695 Charles Young Drive South
Los Angeles, CA 90095 Room 6357C, Gonda Building
Campus - 708822
CA 695 Charles Young Drive South
Los Angeles, CA 90095
Office Phone Number:
Member, Bioinformatics GPB Home Area, Brain Research Institute, Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, Gene Regulation GPB Home Area, Genetics & Genomics GPB Home Area, JCCC Gene Regulation Program Area, Neuroscience GPB Home Area
Our current research focuses on understanding epigenetic mechanisms that regulate neural stem cell differentiation, adult brain function, and somatic cell reprogramming. We utilize 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. 1). DNA methylation in neural development and function: Abnormal DNA methylation has been associated with several human mental retardation disorders, including fragile-X, ICF(immunodeficiency, centromere instability, and facial anomaly), and Rett 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 methyltransferase I (Dnmt1) exclusively in the central nervous system (CNS). 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 are currently defining the molecular mechanism by which DNA hypomethylation alters neuronal gene expression (Science 302: 890-893), cell survival, and lineage-differentiation in the CNS (Human Molecular Genetics 18:2875-2888). 2). Epigenetic mechanisms underlying stem cell regulation, reprogramming, and human diseases The recent breakthrough of reprogramming somatic cells into induced pluripotent stem cells (iPSCs) also provides us with a unique opportunity to model human genetic disorders in stem cells. One of the focuses in our lab is to establish human iPSCs carrying genetic mutations leading to human diseases such as Fragile-X and ICF Syndrome. These human disease-specific iPSCs will be powerful model systems to dissect molecular and epigenetic mechanisms underlying these human diseases. Our second focus is to study how genome-wide DNA methylation is regulated in cell reprogramming. Both embryonic stem (ES) cells and induced pluripotent stem cells (iPSCs) can be induced to differentiate into multiple somatic cell lineages in vitro. However, mechanisms underlying directed differentiation of pluripotent stem cells are poorly understood. To examine whether cell lineage-specific differentiation of stem cells is regulated by epigenetic factors such as DNA methylation and histone modifications, we have established a culture system to induce sequential neural lineage differentiation with both mouse and human ESCs and iPSCs. Understanding epigenetic mechanisms underlying stem cell differentiation allows us to devise and standardize methods to convert pluripotent stem cells into neural precursor cells and specific types of neurons for neural repair.
Guoping Fan is a Professor in the Department of Human Genetics, David Geffen School of Medicine at UCLA. He has been a faculty member at UCLA since 2001. Pior to that, he was a postdoctoral fellow at the Whitehead Institute for Biomedical Institute/MIT, where he studies the role of DNA methylation and neurotrophins in neural development. Dr. Fan earned his B.S. in Biochemistry at Nanjing University, China and Ph.D. in Neuroscience at Case Western Reserve University. His current research focuses on the actions of DNA methylation and chromatin-remodeling in regulating neural gene expression, neuronal function, and stem cell differentiation and reprogramming.
A selected list of publications:
- Moore Lisa D, Le Thuc, Fan Guoping DNA methylation and its basic function Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013; 38(1): 23-38.
- Xue Zhigang, Huang Kevin, Cai Chaochao, Cai Lingbo, Jiang Chun-yan, Feng Yun, Liu Zhenshan, Zeng Qiao, Cheng Liming, Sun Yi E, Liu Jia-yin, Horvath Steve, Fan Guoping Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing Nature, 2013; 500(7464): 593-7.
- Chen Yinyin, Huang Kevin, Nakatsu Martin N, Xue Zhigang, Deng Sophie X, Fan Guoping Identification of novel molecular markers through transcriptomic analysis in human fetal and adult corneal endothelial cells Human molecular genetics, 2013; 22(7): 1271-9.
- Vincent John J, Huang Yun, Chen Pao-Yang, Feng Suhua, CalvopiÃ±a Joseph H, Nee Kevin, Lee Serena A, Le Thuc, Yoon Alexander J, Faull Kym, Fan Guoping, Rao Anjana, Jacobsen Steven E, Pellegrini Matteo, Clark Amander T Stage-specific roles for tet1 and tet2 in DNA demethylation in primordial germ cells Cell stem cell, 2013; 12(4): 470-8.
- Wu Zhourui, Huang Kevin, Yu Juehua, Le Thuc, Namihira Masakasu, Liu Yupeng, Zhang Jun, Xue Zhigang, Cheng Liming, Fan Guoping Dnmt3a regulates both proliferation and differentiation of mouse neural stem cells Journal of neuroscience research, 2012; 90(10): 1883-91.
- Hu Ganlu, Huang Kevin, Yu Juehua, Gopalakrishna-Pillai Sailesh, Kong Jun, Xu He, Liu Zhenshan, Zhang Kunshan, Xu Jun, Luo Yuping, Li Siguang, Sun Yi E, Iverson Linda E, Xue Zhigang, Fan Guoping Identification of miRNA signatures during the differentiation of hESCs into retinal pigment epithelial cells PloS one, 2012; 7(7): e37224.
- Cushman Jesse D, Maldonado Jose, Kwon Eunice E, Garcia A Denise, Fan Guoping, Imura Tetsuya, Sofroniew Michael V, Fanselow Michael S Juvenile neurogenesis makes essential contributions to adult brain structure and plays a sex-dependent role in fear memories Frontiers in behavioral neuroscience, 2012; 6(21): 3.
- Biswas Anuradha, Liu Ying, Liu Tianfei, Fan Guoping, Tang Yi Polyethylene glycol-based protein nanocapsules for functional delivery of a differentiation transcription factor Biomaterials, 2012; 33(21): 5459-67.
- Li Ji, Jiang Ting-Xin, Hughes Michael W, Wu Ping, Yu Juehua, Widelitz Randall B, Fan Guoping, Chuong Cheng-Ming Progressive alopecia reveals decreasing stem cell activation probability during aging of mice with epidermal deletion of DNA methyltransferase 1 The Journal of investigative dermatology, 2012; 132(12): 2681-90.
- Le Thuc, Kim Kee-Pyo, Fan Guoping, Faull Kym F A sensitive mass spectrometry method for simultaneous quantification of DNA methylation and hydroxymethylation levels in biological samples Analytical biochemistry, 2011; 412(2): 203-9.
- Biswas Anuradha, Joo Kye-Il, Liu Jing, Zhao Muxun, Fan Guoping, Wang Pin, Gu Zhen, Tang Yi Endoprotease-mediated intracellular protein delivery using nanocapsules ACS nano, 2011; 5(2): 1385-94.
- Huang Kevin, Fan Guoping Epigenetic modifications in distinction: histone versus DNA methylation in ESCs Cell stem cell, 2011; 8(6): 604-5.
- Wang Anyou, Huang Kevin, Shen Yin, Xue Zhigang, Cai Chaochao, Horvath Steve, Fan Guoping Functional Modules Distinguish Human Induced Pluripotent Stem Cells from Embryonic Stem Cells Stem cells and development, 2011; 130(2): .
- Dhawan Sangeeta, Georgia Senta, Tschen Shuen-Ing, Fan Guoping, Bhushan Anil Pancreatic Î² cell identity is maintained by DNA methylation-mediated repression of Arx Developmental cell, 2011; 20(4): 419-29.
- Fan Guoping, Tran Jamie X chromosome inactivation in human and mouse pluripotent stem cells Human genetics, 2011; 130(2): 217-22.
- Huang Kevin, Fan Guoping DNA methylation in cell differentiation and reprogramming: an emerging systematic view Regenerative medicine, 2010; 5(4): 531-44.
- Feng Jian, Zhou Yu, Campbell Susan L, Le Thuc, Li En, Sweatt J David, Silva Alcino J, Fan Guoping Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons Nature neuroscience, 2010; 13(4): 423-30.
- Zhong Jin, Chan Albert, Morad Leeron, Kornblum Harley I, Fan Guoping, Carmichael S Thomas Hydrogel Matrix to Support Stem Cell Survival After Brain Transplantation in Stroke Neurorehabilitation and neural repair, 2010; 285(27): .
- Hutnick Leah K, Huang Xinhua, Loo Tao-Chuan, Ma Zhicheng, Fan Guoping Repression of retrotransposal elements in mouse embryonic stem cells is primarily mediated by a DNA methylation-independent mechanism The Journal of biological chemistry, 2010; 285(27): 21082-91.
- Liu Bin, Tahk Samuel, Yee Kathleen M, Fan Guoping, Shuai Ke The ligase PIAS1 restricts natural regulatory T cell differentiation by epigenetic repression Science (New York, N.Y.), 2010; 330(6003): 521-5.
- Tamar Dvash, Neta Lavon, Guoping Fan Variations of X Chromosome Inactivation Occur in Early Passages of Female Human Embryonic Stem Cells, PLOS ONE, 2010; 5(6): e11330.
- Dvash Tamar, Lavon Neta, Fan Guoping Variations of X chromosome inactivation occur in early passages of female human embryonic stem cells PloS one, 2010; 5(6): e11330.
- Fan Zhipeng, Yamaza Takayoshi, Lee Janice S, Yu Jinhua, Wang Songlin, Fan Guoping, Shi Songtao, Wang Cun-Yu BCOR regulates mesenchymal stem cell function by epigenetic mechanisms Nature cell biology, 2009; 11(8): 1002-9.
- Hutnick Leah K, Golshani Peyman, Namihira Masakasu, Xue Zhigang, Matynia Anna, Yang X William, Silva Alcino J, Schweizer Felix E, Fan Guoping DNA hypomethylation restricted to the murine forebrain induces cortical degeneration and impairs postnatal neuronal maturation Human molecular genetics, 2009; 18(15): 2875-88.
- Dvash Tamar, Fan Guoping Epigenetic regulation of X-inactivation in human embryonic stem cells Epigenetics : official journal of the DNA Methylation Society, 2009; 4(1): 19-22.
- Mason Mike J, Fan Guoping, Plath Kathrin, Zhou Qing, Horvath Steve Signed weighted gene co-expression network analysis of transcriptional regulation in murine embryonic stem cells BMC genomics, 2009; 10(8): 327.
- Feng Jian, Fan Guoping The role of DNA methylation in the central nervous system and neuropsychiatric disorders International review of neurobiology, 2009; 89(1): 67-84.
- Fouse, S., Shen, Y., Pellegrini, M., Cole, S., Meissner, A., Van Neste, L., Jaenisch, R., Fan, G. Promoter CpG methylation contributes to ES cell gene regulation in parallel with Oct4/Nanog, PcG complex, and histone H3 K4/K27 trimethylation, Cell Stem Cell, 2008; 2(2): 160-169.
- Shen, Y., Matsuno, Y., Fouse, S., Rao, N., Root, S., Xu, R.H., Pellegrini, Riggs, A., Fan, G. X-inactivation in female human embryonic stem cells is in a non-random pattern and prone to epigenetic alterations. , Proc. Natl. Acad. Sci. USA, 2008; 105(12): 4709-4714.
- Golshani, P., Hutnick, L., Schweizer, F., Fan, G. Conditional Dnmt1 deletion in dorsal forebrain disrupts development of somatosensory barrel cortex and thalamocortical long-term potentiation Thalamus and Related System , 2007; Published online in March 2007: .
- Feng, J., Fouse, S., Fan, G. Epigenetic regulation of neural gene expression and neuronal function Pediatric Research, 2007; 61 (5 Pt 2): 58R-63R.
- Shen Y, Chow J, Wang Z, FanG Abnormal CpG island methylation occurs during in vitro differentiation of human embryonic stem cells. Human Molecular Genetics, 2006; 15(17): 2623-2635.
- He F, Ge W, Zhu W, Becker-Catania S, Martinowich K, Wu H, Coskun V, Fan G, deVellis J, Sun Y A positive autoregulation loop of JAK-STAT signaling is part of the clock mechanism regulating astrogliogenesis, Nature Neuroscience, 2005; 8: 616-625.
- Fan G, Martinowich K, Chin MH, He F, Fouse SD, Hutnick L, Hattori D, Ge W, Shen Y, Wu H, ten Hoeve J, Shuai K, Sun YE DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling Development (Cambridge, England) , 2005; 132(15): 3345-56.
- Feng J, Chang H, Li E, Fan G Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous system J Neurosci Res, 2005; 79: 734-746 (Cover art).
- Fan G, Hutnick L Methyl-CpG binding proteins in the nervous system Cell research. , 2005; 15(4): 255-61.
- Lyckman AW, Fan G, Rios M, Jaenisch R, Sur M Normal eye-specific patterning of retinal inputs to murine subcortical visual nuclei in the absence of brain-derived neurotrophic factor Visual neuroscience. , 2005; 22(1): 27-36.
- Chi MM, Fan G, Fox EA Increased short-term food satiation and sensitivity to cholecystokinin in neurotrophin-4 knock-in mice American journal of physiology. Regulatory, integrative and comparative physiology. , 2004; 287(5): R1044-53.
- Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G, Sun YE DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation Science. , 2003; 302(5646): 890-3.
- Ge W, Martinowich K, Wu X, He F, Miyamoto A, Fan G, Weinmaster G, Sun YE Notch signaling promotes astrogliogenesis via direct CSL-mediated glial gene activation Journal of neuroscience research. , 2002; 69(6): 848-60.
- Fan G, Beard C, Chen RZ, Csankovszki G, Sun Y, Siniaia M, Biniszkiewicz D, Bates B, Lee PP, Kuhn R, Trumpp A, Poon C, Wilson CB, Jaenisch R DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals The Journal of neuroscience : the official journal of the Society for Neuroscience. , 2001; 21(3): 788-97.
- Sun Y, Nadal-Vicens M, Misono S, Lin MZ, Zubiaga A, Hua X, Fan G, Greenberg ME Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms Cell. , 2001; 104(3): 365-76.
- Fan G, Copray S, Wong E, Yan Q, Jones K, Walro J, Jaenisch R, Kucera J Formation of the cranial proprioceptive system requires multiple neurotrophins, Developmental Dynamics, 2000; 218: 359-370.
- Endres M, Fan G (equal contribution), Hirt L, Fujji M, Liu X, Jaenisch R, Moskowitz MA Ischemic brain damage after selectively modifying BDNF or NT-4 expression in vivo, J. Cereb.Blood Flow. Metab, 2000; 20: 139-144.
- Fan G, Egles C, Sun Y, Minichiello L, Renger JJ, Klein R, Liu G, Jaenisch R Knocking the NT4 gene into the BDNF locus rescues BDNF deficient mice and reveals distinct NT4 and BDNF activities Nature neuroscience. , 2000; 3(4): 350-7.
- Fan G, Xiao L, Cheng L, Wang X, Sun B, Hu G Targeted disruption of NDST-1 gene leads to pulmonary hypoplasia and neonatal respiratory distress in mice FEBS letters. , 2000; 467(1): 7-11.
- Fan G, Jaenisch R, Kucera J A role for p75 receptor in NT3 functioning during the development of limb proprioception, Neuroscience, 1999; 90: 259-268.
- Bates B, Rios M, Trumpp A, Chen C, Fan G, Bishop JM, Jaenisch R Neurotrophin-3 is required for proper cerebellar development Nature neuroscience. , 1999; 2(2): 115-7.