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
Clinical impact of Fn-induced high expression of KIR2DL1 in CD8 T lymphocytes in oesophageal squamous cell carcinoma.
Wang X, Liu Y, Lu Y, Chen S, Xing Y, Yang H, Wang X, Zhang Y, Pan T, Li J, Wang M, Zhang N, Liang M, Zhou F. Clinical impact of Fn-induced high expression of KIR2DL1 in CD8 T lymphocytes in oesophageal squamous cell carcinoma. Ann Med. 2022 Dec; 54(1):51-62.
Analysis of queuosine and 2-thio tRNA modifications by high throughput sequencing.
Katanski CD, Watkins CP, Zhang W, Reyer M, Miller S, Pan T. Analysis of queuosine and 2-thio tRNA modifications by high throughput sequencing. Nucleic Acids Res. 2022 09 23; 50(17):e99.
Age-related endoplasmic reticulum stress represses testosterone synthesis via attenuation of the circadian clock in Leydig cells.
Gao L, Gao D, Zhang J, Li C, Wu M, Xiao Y, Yang L, Ma T, Wang X, Zhang M, Yang D, Pan T, Zhang H, Wang A, Jin Y, Chen H. Age-related endoplasmic reticulum stress represses testosterone synthesis via attenuation of the circadian clock in Leydig cells. Theriogenology. 2022 Sep 01; 189:137-149.
Pan-cancer assessment of mutational landscape in intrinsically disordered hotspots reveals potential driver genes.
Zou H, Pan T, Gao Y, Chen R, Li S, Guo J, Tian Z, Xu G, Xu J, Ma Y, Li Y. Pan-cancer assessment of mutational landscape in intrinsically disordered hotspots reveals potential driver genes. Nucleic Acids Res. 2022 05 20; 50(9):e49.
A multiplex platform for small RNA sequencing elucidates multifaceted tRNA stress response and translational regulation.
Watkins CP, Zhang W, Wylder AC, Katanski CD, Pan T. A multiplex platform for small RNA sequencing elucidates multifaceted tRNA stress response and translational regulation. Nat Commun. 2022 05 05; 13(1):2491.
The Role of the P1 Latency in Auditory and Speech Performance Evaluation in Cochlear Implanted Children.
Xiong S, Jiang L, Wang Y, Pan T, Ma F. The Role of the P1 Latency in Auditory and Speech Performance Evaluation in Cochlear Implanted Children. Neural Plast. 2022; 2022:6894794.
Profiling Selective Packaging of Host RNA and Viral RNA Modification in SARS-CoV-2 Viral Preparations.
Peña N, Zhang W, Watkins C, Halucha M, Alshammary H, Hernandez MM, Liu WC, Albrecht RA, Garcia-Sastre A, Simon V, Katanski C, Pan T. Profiling Selective Packaging of Host RNA and Viral RNA Modification in SARS-CoV-2 Viral Preparations. Front Cell Dev Biol. 2022; 10:768356.
tRNA modification dynamics from individual organisms to metaepitranscriptomics of microbiomes.
Zhang W, Foo M, Eren AM, Pan T. tRNA modification dynamics from individual organisms to metaepitranscriptomics of microbiomes. Mol Cell. 2022 03 03; 82(5):891-906.
Interferon inducible pseudouridine modification in human mRNA by quantitative nanopore profiling.
Huang S, Zhang W, Katanski CD, Dersh D, Dai Q, Lolans K, Yewdell J, Eren AM, Pan T. Interferon inducible pseudouridine modification in human mRNA by quantitative nanopore profiling. Genome Biol. 2021 12 06; 22(1):330.
ImmReg: the regulon atlas of immune-related pathways across cancer types.
Jiang T, Zhou W, Chang Z, Zou H, Bai J, Sun Q, Pan T, Xu J, Li Y, Li X. ImmReg: the regulon atlas of immune-related pathways across cancer types. Nucleic Acids Res. 2021 12 02; 49(21):12106-12118.
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