ProfessorJuanma Vaquerizas

Chair in Developmental and Regulatory Genomics

Institute of Clinical Sciences - Faculty of Medicine

RESEARCH

My laboratory investigates how genome regulation is established, remodelled and interpreted during development. We are particularly interested in the relationship between chromatin architecture, transcriptional control and cell fate, and in the extent to which genome organisation actively instructs developmental transitions or provides a regulatory framework for them.

 

A major focus of our work is the emergence of three-dimensional genome architecture in early embryos. Using low-input chromatin conformation methods developed in the lab, including Pico-C, we have shown that genome organisation arises earlier and in a more ordered manner than previously appreciated. In Drosophila embryos, pioneer factors such as Zelda and GAF help establish chromatin loops before widespread genome activation, revealing a modular logic through which architecture is built during the earliest stages of development.

 

We also study epigenetic reprogramming in the germline. Our recent work has shown that the transition of primordial germ cells to gametogenesis is accompanied by large-scale reorganisation of the genome in three dimensions, including chromosome separation, centromere repositioning and the loss of topological domains and loops. These findings suggest that germ cell commitment involves not only classical epigenetic resetting, but also extensive erasure and rebuilding of genome architecture.

 

A complementary line of research in the lab investigates genome regulation in human spermatogenesis. By integrating single-nucleus multiomics with spatial transcriptomics of human testis, we are building regulatory maps of germline and somatic cell states, identifying candidate regulators of sperm development, and linking infertility-associated non-coding variation to enhancers and target genes in their cellular context.

 

We are also interested in the developmental and evolutionary impact of transposable elements. Using vertebrate models such as zebrafish, we investigate when and where transposable elements are expressed during embryogenesis, how they are distributed across genomes, and how they may contribute to the emergence of new regulatory programmes.

 

Across all of these questions, we combine wet-lab and computational innovation. In addition to generating high-resolution functional genomics data, we build analytical frameworks to compare chromatin contact maps, identify structural changes and infer regulatory mechanisms from complex genomic datasets. This combination of experimental depth and computational method development is central to how we study genome regulation.