• Once deemed heretical, the idea of “inheritance of acquired characteristics” is now gaining evidence from multiple species, including mammals. Studies from our lab and others now promote the idea that paternally acquired phenotypes (e.g. metabolic disorders) from environmental stressors can be encoded in the form of sperm RNAs & RNA modifications as a 'sperm RNA code' (Nat Rev Endocrinol 2019, 2020) which transmit paternal phenotypes to the offspring via shaping early embryo development (Nat Rev Genet 2016). Beyond RNA sequences and modifications, we are actively exploring RNA structures as novel epigenetic information carriers (Nat Cell Biol 2025). 
tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs) are newly discovered small non-coding RNAs with diverse functions. As critical components of the 'sperm RNA code', we showed that sperm tsRNAs/rsRNAs can act as hereditary factor that contribute to the intergenerational transmission of paternally acquired metabolic disorder. Read more

Embryo symmetry breaking

Sperm RNA code

During mammalian early embryo development, how do different lineages emerge? Are 2-cell blastomeres absolutely equal? If not, can there be even small differences at molecular levels? and if so, how do they arise at the first place and how could they get amplified to guide future cell fate? Read more
We use novel tools including SPORTS, PANDORA-seq, FUSION and mass spectrometry-based methods such as LC-MS/MS and MLC-seq to study how small RNAs derived from fragmentation of longer parental RNAs (e.g., tRNAs, rRNAs), along with their RNA modifications and responsible enzymes, dynamically regulate gene expression and cause diseases such as cancer. Read more

The RNA 'renovatio'

Latest Lab news (More news)                             
2025. 12 Glad to see the thoughtful article in Quanta Magazine on the 'Sperm RNA Code' and paternal epigenetic inheritance, featuring our decade-long efforts with many active colleagues in the field. There are immense unknowns to explore...
2025. 12 Our collaborative work with Changcheng Zhou lab  found a highly abundant hepatic tsRNA function as a regulator of cholesterol homeostasis and atherosclerosis, now published in Nature Communications. Great to see PANDORA-seq enable new biology.
2025. 10 Our collaborative work with Bruno Di Stefano Lab on RNA sequestration in biomolecular condensates and cell fates regulation is published in Nature Biotechnology. This lends support to the condensate-based cellular memory we hypothesized in Nature Cell Biology
2025. 10 Qi gave talks about 'sperm RNA code' at Nanoscience Days 2025, and new tools to explore the expanding universe of small RNAs at the University of Jyväskylä in Finland. Loved the nordic vibes - elegant simplicity
2025.9 After developing PANDORA-seq to reveal hidden small RNAs (e.g., tsRNA, rsRNAs) and SPORTS to annotate them, we now expand our toolchain with Zhou Lab, introducing FUSION, a tool robustly interprets small RNA changes even in small or 1-on-1 datasets, in Bioinformatics
2025.8 Perhaps our boldest idea, we propose a hypothetical model for RNA structural memory propagation via conformational catalysis within biomolecular condensates, and its impact on evolution and disease, published in Nature Cell Biology. The evidence awaits discovery.
2025.4 We put together a step-by-step protocol for PANDORA-seq, along with analyzing software SPORTS,  published in Nature Protocols
2025.3-4 Qi gave a seminar at Brown university, and presented at the RNA Mass Spectrometry Virtual Symposium by Weill Cornell Medicine.
2025.2 We publish a two-stage activation hypothesis explaining how abnormal small RNA biogenesis sparks autoimmune diseases via small RNA-TLR7/8 interactions in Trends in Biochemical Sciences, highlighted as Cover Story
  • We explore the expanding universe of small RNAs with new tools: PANDORA-seq opens the once hidden small RNA universe, SPORTS for quick annotatation, FUSION  for accurate statistical analyses, LC-MS/MS & MLC-seq to decipher the RNA modifications. Decoding the 'RNA code' (RNA sequence & modification) opens new functional principles, including the structure-centric views of their action, inspiring new ways of information propagation across generations (Nat Cell Biol 2025) and unlocking emerging roles in autoimmuity (Trends Biochem Sci 2025) and aging.
  • We pioneered the systematic discovery of tRNA-derived small RNAs (tsRNAs) (Cell Res 2012, Science 2016) & rRNA-derived small RNAs (rsRNAs) (Nat Cell Biol 2018) in sperm with novel tools like PANDORA-seq (Nat Cell Biol 2021); showing that sperm tsRNAs/rsRNAs and their RNA modifications act as epigenetic factors in mediating intergenerational inheritance of acquired metabolic disorders, which require the action of RNA methyltransferase Dnmt2 (Science 2016, Nat Cell Biol 2018)
  • Our discovery of abundant tsRNAs in physiological contexts such as sperm and serum, coupled with their sensitive responses to environmental stimuli and diseases, has sparkled a new wave of tsRNA research. These tsRNAs, which are evolutionarily ancient (predating miRNAs), harness their linear sequences and 3D structures to perform unexpected biological functions (Trends Biochem Sci 2021, J Biol Chem 2023), which embodies the concept of tRNA ‘renovatio’ (from Latin, meaning renewal and rebirth) (Mol Cell 2023). The artwork depicts the re-creation process of tsRNAs through the metaphor of a supernova explosion, in which the end of one stellar life cycle triggers the genesis of new stars.

The Evolving Ideas of Heredity & Hereditary Information Carriers (further read)

Exploring the expanding small RNA universe with new tools (futher read)

  • The idea of RNA ‘renovatio’ has been further accentuated by our new method PANDORA-seq (Nat Cell Biol 2021), which systematically reveals abundant existence of various types of small noncoding RNAs (sncRNAs) beyond the siRNAs/miRNA/piRNAs, including sncRNAs derived from various parental RNAs (tRNA, rRNA, snoRNA, snRNA, Y RNA, Vault RNA etc) carrying different termini and RNA modifications that are previously undetectable by using traditional small RNA-seq. This has redrawn the boundaries of the small RNA universe, heralding new directions in research (Nat Cell Biol 2022)