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
Boulder, CO
postdoctoral - Biochemistry
1993
Yale University
New Haven, CT
Ph.D. - Biophysics/Biochemistry
1990
University des Saarlands
Germany
BS/MS - Chemistry
1986
In vivo structure profiling reveals human cytosolic and mitochondrial tRNA structurome and interactome in response to stress.
In vivo structure profiling reveals human cytosolic and mitochondrial tRNA structurome and interactome in response to stress. Nat Commun. 2025 May 30; 16(1):5041.
PMID: 40447571
Mammalian Queuosine tRNA Modification Impacts Translation to Enhance Cell Proliferation and MHC-II Expression.
Mammalian Queuosine tRNA Modification Impacts Translation to Enhance Cell Proliferation and MHC-II Expression. J Mol Biol. 2025 Aug 15; 437(16):169188.
PMID: 40339980
Loss of DRD5P2 in hypoxia attenuates Rock2 degradation to promote EMT and gastric cancer metastasis.
Loss of DRD5P2 in hypoxia attenuates Rock2 degradation to promote EMT and gastric cancer metastasis. Biochim Biophys Acta Mol Basis Dis. 2025 Aug; 1871(6):167858.
PMID: 40280198
Identification of EGR1 as a Key Diagnostic Biomarker in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Through Machine Learning and Immune Analysis.
Identification of EGR1 as a Key Diagnostic Biomarker in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Through Machine Learning and Immune Analysis. J Inflamm Res. 2025; 18:1639-1656.
PMID: 39925925
Cu-Catalyzed Electrochemical Activation of Nitromethane to Access Aldoxime-Substituted Nitrile Oxide for Huisgen Reaction.
Cu-Catalyzed Electrochemical Activation of Nitromethane to Access Aldoxime-Substituted Nitrile Oxide for Huisgen Reaction. Org Lett. 2024 Dec 20; 26(50):10976-10981.
PMID: 39656448
snoRNA-facilitated protein secretion revealed by transcriptome-wide snoRNA target identification.
snoRNA-facilitated protein secretion revealed by transcriptome-wide snoRNA target identification. Cell. 2025 Jan 23; 188(2):465-483.e22.
PMID: 39579764
Bioinformatics of simultaneous, quantitative measurements of full-length tRNA and tRNA fragments by MSR sequencing.
Bioinformatics of simultaneous, quantitative measurements of full-length tRNA and tRNA fragments by MSR sequencing. Methods Enzymol. 2025; 711:312-323.
PMID: 39952712
Targeting CBP revers chemoresistance to 5-FU of CDX2/REG4 double-positive gastric cancer.
Targeting CBP revers chemoresistance to 5-FU of CDX2/REG4 double-positive gastric cancer. Clin Transl Med. 2024 Nov; 14(11):e70069.
PMID: 39456121
KBr-Mediated Electrochemical Dihydroxylation of Alkenes Using H2O as the Hydroxyl Source.
KBr-Mediated Electrochemical Dihydroxylation of Alkenes Using H2O as the Hydroxyl Source. Org Lett. 2024 Oct 18; 26(41):8884-8889.
PMID: 39364937
Microbiome-induced reprogramming in post-transcriptional landscape using nanopore direct RNA sequencing.
Microbiome-induced reprogramming in post-transcriptional landscape using nanopore direct RNA sequencing. Cell Rep. 2024 10 22; 43(10):114798.
PMID: 39365698
American Association for the Advancement of Science (AAAS) Fellow
2015
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
1994
Damon Runyon-Walter Winchell Cancer Research Fund
1991 - 1993