Our research focuses on (i) functional genomics and biology of tRNA including microbiomes and (ii) epitranscriptomics including microbiome-host interactions.
tRNA biology: Translational regulation relies on the dynamic properties of tRNA that constantly change to facilitate response and adaptation to new environments and to control gene expression. We developed high throughput sequencing technologies that measure tRNA abundance, charging and modifications in one single sequencing library. We are investigating the roles of tRNA in translational control and extra-translational functions in mammalian cells.
Microbiome: We also developed tRNA-seq as another approach for microbiome characterization. Standard microbiome characterizations include 16S-seq or shotgun metagenomics. Although powerful, these DNA-based methods do not directly report the microbiome activity such as dynamic gene expression which requires the studies of RNA in the microbiome. Our microbiome tRNA-seq results show extensive variations of tRNA abundance and modification patterns in microbiomes from different sources. We also show that tRNA modification dynamics in the microbiome correlates with tuning the expression of specific microbial proteins, indicating that tRNA-seq can provide new insights in microbiome biology. We are further developing this approach to explore the potentials of tRNA-seq to study microbiomes from humans and from the oceans.
Epitranscriptomics: Over 100 types of post-transcriptional RNA modifications have been identified in thousands of sites in the transcriptome. They include methylation of bases and the ribose backbone, rotation and reduction of uridine, base deamination, addition of ring structures and carbohydrate moieties, and so on. mRNA modifications are involved in cell differentiation, proliferation, and many other cellular functions and human diseases. Some mRNA modifications can also be removed by cellular enzymes, resulting in the dynamic regulation of their functions. We are investigating the function and mechanisms of mRNA modifications such as N6-methyladenosine (m6A) in the regulation of gene expression. For example, we discovered that m6A modification can alter the local mRNA structure to regulate binding of mRNA binding proteins transcriptome-wide (m6A switch), resulting in changes in mRNA abundance and alternative splicing.
Microbiome-host interactions through epitranscriptomics: We are working on elucidating the function of mammalian host mRNA and tRNA modifications in response to the gut microbiome. We found that microbiome reprograms the host m6A modifications transcriptome-wide in a tissue-dependent manner, suggesting that this dynamic epitranscriptomic mark is used in yet unknown ways in microbiome response. We also found that a microbiome dependent, host tRNA modification alters the cellular small RNA pool, suggesting yet another pathway of microbiome response through RNA modifications.
University of Colorado at Boulder
postdoctoral - Biochemistry
New Haven, CT
Ph.D. - Biophysics/Biochemistry
University des Saarlands
BS/MS - Chemistry
A high-throughput screening method for evolving a demethylase enzyme with improved and new functionalities.
Wang Y, Katanski CD, Watkins C, Pan JN, Dai Q, Jiang Z, Pan T. A high-throughput screening method for evolving a demethylase enzyme with improved and new functionalities. Nucleic Acids Res. 2020 Dec 18.
Cross-editing by a tRNA synthetase allows vertebrates to abundantly express mischargeable tRNA without causing mistranslation.
Chen M, Kuhle B, Diedrich J, Liu Z, Moresco JJ, Yates Iii JR, Pan T, Yang XL. Cross-editing by a tRNA synthetase allows vertebrates to abundantly express mischargeable tRNA without causing mistranslation. Nucleic Acids Res. 2020 07 09; 48(12):6445-6457.
5-Methylcytosine RNA Modifications Promote Retrovirus Replication in an ALYREF Reader Protein-Dependent Manner.
Eckwahl M, Xu R, Michalkiewicz J, Zhang W, Patel P, Cai Z, Pan T. 5-Methylcytosine RNA Modifications Promote Retrovirus Replication in an ALYREF Reader Protein-Dependent Manner. J Virol. 2020 06 16; 94(13).
Nosocomial outbreak of COVID-19 pneumonia in Wuhan, China.
Wang X, Zhou Q, He Y, Liu L, Ma X, Wei X, Jiang N, Liang L, Zheng Y, Ma L, Xu Y, Yang D, Zhang J, Yang B, Jiang N, Deng T, Zhai B, Gao Y, Liu W, Bai X, Pan T, Wang G, Chang Y, Zhang Z, Shi H, Ma WL, Gao Z. Nosocomial outbreak of COVID-19 pneumonia in Wuhan, China. Eur Respir J. 2020 06; 55(6).
Detection and quantification of glycosylated queuosine modified tRNAs by acid denaturing and APB gels.
Zhang W, Xu R, Matuszek Z, Cai Z, Pan T. Detection and quantification of glycosylated queuosine modified tRNAs by acid denaturing and APB gels. RNA. 2020 09; 26(9):1291-1298.
Cathepsin L promotes angiogenesis by regulating the CDP/Cux/VEGF-D pathway in human gastric cancer.
Pan T, Jin Z, Yu Z, Wu X, Chang X, Fan Z, Li F, Wang X, Li Z, Zhou Q, Li J, Liu B, Su L. Cathepsin L promotes angiogenesis by regulating the CDP/Cux/VEGF-D pathway in human gastric cancer. Gastric Cancer. 2020 11; 23(6):974-987.
tRNA Queuosine Modification Enzyme Modulates the Growth and Microbiome Recruitment to Breast Tumors.
Zhang J, Lu R, Zhang Y, Matuszek Z, Zhang W, Xia Y, Pan T, Sun J. tRNA Queuosine Modification Enzyme Modulates the Growth and Microbiome Recruitment to Breast Tumors. Cancers (Basel). 2020 Mar 09; 12(3).
HIV protease cleaves the antiviral m6A reader protein YTHDF3 in the viral particle.
Jurczyszak D, Zhang W, Terry SN, Kehrer T, Bermúdez González MC, McGregor E, Mulder LCF, Eckwahl MJ, Pan T, Simon V. HIV protease cleaves the antiviral m6A reader protein YTHDF3 in the viral particle. PLoS Pathog. 2020 02; 16(2):e1008305.
A dual function PUS enzyme.
Zhang W, Pan T. A dual function PUS enzyme. Nat Chem Biol. 2020 02; 16(2):107-108.
Self-cleaning isotype g-C3N4 heterojunction for efficient photocatalytic reduction of hexavalent uranium under visible light.
Le Z, Xiong C, Gong J, Wu X, Pan T, Chen Z, Xie Z. Self-cleaning isotype g-C3N4 heterojunction for efficient photocatalytic reduction of hexavalent uranium under visible light. Environ Pollut. 2020 May; 260:114070.
American Association for the Advancement of Science (AAAS) Fellow
NIH Director’s Pioneer award
2011 - 2016
NIH EUREKA award
2009 - 2013
American Cancer Society, Junior Faculty Research Award
1995 - 1997
Cancer Research Foundation, Raymond F. Zelko Young Investigator
Damon Runyon-Walter Winchell Cancer Research Fund
1991 - 1993