Three Research Directions Unified by Adaptation

1. piRNAs as an Adaptive Genome Defense System

Adaptive challenge: Genomes are continuously challenged by internal genetic parasites, such as transposable elements and endogenous retroviruses. These elements evolve rapidly and pose a persistent threat to genome integrity and fertility.

Our view We view piRNAs as an RNA-based adaptive immune system of the germline, enabling organisms to defend their genomes against constantly changing internal threats.

We study

- How piRNAs are generated (biogenesis)

- How new piRNAs arise and existing piRNAs are lost over evolutionary time (evolution)

- What piRNAs do beyond transposon silencing (function)

We discovered that ribosomes actively guide piRNA biogenesis, revealing that the translation machinery itself can be repurposed as an adaptive RNA-processing system. This mechanism is conserved across vertebrates, indicating strong evolutionary selection.

In chickens, we showed that hosts can convert viral sequences into piRNA-producing loci, an adaptive strategy conceptually analogous to the CRISPR system in bacteria. This finding highlights how RNA-based mechanisms enable rapid adaptation to genomic threats without relying on slow DNA sequence evolution.

Adaptation principle RNA-based systems provide fast and flexible genome defense against evolving internal challenges.

2. Sperm RNA as a Medium of Environmental Memory

Adaptive challenge: Parental environments can strongly influence offspring health and development, even when DNA sequence remains unchanged.

Our view We propose that sperm RNA serves as a carrier of adaptive information across generations, linking environmental experiences in parents to phenotypic outcomes in offspring.

We demonstrated that mammalian sperm harbor thousands of intact mRNAs, many encoding ribosomal and translational components. These RNAs are selectively retained, rather than passively inherited remnants of spermatogenesis.

We study

- How environmental factors (such as toxins, diet, and metabolic state) reshape sperm RNA profiles

- How sperm RNAs influence early embryonic development

- Why some environmentally induced responses persist across generations while others are transient

Our work on heavy metal exposure in combination with metabolic disease reveals strong synergistic and transgenerational effects on kidney and metabolic health, supporting the idea that environmental adaptation—or maladaptation—can be transmitted through RNA-based mechanisms.

Adaptation principle RNA enables organisms to transmit environmental experiences to offspring without altering DNA sequence.

3. RNA Medicine as Directed Adaptation

Adaptive challenge: Many genetic and epigenetic disorders reflect failed, incomplete, or mistimed biological adaptation.

Our view We view RNA therapeutics as a form of engineered adaptation, designed to restore or enhance adaptive biological processes without permanently rewriting the genome.

We develop

- mRNA therapies to rescue male infertility

- siRNA strategies to target dominant-negative mutations

- UTR design platforms to tune RNA stability and translation efficiency

- mRNA-based vaccines and antivenom approaches

Compared with gene therapy, RNA-based medicine:

- Does not permanently alter DNA

- Can be precisely timed and spatially controlled

- Closely mimics natural, evolutionarily conserved RNA regulatory strategies

Adaptation principle RNA therapeutics are effective because evolution already uses RNA as a primary tool for biological adaptation.

Unifying Concept

Across all three directions, our work converges on a single idea:

RNA is the molecular system that enables organisms—and their offspring—to adapt to a changing world.

Genetic change represents one possible outcome of adaptation. Epigenetic inheritance represents another. Failure to adapt can lead to infertility, disease, or extinction. RNA lies at the center of all three outcomes.

By studying RNA-mediated adaptation, we aim to:

- Build next-generation biological theory, in which heredity and evolution are shaped not only by DNA sequence, but also by RNA-based inheritance and adaptive repurposing of core cellular machines such as ribosomes

- Redefine breeding and trait selection, moving beyond purely genetic models to incorporate environmentally responsive and heritable RNA states, with direct applications in poultry and animal agriculture

- Create RNA-based therapies for unmet medical needs, leveraging nature's own adaptive strategies rather than permanently rewriting the genome