Dr. Raquel Fueyo: «Impact of endogenous retroviruses on early human development»

Fecha: Viernes, 8 de mayo

Ponente/Speaker: Dra. Raquel Fueyo

Max Planck Institute for Molecular Genetics (MPIMG)

Título/Title: “Impact of endogenous retroviruses on early human development”

Lugar y hora: Salón de Actos de GENyO a las 12:00h.

Contacto: Sara R. Heras: sara.rodriguez@genyo.es

Resume: The human genome is composed of nearly 50% transposable elements. In contrast to protein-coding genes, these elements show remarkable diversity between species, hinting at potential roles in shaping species-specific functions. Human embryo models now offer the opportunity to study human-specific regulatory features in early development. Some of those features are likely mediated by endogenous retroviruses, a family of transposable elements of particular interest due to their capacity to act as cis-regulatory elements. One family of endogenous retroviruses, HERVK LTR5Hs, is restricted to hominoids and displays robust activation in human blastocysts. Here, we used human blastoids—a 3D model of the blastocyst stage—to dissect the developmental function of HERVK. Disruption of HERVK activity impairs blastoid development and alters lineage specification, underscoring its importance in human preimplantation. Mechanistically, we have identified a single human-specific LTR5Hs insertion functioning as an enhancer for the ZNF729 gene, a primate-restricted KRAB zinc-finger transcription factor. ZNF729 preferentially binds GC-rich motifs and regulates genes belonging to fundamental cellular functions in naïve pluripotency, a counterintuitive finding given the evolutionary young nature of the LTR5Hs element and the ZNF729 gene. Collectively, our study reveals a key role for HERVK in human preimplantation and illustrates how ERVs have rewired gene regulatory networks in a species-specific fashion during evolution.

CV: I did my PhD at the IBMB in Barcelona in the lab of Marian Martinez Balbas. There, I studied the molecular mechanisms driving enhancer activation in neurogenesis, with a focus on the histone demethylase JMJD3, which counteracts the Polycomb complex removing H3K27me3. For this PhD work, I got the «Premio Extraordinario de Doctorado». Then I moved to Stanford for my postdoc in Joanna Wysocka’s lab. There, I investigated the function and regulation of endogenous retroviruses, a topic which is now the main focus of my lab. For my postdoc work, I got an EMBO fellowship and a Cancer Research Institute Fellowship. In 2023, I was awarded with the Leading Edge award which recognizes outstanding women in the biomedical sciences. In 2025, I got a fully funded Group Leader position at the Max Planck Institute for Molecular Genetics. I started my lab in December 2025.

At Stanford, I study how interactions between CAR-T cells and the tumor microenvironment (TME) drive therapeutic failure in solid tumors, and I established the preclinical models needed to interrogate these mechanisms. My current work dissects how intrinsic CAR-T engineering strategies differentially remodel the tumor immune microenvironment in pediatric solid tumors. To enable clinically relevant testing platforms, I collaborate with Dr. Calvin Kuo’s lab to develop advanced 3D tumor immune organoid systems, highlighting patient-derived tumor immune organoids as a powerful approach to model immune–tumor interactions and predict responses to immunotherapies. In July 2025, I received the Kite–Gilead Early Career Award in Cell Therapy Research, supporting my transition toward independence and my current role as a Faculty Instructor at Stanford University.