DrRaffaella Nativio
Assistant Professor in EpiAge and Neurodegeneration
Department of Brain Sciences - Faculty of Medicine
- Assistant Professor in EpiAge and NeurodegenerationDepartment of Brain Sciences - Faculty of Medicine
- Sir Michael Uren Hub, White City Campus, United Kingdom
BIO
Raffaella Nativio is an Assistant Professor in the Department of Brain Sciences at Imperial College London. Her research focuses on the epigenetic mechanisms of healthy brain ageing and neurodegeneration, with particular emphasis on cell type- and cell state-specific regulation.
She obtained a BSc and MSc in Biotechnology from the University of Rome Sapienza and a PhD in Molecular Biology from the University of Cambridge, where she investigated 3D genome conformation in genomic imprinting and associated disorders, uncovering a role for cohesin in mediating CTCF-dependent chromatin interactions. She undertook postdoctoral training with Prof. Shelley Berger at the University of Pennsylvania (Penn), following an appointment as a visiting fellow at the National Institutes of Health (NIH).
At Penn, she performed studies in human postmortem brain tissue, revealing that the epigenome of Alzheimer’s disease (AD) is distinct from healthy ageing — characterized by histone modification changes linked to loss of protective mechanisms and activation of disease-specific pathways enriched in AD GWAS SNPs. These findings underscore the potential for epigenetic therapies to alter the trajectory of ageing and neurodegeneration. She also investigated how environmental factors, such as alcohol metabolism, influence histone acetylation and memory. More recently, her research has expanded to examining the role of 3D chromatin conformation in ageing and AD.
RESEARCH SUMMARY:
The Nativio Lab investigates the epigenetic mechanisms underlying healthy brain ageing and the drivers of neurodegeneration. The lab’s goal is to identify novel epigenetic regulators—such as chromatin-modifying enzymes and transcription factors (TFs)—whose modulation promotes cellular resilience to age- and disease-related stresses while mitigating detrimental inflammatory states.
Ageing is the primary risk factor for neurodegenerative diseases, yet the underlying mechanisms remain unclear. Not all individuals develop neurodegeneration with age, suggesting that protective mechanisms are either present or activated during ageing, but may become impaired in disease. Epigenetic mechanisms, which regulate gene expression in response to environmental stimuli, play a key role in longevity, ageing, and neurodegeneration. By integrating environmental influences into the genome, chromatin regulation likely reflects the environmental contribution to disease. Moreover, many risk variants map to non-coding regulatory elements, such as enhancers, suggesting that epigenetic regulation may also mediate interactions between genetic and environmental factors.
To address these questions, the lab investigates key mechanisms of epigenetic regulation—including histone post-translational modifications (PTMs), TF regulation, and 3D genome architecture—through two complementary approaches:
1. Human postmortem brain tissue: in vivo epigenomic profiling is used to map cell type-specific differences between healthy ageing and Alzheimer’s disease (AD), thereby identifying novel pathways and candidate regulators— such as protective programs in healthy ageing that become dysregulated in AD, or disease-specific mechanisms activated in AD.
2. In vitro models: human iPSC-derived neurons, astrocytes, and microglia, as well as primary cultures, are used to model intrinsic cellular responses to ageing- and disease-related stresses. These systems enable dissection of epigenetic mechanisms that drive cell-state transitions such as senescence and reactive/activated states. In vitro models are also employed to functionally test candidate regulators identified in postmortem tissue or in stress-induced state transition models.
The lab applies a broad range of genomic and epigenomic techniques, including ChIP-seq to profile histone PTMs and TF binding, ATAC-seq to map open chromatin, RNA-seq for transcriptome profiling, Hi-C and HiChIP to characterize 3D genome conformation, and single-nucleus multi-omics to resolve cell type-specific states. Functional genomics approaches such as CRISPR interference are then used to test causal relationships between epigenetic mechanisms and cellular phenotypes.
Ultimately, the lab aims to define the epigenetic basis of healthy ageing in contrast to neurodegeneration and to establish therapeutic avenues to enhance brain resilience and promote healthy ageing. Because epigenetic modifications are reversible and context-dependent, they represent promising targets for precise therapeutic strategies.
LAB MEMBERS:
Anna Maggiore, Research Associate
Ida Bomann, PhD student
Jia Qi Chong, PhD student and Research Assistant
Rhiannon Cummins, PhD student
Chelsie X Li, PhD student (jointly supervised with Dr Di Antonio)
Yemin Lan, Bioinformatician
Caitlin Law, Research Technician
Sydney Xie, MRes student
RESEARCH OPPORTUNITIES:
The Nativio Lab is eager to hear from ambitious, science-driven postdocs and students interested in joining the group. If you would like to discuss research projects or explore fellowship or scholarship opportunities, please contact Raffaella. To apply, email your CV and a brief motivation statement.
She obtained a BSc and MSc in Biotechnology from the University of Rome Sapienza and a PhD in Molecular Biology from the University of Cambridge, where she investigated 3D genome conformation in genomic imprinting and associated disorders, uncovering a role for cohesin in mediating CTCF-dependent chromatin interactions. She undertook postdoctoral training with Prof. Shelley Berger at the University of Pennsylvania (Penn), following an appointment as a visiting fellow at the National Institutes of Health (NIH).
At Penn, she performed studies in human postmortem brain tissue, revealing that the epigenome of Alzheimer’s disease (AD) is distinct from healthy ageing — characterized by histone modification changes linked to loss of protective mechanisms and activation of disease-specific pathways enriched in AD GWAS SNPs. These findings underscore the potential for epigenetic therapies to alter the trajectory of ageing and neurodegeneration. She also investigated how environmental factors, such as alcohol metabolism, influence histone acetylation and memory. More recently, her research has expanded to examining the role of 3D chromatin conformation in ageing and AD.
RESEARCH SUMMARY:
The Nativio Lab investigates the epigenetic mechanisms underlying healthy brain ageing and the drivers of neurodegeneration. The lab’s goal is to identify novel epigenetic regulators—such as chromatin-modifying enzymes and transcription factors (TFs)—whose modulation promotes cellular resilience to age- and disease-related stresses while mitigating detrimental inflammatory states.
Ageing is the primary risk factor for neurodegenerative diseases, yet the underlying mechanisms remain unclear. Not all individuals develop neurodegeneration with age, suggesting that protective mechanisms are either present or activated during ageing, but may become impaired in disease. Epigenetic mechanisms, which regulate gene expression in response to environmental stimuli, play a key role in longevity, ageing, and neurodegeneration. By integrating environmental influences into the genome, chromatin regulation likely reflects the environmental contribution to disease. Moreover, many risk variants map to non-coding regulatory elements, such as enhancers, suggesting that epigenetic regulation may also mediate interactions between genetic and environmental factors.
To address these questions, the lab investigates key mechanisms of epigenetic regulation—including histone post-translational modifications (PTMs), TF regulation, and 3D genome architecture—through two complementary approaches:
1. Human postmortem brain tissue: in vivo epigenomic profiling is used to map cell type-specific differences between healthy ageing and Alzheimer’s disease (AD), thereby identifying novel pathways and candidate regulators— such as protective programs in healthy ageing that become dysregulated in AD, or disease-specific mechanisms activated in AD.
2. In vitro models: human iPSC-derived neurons, astrocytes, and microglia, as well as primary cultures, are used to model intrinsic cellular responses to ageing- and disease-related stresses. These systems enable dissection of epigenetic mechanisms that drive cell-state transitions such as senescence and reactive/activated states. In vitro models are also employed to functionally test candidate regulators identified in postmortem tissue or in stress-induced state transition models.
The lab applies a broad range of genomic and epigenomic techniques, including ChIP-seq to profile histone PTMs and TF binding, ATAC-seq to map open chromatin, RNA-seq for transcriptome profiling, Hi-C and HiChIP to characterize 3D genome conformation, and single-nucleus multi-omics to resolve cell type-specific states. Functional genomics approaches such as CRISPR interference are then used to test causal relationships between epigenetic mechanisms and cellular phenotypes.
Ultimately, the lab aims to define the epigenetic basis of healthy ageing in contrast to neurodegeneration and to establish therapeutic avenues to enhance brain resilience and promote healthy ageing. Because epigenetic modifications are reversible and context-dependent, they represent promising targets for precise therapeutic strategies.
LAB MEMBERS:
Anna Maggiore, Research Associate
Ida Bomann, PhD student
Jia Qi Chong, PhD student and Research Assistant
Rhiannon Cummins, PhD student
Chelsie X Li, PhD student (jointly supervised with Dr Di Antonio)
Yemin Lan, Bioinformatician
Caitlin Law, Research Technician
Sydney Xie, MRes student
RESEARCH OPPORTUNITIES:
The Nativio Lab is eager to hear from ambitious, science-driven postdocs and students interested in joining the group. If you would like to discuss research projects or explore fellowship or scholarship opportunities, please contact Raffaella. To apply, email your CV and a brief motivation statement.
FACULTY
- Faculty of Medicine
POSITION NAME
- Assistant Professor in EpiAge and Neurodegeneratio