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
tRNA as an assembly chaperone for a macromolecular transcription-processing complex.
tRNA as an assembly chaperone for a macromolecular transcription-processing complex. Nat Struct Mol Biol. 2025 Nov; 32(11):2349-2358.
PMID: 40908366
Aging population of tracheal, bronchus, and lung cancer: global, regional, and national burden-insights from the Global Burden of Disease Study 2021.
Aging population of tracheal, bronchus, and lung cancer: global, regional, and national burden-insights from the Global Burden of Disease Study 2021. J Thorac Dis. 2025 Aug 31; 17(8):5547-5560.
PMID: 40950915
Size-dependent effects of the intestinal microbiota in juvenile Chinese alligators: implications for species protection.
Size-dependent effects of the intestinal microbiota in juvenile Chinese alligators: implications for species protection. Front Zool. 2025 Jul 29; 22(1):15.
PMID: 40731003
High-fat diet driven post-operative colon cancer recurrence is dependent upon genetic susceptibility to deoxycholic acid.
High-fat diet driven post-operative colon cancer recurrence is dependent upon genetic susceptibility to deoxycholic acid. Cancer Lett. 2025 Oct 28; 631:217943.
PMID: 40706745
Global burden and trends of hematologic malignancies based on Global Cancer Observatory 2022 and Global Burden of Disease 2021.
Global burden and trends of hematologic malignancies based on Global Cancer Observatory 2022 and Global Burden of Disease 2021. Exp Hematol Oncol. 2025 Jul 17; 14(1):98.
PMID: 40676693
EZH2 inhibitor SHR2554 enhances the anti-tumor efficacy of HDAC inhibitor Chidamide through STAT1 in T-cell lymphoma.
EZH2 inhibitor SHR2554 enhances the anti-tumor efficacy of HDAC inhibitor Chidamide through STAT1 in T-cell lymphoma. Cell Death Dis. 2025 Jul 14; 16(1):522.
PMID: 40659662
Tandem ssDNA in neutrophil extracellular traps binds thrombin and regulates immunothrombosis.
Tandem ssDNA in neutrophil extracellular traps binds thrombin and regulates immunothrombosis. Proc Natl Acad Sci U S A. 2025 Jul 08; 122(27):e2418191122.
PMID: 40608679
Building better mRNA for therapeutics.
Building better mRNA for therapeutics. Nat Biotechnol. 2025 Jul; 43(7):1058-1060.
PMID: 39313648
DNA Tweezers with Replaceable Clamps for the Targeted Degradation of Cell Membrane Proteins.
DNA Tweezers with Replaceable Clamps for the Targeted Degradation of Cell Membrane Proteins. Pharmaceutics. 2025 Jun 17; 17(6).
PMID: 40574098
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
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