/Associate Professor with tenure, Department of Biochemistry, National University of Singapore
- 1999 (April-July): Visiting Fellow, Harvard University锘
- this article on Rob's career by The Journal of Cell Biology听
Research Program and Contribution
Our long-term research interests focus on two fundamental yet emerging areas in cell and medical biology:
1.听 Intracellular lipid (e.g., cholesterol and phosphatidylserine) sorting/transport, and its role in cancer, heart and neurodegenerative diseases.
2.听 The biogenesis and dynamics of lipid droplets, adipocyte development, obesity and diabetes.
These two areas are closely linked because lipid droplets may play a crucial role in cellular lipid听transport, and lipid droplets are a primary storage site for both free and esterified cholesterol.
Cellular lipid听trafficking is a difficult subject to study given the lack of effective approaches to label lipids in live cells. However, it is an important cell biological question because lipids are actively sorted and transported in all eukaryotic cells. In addition, many human diseases such as atherosclerosis, Alzheimer鈥檚 and cancer听are linked to aberrant lipid听transport.
My early work led to the identification of two key enzymes that catalyze sterol esterification, an important homeostatic step for storing excess sterols (Yang et al., Science, 1996). Our laboratory subsequently identified novel molecules and schemes that govern cellular lipid听transport (Wang et al., EMBO J, 2005; Du et al, J Cell Biol., 2011;听Ghai et al, Nature Communications, 2017; Dong et al., Nat Comms, 2019; Wang et al., Molecular Cell, 2019;听Du et al., JCB, 2020; Qian et al., Cell, 2020). Currently we aim to identify and characterize novel proteins that regulate the trafficking of cholesterol or phosphatidylserine between cellular organelles.
Lipid droplets are key cellular organelles that regulate energy storage and metabolism.听 We have identified a number of factors that impact the size of lipid droplets (Fei et al, J Cell Biol., 2008;听Fei et al, PLoS Genetics, 2011). One such protein, seipin, also plays an important role in human adipocyte development and maintenance (Cui et al., Human Mol Gen., 2011; Liu et al, Diabetes, 2014; Pagac et al, Cell Reports, 2016; Yan et al, Developmental Cell, 2018). Currently, we aim to understand how lipid droplets are formed from the ER and the exact role of seipin in this process.
Honours and Awards
- NHMRC Investigator L3 (2022-2027)
- UNSW Dean of Science Research Excellence Award (2019)
- NHMRC Senior Research Fellowship B (2014-2019)
- Inaugural ARC Future Fellowship (2010-2014)
- Yong Loo Lin School of Medicine Research Excellence Young Scientist Award (2006)
- Finalist, Singapore National Young Scientist Award (2005)
- National University of Singapore (NUS) Technopreneurship 21 Award (2004)
- National University of Singapore (NUS) Young Scientist Award (2002)
Editorial Service
- Member of听Editorial Board/Academic Editor, Journal of Cell Biology听
- Member of听Editorial Board, BBA-Molecular Cell Biology of Lipids
Selected Publications
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Liu Y. and听Yang H. (2024) WIPI4 loss linked to ferroptosis.听Nature Cell Biol., 26: 506-507
Li YE, Norris DM, Xiao FN, Pandzic E, Whan RM, Fok S, Zhou M, Du G, Liu Y, Du X,听Yang H. (2024) Phosphatidylserine regulates plasma membrane repair through tetraspanin-enriched macrodomains.听J Cell Biol; 223: e202307041.
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
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. 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. (2021)听AGPAT2 interaction with CDP-diacylglycerol synthases promotes the flux of fatty acids through the CDP-diacylglycerol pathway.听Nature Communications. 12(1):6877. doi: 10.1038/s41467-021-27279-4.
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. Highlighted by Faculty Opinions听https://facultyopinions.com/prime/740025624#tab=recommendations听
Yan R., Cao P., Song W., Qian H., Du X., Coates H.W., Zhao X., Li Y., Gao S., Gong X., Liu X., Sui J., Lei J., Yang H., Brown A.J., Zhou Q., Yan C. and Yan N. (2021) A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols. SCIENCE, 371(6533):eabb2224.听doi:10.1126/science.abb2224.听
Du X. and Yang H. (2021) Seipin regulates the formation of nuclear lipid droplets from a distance. Journal of Cell Biology; 220 (1): e202011166.
Qian H., Wu X., Du X., Yao X., Zhao X., Lee J., Yang H*, and Yan N*. (2020) Structural basis of low pH-dependent lysosomal cholesterol egress by NPC1 and NPC2. CELL, 182: 1-14.听 * Co-corresponding authors.
Gao M., Liu L., Wang X., Mak H.Y., Liu G. and Yang H. (2020) GPAT3 deficiency alleviates insulin resistance and hepatic steatosis in a mouse model of severe congenital generalized lipodystrophy. Human Molecular Genetics. 1; 29: 432-443.
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,听219, 1-16.听
Qian H., Zhao X., Yan R., Gao S., Sun X., Du X., Yang H., Wong CCL. and Yan N. (2020) Structural basis for catalysis and substrate specificity of human ACAT1. NATURE, 581: 333-338.
Luo J., Yang H. and Song B.L. (2020) Nature Reviews Molecular Cell Biology.听21(4): 225-245.听
Wang H., Ma, Q., Qi, Y., Dong, J., Du, X., Rae, J., Brown A.J., Parton R.G., Wu J.W. and Yang H. (2019)听ORP2 delivers cholesterol to the plasma membrane in exchange for phosphatidylinositol 4, 5-bisphosphate (PI(4,5)P2).听Molecular Cell,听73, 1鈥16. Cover Story.听
Gao听M., Huang X., Song听B.L. and Yang H. (2019) Progress in Lipid Research, 75: 100989. published online July 24th.
Dong J., Du X., Wang H., Wang J., Lu C., Chen X., Zhu Z., Luo Z., Yu L., Brown A.J.,听Yang H* and Wu JW*. (2019)听Allosteric enhancement of ORP1-mediated cholesterol transport by PI(4,5)P2/PI(3,4)P2.听Nature Communications, 10: 829. * co-corresponding authors.锘刻
Xu Y., Du X., Turner N., Brown AJ and Yang H. (2019) Enhanced acyl-CoA: cholesterol acyltransferase activity increases cholesterol levels on lipid droplet surface and impairs adipocyte function. Journal of Biological Chemistry, 294: 19306-19321.
Xu Y., Mak H.Y., Lukmantara I., Li Y.E., Hoehn K.L., Huang X., Du X. and Yang H. (2019) CDP-DAG Synthase 1 and 2 regulate lipid droplet growth through distinct mechanisms. Journal of Biological Chemistry, 294, 1-16;听doi:10.1074/jbc.RA119.009992
Gao M. and Yang H. (2018)听VPS13: A lipid transfer protein making contacts at multiple cellular locations.听 Journal of Cell Biology,听217: 3322-3324.听听锘匡豢
Yan R., Qian H., Lukmantara I., Gao M., Du, X., Yan N. and Yang H. (2018)听Human SEIPIN Binds Anionic Phospholipids.听Developmental Cell, 47, 1鈥9.
Du X, Zadoorian A, Lukmantara I, Qi Y, Brown AJ & Yang H. (2018)听Oxysterol-binding protein-related protein 5 (ORP5) promotes cell proliferation by activation of mTORC1 signaling.听Journal of Biological Chemistry, 293: 3806-3818.
Du X, Turner N & Yang H. (2018)听The role of oxysterol binding proteins in cancer.听Seminars in Cell and Developmental Biology, 81: 149-153.
Ghai R, Du X, Wang H, Dong J, Ferguson C, Brown AJ, Parton RG, Wu JW & Yang H. (2017)听 ORP5 and ORP8 bind phosphatidylinositol-4, 5-biphosphate (PtdIns(4,5)P2) and regulate its level at the plasma membrane.听Nature Communications,听8:757.听
Qi Y, Kapterian TS, Du X, Ma Q, Fei W, Zhang Y, Huang X, Dawes IW & Yang H. (2016).听CDP-diacylglycerol synthases regulate the growth of lipid droplets and adipocyte development.听Journal of Lipid Research, 57:767-80.
Pagac M, Cooper DE, Qi Y, Lukmantara IE, Mak HY, Wu Z, Tian Y, Liu Z, Lei M, Du X, Ferguson C, Kotevski D, Sadowski P, Chen W, Boroda S, Harris TE, Liu G, Parton RG, Huang X, Coleman RA & Yang H. (2016)听SEIPIN regulates lipid droplet expansion and adipocyte development through modulating the activity of glycerol-3-phosphate acyltransferase.听Cell Reports, 17: 1546鈥1559.锘
Chu BB, Liao YC, Qi W, Xie C, Du X, Wang J, Yang H, Miao HH, Li BL & Song BL. (2015)听Cholesterol transport through a lysosome-peroxisome membrane contact.听CELL, 161: 291-306.
Du X, Brown AJ & Yang H. (2015).听Novel mechanisms of intracellular cholesterol transport: membrane contact sites and oxysterol binding proteins.听Current Opinion in Cell Biology, 35; 37-42.锘
Liu L, Jiang QQ, Wang, X, Zhang Y, Lin RC, Lan S, Shui, G, Zhou L, Li P, Wang Y, Cui X, Gao MM, Zhang L, Lv Y, Xu G, Liu G, Zhao D & Yang H. (2014)听Adipose-specific knockout of seipin/BSCL2 results in progressive lipodystrophy.听Diabetes,听63:1鈥12 doi 10.2337/db13-0729
Du X, Kazim AS, Dawes IW, Brown AJ & Yang H. (2013)听The AAA ATPase VPS4/SKD1 Regulates Endosomal Cholesterol Trafficking Independently of ESCRT-III.听Traffic,听14: 107-19.
Yang H*, Galea A, Sytnyk V & Crossley M. (2012)听Controlling the size of lipid droplets: protein and lipid factors.听Current Opinion in Cell Biology,听24:509-16. (* corresponding author)
Cui X, Wang Y, Meng L, Fei W, Deng J, Xu G, Peng X, Ju S, Liu G, Zhao L & Yang H. (2012)听Overexpression of a short isoform of human seipin/BSCL2 in mouse adipose tissue results in mild lipodystrophy.听Am J Physiol Endocrinol Metab,听302: E705-13.
Du X, Kazim A, Brown AJ & Yang H. (2012)听An essential role of Hrs/Vps27 in endosomal cholesterol trafficking.听Cell Reports, 1: 29-35. (Inaugural Issue)
Fei W, Shui G, Zhang Y, Krahmer N, Ferguson C, Kapterian TS, Lin RC, Dawes IW, Brown AJ, Li P, Huang X, Parton RG, Wenk MR, Walther TC & Yang H. (2011)听
A role for phosphatidic acid in the formation of 鈥渟upersized鈥 lipid droplets.听PLoS Genetics, 7: e1002201.
Cui X, Wang Y, Tang Y, Liu Y, Zhao L, Deng J, Xu G, Peng X, Ju S, Liu, G & Yang H. (2011)听Seipin ablation in mice results in severe generalized lipodystrophy.听Human Molecular Genetics, 20: 3022-30
Fei W, Du X & Yang H. (2011)听Seipin, adipogenesis and lipid droplets.听Trends in Endocrinology and Metabolism, 22: 204-10.
Du X, Kumar J, Ferguson C, Schulz TA, Ong YS, Hong W, Prinz WA, Parton RG, Brown AJ & Yang H. (2011)听A role for oxysterol-binding protein-related protein 5 in endosomal cholesterol trafficking.听Journal of Cell Biology, 192: 121-135.
Fei W, Wang H, Fu X, Bielby C & Yang H. (2009)听Conditions of endoplasmic reticulum stress stimulate lipid droplet formation in Saccharomyces cerevisiae.听Biochemical Journal听424:61-7.
Low CP, Shui GH, Liew LP, Buttner S, Madeo F, Dawes IW, Wenk MR & Yang H. (2008)听Caspase-dependent and -independent lipotoxic cell-death pathways in fission yeast. Journal of Cell Science, 121:听 2671-2684. Editorial highlight听by JCS
Fei W, Shui G, Gaeta B, Du X, Kuerschner L, Li P, Brown AJ, Wenk MR, Parton RG & Yang H. (2008)听Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast. Journal of Cell Biology,听180: 473-482. Highlighted by BioCentury Science Business Xchange
Yang H. (2006)听Nonvesicular sterol transport: two protein families and a sterol sensor?听Trends Cell Biol. 16: 427-32. Epub 2006 Jul 28.
Wang P, Zhang Y, Li H, Chieu HK, Munn AL & Yang H. (2005)听AAA ATPases regulate membrane association of yeast oxysterol binding proteins and cellular sterol metabolism.听EMBO Journal,听24: 2989-99
Zhang Q, Chieu HK, Low CP, Zhang S, Heng CK & Yang H. (2003)听Schizosaccharomyces pombe cells deficient in triacylglycerols synthesis undergo apoptosis upon entry into the stationary phase.听Journal of Biological Chemistry, 278: 47145-55
Yang H, Bard M, Bruner DA, Gleeson A, Deckelbaum RJ, Aljinovic G, Pohl T, Rothstein R & Sturley SL. (1996)听Sterol Esterification in Yeast: A two gene process.听Science, 272, 1353-1356.
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My Research Supervision
In 2021, there will be two听Ph.D. students and three honors students