Garaycoechea: Metabolic mutagenesis

Back to research groups

The Garaycoechea group studies how the interaction between metabolism and DNA repair leads to mutation in a physiological setting.

DNA carries the instructions of life, but is also under constant attack. The resulting damage, if not repaired, leads to mutation and disease. Common environmental mutagens include sunlight and cigarette smoke, but the integrity of DNA is also threatened by chemicals produced by our own body. Our group wants to understand what are the metabolites that arise within cells that damage DNA, and the consequences of this damage. Particularly, we are interested in understanding the maintenance of genome stability in stem cells, the rare cell populations responsible for tissue maintenance.

Key publicationsView all publications

Aldehyde-driven transcriptional stress triggers an anorexic DNA damage response

Mulderrig L, Garaycoechea JI, Tuong ZK, Millington CL, Dingler FA, Ferdinand JR, Gaul L, Tadross JA, Arends MJ, O'Rahilly S, Crossan GP, Clatworthy MR, Patel KJ

Nature. Dec;600(7887):158-163

Download|2021

Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells

Garaycoechea JI, Crossan GP, Langevin F, Mulderrig L, Louzada S, Yang F, Guilbaud G, Park N, Roerink S, Nik-Zainal S, Stratton MR, Patel KJ

Nature 11;553(7687):171-177

Download|2018

Endogenous formaldehyde is a hematopoietic stem cell genotoxin and metabolic carcinogen

Pontel LB, Rosado IV, Burgos-Barragan G, Garaycoechea JI, Yu R, Arends MJ, Chandrasekaran G, Broecker V, Wei W, Liu L, Swenberg JA, Crossan GP, Patel KJ

Mol Cell 1;60(1):177-88

Download|2015

Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function

Garaycoechea JI, Crossan GP, Langevin F, Daly M, Arends MJ, Patel KJ

Nature. Sep 27;489(7417):571-5

Download|2012

XPF-ERCC1 protects liver, kidney and blood homeostasis outside the canonical excision repair pathways

Mulderrig L, Garaycoechea JI

PLoS Genet. 2020 Apr 9;16(4):e1008555

Download|2020

Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements

Luquette LJ, Miller MB, Zhou Z, Bohrson CL, Zhao Y, Jin H, Gulhan D, Ganz J, Bizzotto S, Kirkham S, Hochepied T, Libert C, Galor A, Kim J, Lodato MA, Garaycoechea JI, Gawad C, West J, Walsh CA, Park PJ

Nat Genet. Oct;54(10):1564-1571

Download|2022

Group leader

Juan Garaycoechea

Juan Garaycoechea began his scientific career in Argentina, where in 2010 he obtained a first-class degree in Biotechnology from Universidad Nacional de Quilmes. He was then awarded the César Milstein scholarship to carry out his PhD studies at the MRC Laboratory of Molecular Biology (LMB), in Cambridge, UK. At the end of his studies, Juan was awarded a Junior Research Fellowship by King’s College, Cambridge to support his post-doctoral research at the LMB. He is a group leader at the Hubrecht Institute from October 2018, where he studies the metabolites that damage DNA and how this leads to mutation in a physiological context.