I am a LSRF Postdoctoral Research Fellow at Stanford University, jointly advised by Prof. Alice Ting and Prof. Liqun Luo. My current research is focused on the development of molecular tools and sequencing technologies for connectome and transcriptome studies in neuronal systems.
Honors & Awards
Stanford Neurosciences Institute Interdisciplinary Scholar Awards, Stanford University (2017)
2018 RNA Society/Scaringe Graduate Student Award, RNA Society (2017)
Elizabeth R. Norton Prize for Excellence in Research in Chemistry, The University of Chicago (2017)
Graduate Council Travel Fund, The University of Chicago (2017)
GLCACS Outstanding Student Research Award, Chinese American Chemical Society (2016)
William Rainey Harper Dissertation Fellowship, The University of Chicago (2016)
Student Leadership Recognition and Access Program Award, The University of Chicago (2016)
Joan Shiu Chemistry Department Student Service Award, The University of Chicago (2016)
Collège de France Science Research Travel Grants for Doctoral Research in Paris, The University of Chicago (2016)
The Albert J. Cross Prize for Excellence in Research, Teaching, and Department Citizenship, The University of Chicago (2015)
HHMI International Student Fellowship, Howard Hughes Medical Institute (2014)
Silver Prize of 8th "Challenge Cup" National College Students Business Plan Competition, Ministry of Education / China Association for Science and Technology (2012)
Best graduation thesis and defense of Peking University, Peking University (2012)
First Prize of 1st “Star of Chemistry” Undergraduate and Graduate Selection of College of Chemistry, Peking University (2012)
Grand Prize and Technology Transfer Award of 13th Peking University Business Plan Competition, Peking University (2011)
Grand Prize of 12th "Challenge Cup" National Science and Technology Academic Competition, Ministry of Education / China Association for Science and Technology (2011)
Student Innovation Award of Peking University in 2010-2011 Academic Year, Peking University (2011)
Dow Sustainability Innovation Student Challenge Award, Dow Chemistry Company (2011)
First Runner Up and Best Environment Project of iGEM 2010, iGEM / MIT (2010)
Fangzheng Fellowship, Peking University (2008)
Boards, Advisory Committees, Professional Organizations
Member, RNA Society (2016 - Present)
Doctor of Philosophy, University of Chicago (2017)
Master of Science, University of Chicago, Chemistry (2013)
Bachelor of Science, Peking University, Chemistry (2012)
RNA-protein interaction mapping via MS2- or Cas13-based APEX targeting.
Proceedings of the National Academy of Sciences of the United States of America
RNA-protein interactions underlie a wide range of cellular processes. Improved methods are needed to systematically map RNA-protein interactions in living cells in an unbiased manner. We used two approaches to target the engineered peroxidase APEX2 to specific cellular RNAs for RNA-centered proximity biotinylation of protein interaction partners. Both an MS2-MCP system and an engineered CRISPR-Cas13 system were used to deliver APEX2 to the human telomerase RNA hTR with high specificity. One-minute proximity biotinylation captured candidate binding partners for hTR, including more than a dozen proteins not previously linked to hTR. We validated the interaction between hTR and the N 6-methyladenosine (m6A) demethylase ALKBH5 and showed that ALKBH5 is able to erase the m6A modification on endogenous hTR. ALKBH5 also modulates telomerase complex assembly and activity. MS2- and Cas13-targeted APEX2 may facilitate the discovery of novel RNA-protein interactions in living cells.
View details for DOI 10.1073/pnas.2006617117
View details for PubMedID 32839320
m(6)A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition
2017; 542 (7642): 475-?
The maternal-to-zygotic transition (MZT) is one of the most profound and tightly orchestrated processes during the early life of embryos, yet factors that shape the temporal pattern of vertebrate MZT are largely unknown. Here we show that over one-third of zebrafish maternal messenger RNAs (mRNAs) can be N6-methyladenosine (m6A) modified, and the clearance of these maternal mRNAs is facilitated by an m6A-binding protein, Ythdf2. Removal of Ythdf2 in zebrafish embryos decelerates the decay of m6A-modified maternal mRNAs and impedes zygotic genome activation. These embryos fail to initiate timely MZT, undergo cell-cycle pause, and remain developmentally delayed throughout larval life. Our study reveals m6A-dependent RNA decay as a previously unidentified maternally driven mechanism that regulates maternal mRNA clearance during zebrafish MZT, highlighting the critical role of m6A mRNA methylation in transcriptome switching and animal development.
View details for DOI 10.1038/nature21355
View details for Web of Science ID 000395094100036
View details for PubMedID 28192787
View details for PubMedCentralID PMC5323276
- Post-transcriptional gene regulation by mRNA modifications NATURE REVIEWS MOLECULAR CELL BIOLOGY 2017; 18 (1): 31-42
N-6-methyladenosine Modulates Messenger RNA Translation Efficiency
2015; 161 (6): 1388-1399
N(6)-methyladenosine (m(6)A) is the most abundant internal modification in mammalian mRNA. This modification is reversible and non-stoichiometric and adds another layer to the dynamic control of mRNA metabolism. The stability of m(6)A-modified mRNA is regulated by an m(6)A reader protein, human YTHDF2, which recognizes m(6)A and reduces the stability of target transcripts. Looking at additional functional roles for the modification, we find that another m(6)A reader protein, human YTHDF1, actively promotes protein synthesis by interacting with translation machinery. In a unified mechanism of m(6)A-based regulation in the cytoplasm, YTHDF2-mediated degradation controls the lifetime of target transcripts, whereas YTHDF1-mediated translation promotion increases translation efficiency, ensuring effective protein production from dynamic transcripts that are marked by m(6)A. Therefore, the m(6)A modification in mRNA endows gene expression with fast responses and controllable protein production through these mechanisms.
View details for DOI 10.1016/j.cell.2015.05.014
View details for Web of Science ID 000355935000017
View details for PubMedID 26046440
DNA 5-Methylcytosine-Specific Amplification and Sequencing.
Journal of the American Chemical Society
DNA 5-methylcytosine (5mC)-specific mapping has been hampered by severe DNA degradation and the presence of 5-hydroxymethylcytosine (5hmC) using the conventional bisulfite sequencing approach. Here, we present a 5mC-specific whole-genome amplification method (5mC-WGA), with which we achieved 5mC retention during DNA amplification from limited input down to 10 pg scale with limited interference from 5hmC signals, providing DNA 5mC methylome with high reproducibility and accuracy.
View details for DOI 10.1021/jacs.9b12707
View details for PubMedID 32077696
- "Gamete On" for m6A: YTHDF2 Exerts Essential Functions in Female Fertility. Molecular cell 2017; 67 (6): 903-905
m(6)A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program
2017; 31 (4): 591-?
The dynamic and reversible N6-methyladenosine (m6A) RNA modification installed and erased by N6-methyltransferases and demethylases regulates gene expression and cell fate. We show that the m6A demethylase ALKBH5 is highly expressed in glioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppresses the proliferation of patient-derived GSCs. Integrated transcriptome and m6A-seq analyses revealed altered expression of certain ALKBH5 target genes, including the transcription factor FOXM1. ALKBH5 demethylates FOXM1 nascent transcripts, leading to enhanced FOXM1 expression. Furthermore, a long non-coding RNA antisense to FOXM1 (FOXM1-AS) promotes the interaction of ALKBH5 with FOXM1 nascent transcripts. Depleting ALKBH5 and FOXM1-AS disrupted GSC tumorigenesis through the FOXM1 axis. Our work uncovers a critical function for ALKBH5 and provides insight into critical roles of m6A methylation in glioblastoma.
View details for DOI 10.1016/j.ccell.2017.02.013
View details for PubMedID 28344040
- YTHDF3 facilitates translation and decay of N-6-methyladenosine-modified RNA CELL RESEARCH 2017; 27 (3): 315-328
- Evolution of transcript modification by N-6-methyladenosine in primates GENOME RESEARCH 2017; 27 (3): 385-392
Dynamics of Human and Viral RNA Methylation during Zika Virus Infection
CELL HOST & MICROBE
2016; 20 (5): 666-673
Infection with the flavivirus Zika (ZIKV) causes neurological, immunological, and developmental defects through incompletely understood mechanisms. We report that ZIKV infection affects viral and human RNAs by altering the topology and function of N6-adenosine methylation (m6A), a modification affecting RNA structure and function. m6A nucleosides are abundant in ZIKV RNA, with twelve m6A peaks identified across full-length ZIKV RNA. m6A in ZIKV RNA is controlled by host methyltransferases METTL3 and METTL14 and demethylases ALKBH5 and FTO, and knockdown of methyltransferases increases, while silencing demethylases decreases, ZIKV production. YTHDF family proteins, which regulate the stability of m6A-modified RNA, bind to ZIKV RNA, and their silencing increases ZIKV replication. Profiling of the m6A methylome of host mRNAs reveals that ZIKV infection alters m6A location in mRNAs, methylation motifs, and target genes modified by methyltransferases. Our results identify a mechanism by which ZIKV interacts with and alters host cell functions.
View details for DOI 10.1016/j.chom.2016.10.002
View details for Web of Science ID 000389472000015
View details for PubMedID 27773536
View details for PubMedCentralID PMC5155635
Quantifying mammalian genomic DNA hydroxymethylcytosine content using solid-state nanopores
5-hydroxymethylcytosine (5 hmC), the oxidized form of 5-methylcytosine (5 mC), is a base modification with emerging importance in biology and disease. However, like most epigenetic elements, it is transparent to many conventional genetic techniques and is thus challenging to probe. Here, we report a rapid solid-state nanopore assay that is capable of resolving 5 hmC with high specificity and sensitivity and demonstrate its utility in assessing global modification abundance in genomic DNA.
View details for DOI 10.1038/srep29565
View details for Web of Science ID 000379160200001
View details for PubMedID 27383905
View details for PubMedCentralID PMC4935868
N-6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression
The internal N(6)-methyladenosine (m(6)A) methylation of eukaryotic nuclear RNA controls post-transcriptional gene expression, which is regulated by methyltransferases (writers), demethylases (erasers), and m(6)A-binding proteins (readers) in cells. The YTH domain family proteins (YTHDF1-3) bind to m(6)A-modified cellular RNAs and affect RNA metabolism and processing. Here, we show that YTHDF1-3 proteins recognize m(6)A-modified HIV-1 RNA and inhibit HIV-1 infection in cell lines and primary CD4(+) T-cells. We further mapped the YTHDF1-3 binding sites in HIV-1 RNA from infected cells. We found that the overexpression of YTHDF proteins in cells inhibited HIV-1 infection mainly by decreasing HIV-1 reverse transcription, while knockdown of YTHDF1-3 in cells had the opposite effects. Moreover, silencing the m(6)A writers decreased HIV-1 Gag protein expression in virus-producing cells, while silencing the m(6)A erasers increased Gag expression. Our findings suggest an important role of m(6)A modification of HIV-1 RNA in viral infection and HIV-1 protein synthesis.
View details for DOI 10.7554/eLife.15528
View details for Web of Science ID 000380858000001
View details for PubMedID 27371828
View details for PubMedCentralID PMC4961459
Nucleic Acid Modifications in Regulation of Gene Expression
CELL CHEMICAL BIOLOGY
2016; 23 (1): 74-85
Nucleic acids carry a wide range of different chemical modifications. In contrast to previous views that these modifications are static and only play fine-tuning functions, recent research advances paint a much more dynamic picture. Nucleic acids carry diverse modifications and employ these chemical marks to exert essential or critical influences in a variety of cellular processes in eukaryotic organisms. This review covers several nucleic acid modifications that play important regulatory roles in biological systems, especially in regulation of gene expression: 5-methylcytosine (5mC) and its oxidative derivatives, and N(6)-methyladenine (6mA) in DNA; N(6)-methyladenosine (m(6)A), pseudouridine (Ψ), and 5-methylcytidine (m(5)C) in mRNA and long non-coding RNA. Modifications in other non-coding RNAs, such as tRNA, miRNA, and snRNA, are also briefly summarized. We provide brief historical perspective of the field, and highlight recent progress in identifying diverse nucleic acid modifications and exploring their functions in different organisms. Overall, we believe that work in this field will yield additional layers of both chemical and biological complexity as we continue to uncover functional consequences of known nucleic acid modifications and discover new ones.
View details for DOI 10.1016/j.chembiol.2015.11.007
View details for Web of Science ID 000381507100008
View details for PubMedID 26933737
View details for PubMedCentralID PMC4779186
- TET Family Proteins: Oxidation Activity, Interacting Molecules, and Functions in Diseases CHEMICAL REVIEWS 2015; 115 (6): 2225-2239
- Base-resolution maps of 5-formylcytosine and 5-carboxylcytosine reveal genome-wide DNA demethylation dynamics CELL RESEARCH 2015; 25 (3): 386-389
Fate by RNA methylation: m(6)A steers stem cell pluripotency
The N 6-methyladenosine (m6A) modification of mRNA has a crucial function in regulating pluripotency in murine stem cells: it facilitates resolution of naïve pluripotency towards differentiation.
View details for DOI 10.1186/s13059-015-0609-1
View details for Web of Science ID 000351822800003
View details for PubMedID 25723450
View details for PubMedCentralID PMC4336730
Pseudouridine in a new era of RNA modifications
2015; 25 (2): 153-154
Two articles recently published in Nature and Cell report the first transcriptome-wide maps of pseudouridine (Ψ) at single-base resolution through selective chemical labeling, suggesting new mechanisms and functions of Ψ in mRNA and non-coding RNA molecules.
View details for DOI 10.1038/cr.2014.143
View details for Web of Science ID 000349334100003
View details for PubMedID 25367125
View details for PubMedCentralID PMC4650566
5mC Oxidation by Tet2 Modulates Enhancer Activity and Timing of Transcriptome Reprogramming during Differentiation
2014; 56 (2): 286-297
In mammals, cytosine methylation (5mC) is widely distributed throughout the genome but is notably depleted from active promoters and enhancers. While the role of DNA methylation in promoter silencing has been well documented, the function of this epigenetic mark at enhancers remains unclear. Recent experiments have demonstrated that enhancers are enriched for 5-hydroxymethylcytosine (5hmC), an oxidization product of the Tet family of 5mC dioxygenases and an intermediate of DNA demethylation. These results support the involvement of Tet proteins in the regulation of dynamic DNA methylation at enhancers. By mapping DNA methylation and hydroxymethylation at base resolution, we find that deletion of Tet2 causes extensive loss of 5hmC at enhancers, accompanied by enhancer hypermethylation, reduction of enhancer activity, and delayed gene induction in the early steps of differentiation. Our results reveal that DNA demethylation modulates enhancer activity, and its disruption influences the timing of transcriptome reprogramming during cellular differentiation.
View details for DOI 10.1016/j.molcel.2014.08.026
View details for Web of Science ID 000344484600010
View details for PubMedID 25263596
View details for PubMedCentralID PMC4319980
The multiple antibiotic resistance regulator MarR is a copper sensor in Escherichia coli
NATURE CHEMICAL BIOLOGY
2014; 10 (1): 21-U48
The widely conserved multiple antibiotic resistance regulator (MarR) family of transcription factors modulates bacterial detoxification in response to diverse antibiotics, toxic chemicals or both. The natural inducer for Escherichia coli MarR, the prototypical transcription repressor within this family, remains unknown. Here we show that copper signaling potentiates MarR derepression in E. coli. Copper(II) oxidizes a cysteine residue (Cys80) on MarR to generate disulfide bonds between two MarR dimers, thereby inducing tetramer formation and the dissociation of MarR from its cognate promoter DNA. We further discovered that salicylate, a putative MarR inducer, and the clinically important bactericidal antibiotics norfloxacin and ampicillin all stimulate intracellular copper elevation, most likely through oxidative impairment of copper-dependent envelope proteins, including NADH dehydrogenase-2. This membrane-associated copper oxidation and liberation process derepresses MarR, causing increased bacterial antibiotic resistance. Our study reveals that this bacterial transcription regulator senses copper(II) as a natural signal to cope with stress caused by antibiotics or the environment.
View details for DOI 10.1038/NCHEMBIO.1380
View details for Web of Science ID 000328854900006
View details for PubMedID 24185215
A highly sensitive and genetically encoded fluorescent reporter for ratiometric monitoring of quinones in living cells
2013; 49 (73): 8027-8029
The transcriptional regulator QsrR is converted into a genetically encoded fluorescent probe capable of ratiometric monitoring of quinones in living cells with high sensitivity and selectivity.
View details for DOI 10.1039/c3cc44534h
View details for Web of Science ID 000323195600012
View details for PubMedID 23903292
View details for PubMedCentralID PMC4007278
Probing subcellular organic hydroperoxide formation via a genetically encoded ratiometric and reversible fluorescent indicator
2013; 5 (12): 1485-1489
A ratiometric and reversible organic hydroperoxide (OHP) sensor, rOHSer, was developed with high sensitivity and selectivity for subcellular OHP visualization. Through targeting rOHSer to the nucleus, we demonstrated that high levels of D-glucose cause elevated OHP production in this compartment. Further utilization of rOHSer probe may allow more elucidation of unique roles of OHPs in diverse biological processes.
View details for DOI 10.1039/c3ib40209f
View details for Web of Science ID 000327260600007
View details for PubMedID 24190510
- A Selective Fluorescent Probe for Carbon Monoxide Imaging in Living Cells ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2012; 51 (38): 9652-9656
A Highly Selective Fluorescent Probe for Visualization of Organic Hydroperoxides in Living Cells
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2010; 132 (48): 17065-17067
The transcriptional regulatory protein OhrR is converted into a fluorescent bioprobe capable of detecting organic hydroperoxides in living cells with high sensitivity and selectivity.
View details for DOI 10.1021/ja1071114
View details for Web of Science ID 000285080400005
View details for PubMedID 21077671