• Epigenetic studies of DNA methylation in development and disease
• Animal models of human diseases
• Stem cell technology focusing on neural cell differentiation and organoids;
• Development of mRNA delivery technology for treating rare diseases

Guoping Fan is currently a Full Professor at the School of Biomedical Sciences, The University of Hong Kong. He obtained a BSc degree in Biochemistry from Nanjing Univesity and a PhD in Neurosciences from Case Western Reserve University, USA. After completing postdoc training at the Whitehead Institute/MIT in 2001, he was appointed as a faculty member at the Department of Human Genetics, David Geffen School Medicine at University of California Los Angeles (UCLA). At UCLA, he rose to the rank of full Professor in 2011 and has become Professor Emeritus since 2021.  From 2019 to 2024, Professor Fan was also appointed as a distinguished adjunct professor at the ShanghaiTech University, and subsequently became an adjunct professor Scintillon Research Institute in San Diego, California from 2024.  He has published over 120 original papers, reviews and book chapter with citations >25,000. Professor Fan has served as a regular grant reviewer for many agencies including NIH, Maryland, Connecticut, and Pennsylvania States, several Europe countries and Natural Science Foundation of China. He was awarded as a Basil O’Connor Scholar, Carol Moss Spivak Scholar in Neuroscience, Royan International Research Award in Embryology, and a recipient of the First Prize Award in Science and Technology Award from Chinese Medical Society. Professor Fan has been a board member of Chinese Society of Stem Cell Research since 2021.

Our current research focuses on understanding epigenetic mechanisms that regulate neural stem cell differentiation, adult brain function, and somatic cell reprogramming. We utilize advanced molecular and genetic approaches to investigating how DNA cytosine methylation and its associated components, which include methyl-CpG binding proteins and histone modification enzymes, regulate gene expression, cell differentiation and reprogramming, and neural plasticity in mammalian systems.

DNA methylation in development and disease: Abnormal DNA methylation has been associated with several human neurological disorders, including fragile-X, ICF (immunodeficiency, centromere instability, and facial anomaly), and Tatton-Brown-Rahman Syndrome, human overgrowth and dwarfism syndromes. To study the methylation function in the brain, we have used the Cre/loxP conditional gene knockout method to produce transgenic mice that are deficient of the DNA methyltransferases (Dnmts) exclusively in the central nervous system (CNS). More recently, we have used CRSIPR-Cas technology to introduce point mutations in DNMTs to model human diseases in transgenic mice.  Dnmt1 deficiency results in DNA hypomethylation in CNS precursor cells and their progeny neuronal and glial cells. We found that DNA hypomethylation affects neuronal and astroglial differentiation as well as postnatal neuronal survival and maturation in the CNS. We have developed human disease-specific iPSCs to dissect molecular and epigenetic mechanisms underlying these human diseases through directed cell lineage-specific differentiation and organoid development. Understanding epigenetic mechanisms underlying development and disease allows us to devise novel methods to effectively treat human disease through epigenetic gene modifications.

1. Wang J, Deng X, Jian T, Yin S, Chen L, Vergnes L, Li Z, Liu H, Lee R, Lim SY, Bahn JH, Xiao X, Zhu X, Hu G, Reue K, Liu Y, Fan G. DNA methyltransferase 1 modulates mitochondrial function through bridging m5C RNA methylation. Mol Cell. 2025 May 5; doi: 10.1016/j.molcel.2025.04.019. PMID: 40328247

2. Deng X, Fan G. Tuning up gene transcription via direct crosstalk of DNA and RNA methylation.  Mol Cell. 2025 Feb 20;85(4):674-676. doi: 10.1016/j.molcel.2025.01.030. PMID: 39983671

3. Zhang W, Qian S, Chen J, Jian T, Wang X, Zhu X, Dong Y, Fan G 2024  Photo-Crosslinked Pro-Angiogenic Hydrogel Dressing for Wound Healing International Journal of Molecular Sciences 25 (18), 9948

4. Zhang S, Xiao Y, Mo X, Chen X, Zhong J, Chen Z, Liu X, Qiu Y, Dai W, Chen J, Jin X, Fan G, Hu Y. 2024 Simultaneous profiling of RNA isoforms and chromatin accessibility of single cells of human retinal organoids Nature Communications 15 (1), 8022

5. Tian Z, Liu Q, Lin HY, Zhu YR, Ling L, Sung TC, Wang T, Li W, Gao M, Cheng S, Renuka RR, Subbiah SK, Fan G, Wu GJ, Higuchi A. 2024 Effects of ECM protein-coated surfaces on the generation of retinal pigment epithelium cells differentiated from human pluripotent stem cells  Regenerative Biomaterials 11:rbae091. doi: 10.1093/rb/rbae091. PMID: 39233867

6. Xu D, Wan B, Qiu K, Wang Y, Zhang X, Jiao N, Yan E, Wu J, Yu R, Gao S, Du M, Liu C, Li M, Fan G, Yin J. 2023 Single-Cell RNA-Sequencing Provides Insight into Skeletal Muscle Evolution during the Selection of Muscle Characteristics. Adv Sci (Weinh). Dec;10(35):e2305080. doi: 10.1002/advs.202305080.

7. Ma L, Wang F, Li Y, Wang J, Chang Q, Du Y, Sadan J, Zhao Z, Fan G*, Yao B*, Chen JF*. Brain methylome remodeling selectively regulates neuronal activity genes linking to emotional behaviors in mice exposed to maternal immune activation. Nat Commun. 2023 Nov 29;14(1):7829. doi: 10.1038/s41467-023-43497-4.

8. Liu Q, Liu J, Guo M, Sung TC, Wang T, Yu T, Tian Z, Fan G, Wu W, Higuchi A. 2023. Comparison of retinal degeneration treatment with four types of different mesenchymal stem cells, human induced pluripotent stem cells and RPE cells in a rat retinal degeneration model. J Transl Med. 2023 Dec 14;21(1):910. doi: 10.1186/s12967-023-04785-1. PMID: 38098048 Free PMC article.

9. Tian C, Wang J, Ye X, Chen J, Zheng R, Yu H, Li J, Yin G, Liu L, Zhao N, Feng G, Zhu Z, Wang J*, Fan G*, Liu L*. Culture conditions of mouse ESCs impact the tumor appearance in vivo. Cell Rep. 2023 Jun 27;42(6):112645. doi: 10.1016/j.celrep.2023.112645. Epub 2023 Jun 13. PMID: 37314926 Free article.

10.  Deng P, Yuan Q, Cheng Y, Li J, Liu Z, Liu Y, Li Y, Su T, Wang J, Salvo ME, Wang W, Fan G, Lyons K, Yu B, Wang CY. Loss of KDM4B exacerbates bone-fat imbalance and mesenchymal stromal cell exhaustion in skeletal aging.Cell Stem Cell. 2021 Jun 3;28(6):1057-1073.e7. doi: 10.1016/j.stem.2021.01.010. Epub 2021 Feb 10. PMID: 33571444

11. Wei Y, Zhang C, Fan G, Meng L. Organoids as Novel Models for Embryo Implantation Study.Reprod Sci. 2021 Jun;28(6):1637-1643. doi: 10.1007/s43032-021-00501-w. Epub 2021 Mar 1. PMID: 33650092 Review.

12. Jansova D, Aleshkina D, Jindrova A, Iyyappan R, An Q, Fan G, Susor A. Single Molecule RNA Localization and Translation in the Mammalian Oocyte and Embryo. J Mol Biol. 2021 Sep 17;433(19):167166. doi: 10.1016/j.jmb.2021.167166. Epub 2021 Jul 20. PMID: 34293340.

13. Song Y, Soto J, Wang P, An Q, Zhang X, Hong S, Lee LP, Fan G, Yang L, Li S. Asymmetric Cell Division of Fibroblasts is An Early Deterministic Step to Generate Elite Cells during Cell Reprogramming.Adv Sci (Weinh). 2021 Feb 25;8(7):2003516. doi: 10.1002/advs.202003516. eCollection 2021 Apr. PMID: 33854891

14. He D, Wang D, Lu P, Yang N, Xue Z, Zhu X, Zhang P, Fan G. Single-cell RNA sequencing reveals heterogeneous tumor and immune cell populations in early-stage lung adenocarcinomas harboring EGFR mutations. Oncogene. 2021 Jan;40(2):355-368. doi: 10.1038/s41388-020-01528-0.

15. Lu P, Yang G, Jiang L, He W, Wu W, Qi L, Shen S, Rao J, Zhang P, Xue Z, Jiang C, Fan G*, Zhu X*. Characterizing disease progression of nonalcoholic steatohepatitis in Leptin-deficient rats by integrated transcriptome analysis. Exp Biol Med (Maywood). 2020 Dec 10:1535370220976530. doi: 10.1177/1535370220976530.

16. Lv B, An Q, Zeng, Q, Zhang X, Lu P, Wang Y, Zhu X, Ji Y*, Fan G*, Xue Z* 2019.  Single-cell RNA sequencing reveals regulatory mechanism for trophoblast cell-fate divergence in human peri-implantation conceptuses. PLoS biology 17 (10), e3000187

17. Mao X, An Q, Xi H, Yuan S, Yang X, Wang J, Hu Y, Liu Q, Fan G*. Single cell RNA sequencing of hESC-derived 3D retinal organoids reveals novel genes regulating RPC commitment in early human retinogenesis. Stem Cell Reports. 2019 Sep 11. pii: S2213-6711(19)30306-6. doi: 10.1016/j.stemcr.2019.08.012. PMID: 31543471

18. Hu Y, K Huang, Q An, G Du, G Hu, J Xue, X Zhu, CY Wang, Z Xue, G Fan*. 2016.  Simultaneous profiling of transcriptome and DNA methylome from a single cell. Genome Biology  17(1):88. published May 5th 2016.

19. Huang K, Maruyama T,  Fan G. (2014) The naive state of human pluripotent stem cells: A synthesis of stem cell and premiplantation embryo transcriptome analyses. Cell Stem Cell 15(4):410-5.

20. Huang K, Wu Z, Liu Z, Hu G, Yu J, Chang KH, Kim KP, Le T, Faull KF, Rao N, Gennery A, Xue Z, Wang CY, Pellegrini M, Fan G. (2014).  Selective demethylation and altered gene expression in human induced pluripotent stem cells and mesenchymal stem cells associated with ICF Syndrome.  Human Molecular Genetics  23(24):6448-57. doi: 10.1093/hmg/ddu365. Epub 2014 Jul 15.

21. Huang K, Shen Y, Bibikova M, April C, Wang AY, Cheng LZ, Nagy A, Pellegrini M, Fan JB, Fan G. (2013) A panel of CG methylation sites distinguishes human embryonic stem cells and induced pluripotent stem cells.  Stem Cell Reports (published online 12/26/2013).

22. Xue Z, Huang K, Cai C, Cai L, Jiang C-Y, Feng Y, Liu Z, Cheng L, Sun YE, Liu J-Y,  Horvath S, and Fan G (2013). Genetic Programs in Human and Mouse Early Embryos Revealed by Single-Cell RNA-Sequencing.  Nature  500(7464):593-7. doi: 10.1038/nature12364. Epub 2013 Jul 28.

23. Feng, J., Zhou, Y.,  Campbell, S., Le, T., Li, E., Sweatt, J.D., Silva, A.J. and  Fan, G.  (2010)  Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons.  Nature Neuroscience V13, 423-430. 

24. Liao JL, Yu J, Huang K, Hu J, Diemer T, Ma Z, Dvash T, Yang XJ, Travis GH, Williams DS, Bok D, Fan G. 2010. Molecular Signature of Primary Retinal Pigment Epithelium and Stem-Cell derived RPE cells.  Hum Mol Genet. 19(21):4229-38.  Online version on Aug 13.

25. Shen, Y., Chow, J., Wang, Z., Fan, G.  (2006).  Abnormal CpG island methylation occurs during in vitro differentiation of human embryonic stem cells.  Human Molecular Genetics.  15: 2623-2635.

26. Fan, G.*, Martinowich, K., Chin, M., He, F., Fouse, S., Hutnick, D., Hattori, D.,  Ge, W., Shen, Y., Wu, H., ten Hoeve, T., Shuai,  K.,  and Sun, Y*. (*Corresponding authors). (2005).  DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling.  Development. 132: 3345-56.

27. Martinowich, K., Hatorri, D., Wu, H., Fouse, S., He, F., Hu, Y., Fan, G*., Sun, Y*. (*Corresponding authors) (2003). DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation.  Science 302, 890-893.

28. Fan, G., Beard, C., Chen, R., Csankovszki, G., Sun, Y., Siniaia, M., Bates, B., Lee, P., Trumpp, A., Poon, C., Wilson, C., and Jaenisch, R. (2001) DNA hypomethylation perturbs  the function and survival of CNS neurons in postnatal animals.   J. Neurosci. 21, 788-797.           

29. Fan, G., Egles, C., Sun, Y., Minichiello, L., Renger, J., Klein, R., Liu, G., and Jaenisch, R.  (2000)  Knocking the NT4 gene into the BDNF locus rescues BDNF deficient mice and reveals distinct NT4 and BDNF activities. Nature Neurosci. 3, 350-357.

• We are seeking a highly motivated and talented Postdoctoral Researcher to join our team in the University of Hong Kong, focusing on cutting-edge research in stem cell biology and epigenetics studies. The successful candidate will work on innovative projects exploring stem cell differentiation, gene regulation, regenerative medicine, and therapeutic applications, contributing to advancements in biomedical science.

• The role of DNA methylation in development and disease
• Mouse models of neurodegeneration
• RNA modifications and delivery in cells and animal models
• Epigenetic mechanisms of ageing and anti-ageing