Research Projects
Genes, Chromatin and Rare Neurodevelopmental Disorders
Our laboratory investigates the complex interplay between genetic alterations, cellular homeostasis, and biological sex in rare neurodevelopmental disorders (NDD). We employ multidisciplinary approaches to understand disease mechanisms and identify potential therapeutic and diagnostic strategies for conditions with no interventional protocols.
Plasticity and Resilience of developmental processes
Although rare neurodevelopmental disorders have various causes, many genetic mutations converge, much like light passing through a prism, primarily affecting neurons and the immune system. Using human disease models, we study how these seemingly unrelated genetic changes ultimately lead to similar developmental bottlenecks, often through adaptive mechanisms such as paralogue compensation (e.g. Sm proteins, MPRL) and metabolic rewiring. By understanding how diverse genetic causes produce common cellular responses, we aim to develop treatments that target these shared effects rather than each individual genetic ‘entry point’.
Chromatin Dysfunction in NDD
Collectively 58 million people worldwide are diagnosed with rare neurodevelopmental disorders leading to intellectual disability and failure to thrive. The most enriched class of causative mutations are found in genes belonging to the chromatin machinery, exemplified by the Basilicata-Akhtar syndrome (MRXSBA). We explore how chromatin factors extend beyond their gene-regulating roles to affect processes outside the nucleus. Our research examines the critical communications between the nucleus and other cellular compartments, including the plasma membrane, mitochondria, endoplasmic reticulum, and lysosomes. These organelle networks maintain cellular homeostasis and enable rapid responses to environmental changes through direct material exchange. When chromatin architecture is disrupted, it triggers cascading effects throughout various cellular compartments, compromising homeostatic molecular dialogues. Why and how these ubiquitous structure alterations impinge so distinctly on neuronal dysfunctions remains a hidden nexus that our research aims to illuminate.
The complex balance of the Sex Chromosomes in Development and Disease
A striking feature of neurodevelopmental disorders is their pronounced sex bias, with males typically affected at least twice as frequently as females. This pattern exists alongside females generally exhibiting greater susceptibility to autoimmune conditions. In our laboratory, we study how biological sex influences embryonic development and disease progression through both genetic and hormonal mechanisms. By understanding how sex chromosome dosage influences differential cellular responses in male and female cells, we aim to develop more personalized approaches to treating disorders that account for sex specific differences in pathophysiology.
Are you interested in our research?
We are always happy to welcome new members to our team. Please send us your application package as a single PDF containing your CV, career goals, and a statement explaining why you would like to join our science team.
AI Policy of the lab: AI assistance is welcome for tasks such as proofreading, but you must clearly indicate where it was used. Primarily AI-generated applications will be automatically discarded without feedback.