Since establishing our research program in 2016, the Berchowitz Lab has investigated multiple interrelated processes—post-transcriptional gene regulation, transposable element domestication and defense, reproductive aging, and biomolecular condensate function—to understand how cells preserve genomic integrity and transmit genetic information across generations. To address these questions, we integrate classical and cutting-edge genetic approaches in yeast and mouse models with cell and molecular biology, biochemistry, computational analysis, and reproductive biology. Our long-term goal is to translate these discoveries into therapies for infertility and proteostasis-related disorders.

A major focus of our work is the domestication of retrotransposon‐derived genes in reproduction. In budding yeast, we uncovered that Ty3 retrotransposons hijack meiotic transcription factor binding sites to ensure their expression during gametogenesis, while meiotic cells deploy amyloid‐like condensates of RNA‐binding proteins to suppress transposon mRNAs. Extending these themes to mammals, we identified two viral‐capsid–derived genes, PNMA1 and PNMA4, whose expression declines with age and whose loss accelerates fertility decline in mice. Strikingly, PNMA proteins self‐assemble into capsid‐like particles that package RNA, suggesting a novel, naturally evolved mechanism of mRNA transport that supports reproductive longevity.

We also investigate the function and regulation of biomolecular condensates in translational control. Working with the meiotic RNA‐binding protein Rim4, we demonstrated that its transition into detergent‐resistant, fibrillar condensates is essential for message‐specific repression during meiosis—a mechanism conserved in the murine translational regulator DAZL. By dissecting the sequence and structural features that drive condensate formation, we revealed how condensate architecture dictates repressive capacity. Moreover, in collaboration with colleagues examining bacterial pathogenesis, we discovered that Fusobacterium nucleatum secretes an amyloid‐like adhesin, FadA, which scaffolds biofilm formation and enhances tumor colonization.

Building on our studies of condensate assembly, we have elucidated the cellular mechanisms that disassemble and clear physiological amyloids. We showed that phosphorylation of Rim4’s intrinsically disordered region triggers its disassembly and proteolysis, coordinated by specific kinases, and that yeast 14-3-3 proteins bind the phosphorylated form to facilitate clearance. These findings prompted us to characterize broader translational control circuits in meiosis: we uncovered that the Ime2 kinase times the meiotic divisions by regulating Rim4 stability and the translation of key mRNAs. Finally, applying these principles to human disease, we demonstrated that chemical inhibition of casein kinase 1δ selectively disrupts protein synthesis in lymphoma cells, pointing to a promising therapeutic strategy. Ultimately, we aspire to develop a unified framework that elucidates the interplay among genome integrity, reproductive health, and proteostasis.