I am an HHMI Predoctoral Research Fellow at the University of Chicago, currently pursuing my Ph.D. degree under the mentorship of Prof. Chuan He in the Chemistry Department. My graduate work studies DNA and RNA epigenetics, specifically the chemical modifications on nucleic acid bases and the regulatory roles of these marks. My current research focuses on reversible RNA methylation (m6A), a re-discovered modification that has been recently revealed to carry crucial regulatory functions in mRNA. I am investigating the impacts of m6A in diverse biological systems, such as animal early development and infectious diseases.
GCIS E307, 929 E 57th St
Chicago, IL 60637 US
Ph.D. in Chemistry • August 2017
M.S. in Chemistry • October 2013
B.S. in Chemistry • June 2012
HHMI Predoctoral Student Research Fellow and Graduate Student Researcher• September 2012 - Present
Boxuan joined Prof. Chuan He’s group to continue his work at the interface of chemistry and biology. During his first year, he completed and published the work of constructing a quinone biosensor with labmate while satisfying all the coursework requirements and TA responsibilities. Starting from his second year passing candidacy, Boxuan turned his focus to the study of DNA and RNA epigenetics, specifically the investigation of chemical modifications on nucleic acid bases and the regulatory roles of these marks. He developed the first high-throughput single-base resolution sequencing methods for detecting 5fC and 5caC modifications in DNA with coworkers, and studied reversible RNA methylation (m6A) with crucial regulatory functions in mRNA. He primarily focused on the investigation of a class of RNA binding proteins that specifically recognized m6A, termed ‘m6A readers’, and jointly characterized and demonstrated the function of the first discovered translation-promoting m6A reader, YTHDF1. He then dived into the investigation of biological functions of m6A, including discovering the impact of m6A during early embryogenesis of zebrafish, revealing the distribution and effects of m6A in many virus species and viral infection. For his final year of graduate study, Boxuan plans to continue studying the functions of m6A in different biological systems and explore the crosstalk between m6A regulatory mechanism with other known pathways, in hopes of providing a clearer picture of the wide-spread biological impacts of m6A and contributing to the proceeding of the research field of RNA.
Undergraduate Researcher • January 2009 - August 2012
Boxuan started as an independent undergraduate researcher during his first year in college under the mentorship of Prof. Peng Chen, focusing on the development of biosensors for small molecules in living cells via protein engineering. His first project was to construct a genetically encoded biosensor for organic hydroperoxide (OHP) in living cells, an elusive form of reactive oxygen species that may cause severe cellular damages. Utilizing a naturally occurring OHP-sensory bacterial protein OhrR, Boxuan inserted a sensitive fluorescent protein at the predicted conformational switching region of OhrR and developed an OHP selective biosensor that changes fluorescence signal upon detecting the presence of OHP. He continues to work on the biological applications of OHP sensors and later demonstrated their functions at subcellular precision, providing the field with a useful tool for OHP detection.
Subgroup Leader • January 2010 - January 2012
Boxuan joined the research team of International Genetically Engineered Machine competition (iGEM) at Peking University and was actively engaged in the study of synthetic biology with a team of undergraduate researchers under the supervision of Prof. Qi Ouyang at the Center for Quantitative Biology. Working towards the goal of developing a biological solution for heavy metal purification, he led the subgroup of heavy metal bacterial absorbent and together with team members won second place at 2010’s iGEM Jamboree at MIT.
•Boxuan Simen Zhao, Ian A. Roundtree, and Chuan He. Post-transcriptional gene regulation by the messenger RNA modification marks, Nat. Rev. Mol. Cell Biol., advanced publication, doi:10.1038/nrm.2016.132.
•Gianluigi Lichinchi*, Boxuan Simen Zhao*, Yinga Wu, Zhike Lu, Yue Qin, Chuan He, and Tariq M. Rana. Dynamics of Human and Viral RNA Methylation during ZIKA Virus Infection, Cell Host Microbe, advanced publication, http://dx.doi.org/10.1016/j.chom.2016.10.002.
•Nagaraja Tirumuru*, Boxuan Simen Zhao*, Zhike Lu, Chuan He, and Li Wu, YTHDF Proteins Bind to N6-methyladenosines of HIV-1 RNA and Regulate Viral Infection, Elife., 2016, 5:e15528.
•Osama Zahid, Boxuan Simen Zhao, Chuan He, and Adam Hall, Quantifying mammalian genomic DNA hydroxymethylcytosine content using solid-state nanopores, Sci. Rep., 2016, 6:29565.
•Kai Chen, Boxuan Simen Zhao, and Chuan He, Nucleic Acid Modifications in Regulation of Gene Expression, Cell Chem. Biol., 2016, 23(1), pp. 74-85.
•Xiao Wang*, Boxuan Simen Zhao*, Ian A. Roundtree, Zhike Lu, Dali Han, Honghui Ma, Xiaocheng Weng, Kai Chen, Hailing Shi, and Chuan He. N6-methyladenosine Modulates Messenger RNA Translation Efficiency, Cell, 2015, 161(6), pp. 1388–1399.
•Boxuan Simen Zhao and Chuan He, Fate by RNA Methylation: m6A Steers Stem Cell Pluripotency, Genome Biol., 2015, 16, pp. 43.
•Xingyu Lu, Boxuan Simen Zhao, and Chuan He, TET Family Proteins: Oxidation Activity, Interacting Molecules, and Functions in Diseases, Chem. Rev., 2015, 115 (6), pp. 2225–2239.
•Xingyu Lu*, Dali Han*, Boxuan Simen Zhao*, Chun-Xiao Song, Li-Sheng Zhang, Louis C Doré, and Chuan He, Base-Resolution Maps of 5-Formylcytosine and 5-Carboxylcytosine Reveal Genome-Wide DNA Demethylation Dynamics, Cell Res., 2015, 25, pp. 386–389.
•Boxuan Simen Zhao, and Chuan He, Pseudouridine in a New Era of RNA Modifications, Cell Res., 2015, 25, pp. 153–154.
•Gary C. Hon, Chun-Xiao Song, Tingting Du, Fulai Jin, Siddarth Selvaraj, Ah Young Lee, Chia-an Yen, Zhen Ye, Shi-Qing Mao, Bang-An Wang, Samantha Kuan, Lee E. Edsall, Boxuan Simen Zhao, Guoliang Xu, Chuan He, and Bing Ren, 5mc Oxidation by Tet2 Modulates Enhancer Activity and Timing of Transcriptome Reprogramming During Differentiation. Mol. Cell, 2014, 56(2), pp. 286-297.
•Ziyang Hao, Hubin Lou, Rongfeng Zhu, Jiuhe Zhu, Dianmu Zhang, Boxuan Simen Zhao, Shizhe Zeng, Xing Chen, Jefferson Chan, Chuan He, and Peng R. Chen, The Multiple Antibiotic Resistance Regulator MarR is a Copper Sensor in Escherichia coli, Nat. Chem. Biol., 2014, 10, pp. 21-28.
•Boxuan Simen Zhao, Gong Zhang, Shizhe Zeng, Chuan He, and Peng R. Chen, Probing Subcellular Organic Hydroperoxide Formation via a Genetically Encoded Ratiometric and Reversible Fluorescent Indicator, Integr. Biol., 2013, 5(12), pp. 1485-1489.
•Quanjiang Ji*, Boxuan Simen Zhao*, and Chuan He, A Highly Sensitive Fluorescent Reporter for Ratiometric Monitoring of Cellular Quinones, Chem. Comm. 2013, 49(73), pp. 8027-8029.
•Jing Wang, Jason Karpus, Boxuan Simen Zhao, Zheng Luo, Peng R. Chen, and Chuan He, A Selective Fluorescent Probe for Carbon Monoxide Imaging in Living Cells, Angew. Chem. Int. Ed., 2012, 51 (38), pp. 9652–9656.
•Boxuan Simen Zhao, Yujie Liang, Yanqun Song, Chunhong Zheng, Ziyang Hao, and Peng R. Chen, A Highly Selective Fluorescent Probe for Visualization of Organic Hydroperoxides in Living Cells, J. Am. Chem. Soc., 2010, 132(48), pp. 17065–17067.
(*co-authors contributed equally)
The maternal-to-zygotic transition (MZT) is one of the most profound and orchestrated processes during the early life of embryos. We have found that m6A-dependent RNA decay as a previously unidentified maternally driven mechanism regulating maternal mRNA clearance during zebrafish MZT, highlighting the critical role of m6A mRNA methylation in animal development. Without zebrafish Ythdf2, m6A-modified maternal RNA are overrepresented in the transcriptome during MZT, causing delayed zygotic genome activation and a significant developmental delay.RNA epigenetics, m6A, Zebrafish development
The infection of Zika virus (ZIKV) causes severe neurological, immunological, and developmental defects in human patients. We discovered that ZIKV genome contains high levels of m6A, and its infection affects host m6A patterns across transcriptome. m6A in ZIKV RNA is controlled by host methyltransferases and demethylases, which has an overall repressive function on the replication of ZIKV.RNA epigenetics, m6A, Zika virus
HIV infection is a global health challenge and is hard to eliminate due to limited understanding of the replication mechanism. We discovered that in the host nucleus, the m6A methyltransferases add m6A to HIV-1 genomic RNA (gRNA) or mRNA, and the m6A demethylases remove the m6A modifications of HIV-1 RNA. The m6A modification of HIV-1 RNA can promote viral protein translation in cells. In contrast, cytoplasmic m6A readers (YTHDF1–3) bind to m6A-modified HIV-1 gRNA, which can result in inhibition of HIV-1 reverse transcription (RT), viral mRNA expression, and thereby HIV-1 infection in cells.RNA epigenetics, m6A, HIV
N6-methyladenosine (m6A) exerts its biological functions through the interaction with m6A-specific binding proteins (m6A readers). We characterized the first translation-promoting m6A reader, YTHDF1. YTHDF1 plays two key roles in the translation of m6A-modified mRNAs: it shuttles more mRNAs to translation machinery and accelerates the translation initiation rate of methylated mRNAs. The function of YTHDF1 in promoting mRNA translation efficiency, when combined with functions of other m6A readers, allows for more precise and effective control of protein production during various biological transformationsRNA epigenetics, m6A, RNA binding protein
5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) are oxidative derivatives of 5-methylcytosine (5mC) and selectively excised by mammalian thymine DNA glycosylase to restored to normal cytosine through base excision repair, enabling the process of active DNA demethylation. We developed the first method for single-base resolution detection of 5fC and 5caC in mouse ESCs (DIP-CAB-seq). We revealed a genome-wide gradient of 5mC oxidation activity at regulatory elements, which positively correlates with enhancer activity and negatively correlates with 5mC abundance. 5fC and 5caC both mark more active regulatory elements yet have disctint distribution patterns, suggesting their unique roles in epigenetic regulation at different functional elements.DNA epigenetics, 5fC, 5caC
Metal binding peptide (MBP) for mercury (II) was designed and constructed as a single polypeptide consisting of two dimerization helixes and metal binding loops of MerR (binds mercury ions), to form an antiparallel coiled coil MBP mimicking the dimerized metal binding domains of the wild-type protern. Similar strategy was used to construct another MBP for lead (II) using PbrR.Protein engineering, Heavy metal detoxification
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.Protein engineering, Quinone
Construction of a genetically encoded biosensor for organic hydroperoxide (OHP) in living cells: OHP is an elusive form of reactive oxygen species that may cause severe cellular damages. Utilizing a naturally occurring OHP-sensory bacterial protein OhrR, a sensitive fluorescent protein was inserted at the predicted conformational switching region of OhrR, resulting in an OHP selective biosensor that changes fluorescence signal upon detecting the presence of OHP.Protein engineering, OHP