Contact information
biography
I graduated in Biology from the University of Minho (Portugal), followed by research training at the Academic Medical Centre (Netherlands) and the Karolinska Institute (Sweden). I completed a PhD at the University of Oxford in 2014 where I developed new human stem-cell models of disease to elucidate the role of genetic variants associated with Parkinson’s disease.
I then moved to the Wellcome Sanger Institute to develop and implement a range of high-throughput and deep phenotyping tools including single-cell lipidomics, genome-wide CRISPR-Cas9 screens, and single-cell transcriptomics. I expanded this work at the UK Dementia Research Institute at the University of Cambridge focusing on the identification of novel targets for neurodegeneration.
I returned to the University of Oxford in 2022 and was awarded an Alzheimer’s Society Dementia Research Leader Fellowship to start my own research program in autumn 2023 at Department of Physiology, Anatomy and Genetics and the Kavli Institute.
Hugo Fernandes
Group Leader
- Alzheimer’s Society Dementia Research Leader Fellow
RESEARCH SUMMARY
I am interested in understanding the molecular mechanisms underlying selective neuronal vulnerability in dementia and neurodegeneration. My goal is to identify novel disease targets that could lead to effective therapeutic interventions to improve patients' quality of life.
I use induced pluripotent stem cells (iPSCs) to establish novel neuronal models of disease (disease-in-a-dish) to identify and modify the early mechanisms of cellular dysregulation. Current projects are focused on:
- Impaired lipid metabolism in dementia. Exploring the molecular mechanism underlying lipid perturbations in neuronal models of dementia in the context of selective neuronal vulnerability. Focusing on cholesterol biosynthesis, Lipid Droplet homeostasis and fatty acid metabolism.
- Novel drivers of neuronal resilience. Identification of novel genes that mediate neuronal vulnerability and resilience using arrayed and pooled CRISPR screens (genome-wide and targeted libraries). Particular focus on lipid dysregulation, ER stress and lysosomal function.
- Functional cellular heterogeneity. Dissecting neuronal diversity and heterogeneity in neurodegeneration at scale, by developing and implementing a range of high-throughput and deep phenotyping tools including single-cell lipidomics and single-cell transcriptomics. By implementing these complementary approaches, I aim at identifying critical targets for neurodegeneration with future clinical applications.
I am a strong advocate for interdisciplinary and collaborative efforts as the path for innovation and cutting-edge research. Get in touch if you would like to discuss possible collaborations or simply to chat about exciting research ideas!
Key publications
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Changes in Oxidised Phospholipids in Response to Oxidative Stress in Microtubule-Associated Protein Tau (MAPT) Mutant Dopamine Neurons.
Journal article
Bradford X. et al, (2024), Antioxidants (Basel, Switzerland), 13
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Commentary: Parkinson disease-linked GBA mutation effects reversed by molecular chaperones in human cell and fly models
Journal article
Fernandes HJR. et al, (2016), Frontiers in Neuroscience, 10
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Mitochondrial and Endoplasmic Reticulum Stress Trigger Triglyceride Accumulation in Models of Parkinson's Disease Independent of Mutations in MAPT.
Journal article
Fernandes HJR. et al, (2023), Metabolites, 13
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Single-Cell Transcriptomics of Parkinson's Disease Human In Vitro Models Reveals Dopamine Neuron-Specific Stress Responses.
Journal article
Fernandes HJR. et al, (2020), Cell reports, 33
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Cellular α-synuclein pathology is associated with bioenergetic dysfunction in Parkinson’s iPSC-derived dopamine neurons
Journal article
Zambon F. et al, (2019), Human Molecular Genetics, 28, 2001 - 2013
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Physiological Characterisation of Human iPS-Derived Dopaminergic Neurons
Journal article
Hartfield EM. et al, (2014), PLoS ONE, 9, e87388 - e87388
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Felodipine induces autophagy in mouse brains with pharmacokinetics amenable to repurposing.
Journal article
Siddiqi FH. et al, (2019), Nature communications, 10
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Development and Application of High-Throughput Single Cell Lipid Profiling: A Study of SNCA-A53T Human Dopamine Neurons.
Journal article
Snowden SG. et al, (2020), iScience, 23
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CRISPR-Cas9 genetic screen leads to the discovery of L-Moses, a KAT2B inhibitor that attenuates Tunicamycin-mediated neuronal cell death
Journal article
Pavlou S. et al, (2023), Scientific Reports, 13
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Variant-specific effects of GBA1 mutations on dopaminergic neuron proteostasis.
Journal article
Onal G. et al, (2024), Journal of neurochemistry, 168, 2543 - 2560
Recent publications
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Variant-specific effects of GBA1 mutations on dopaminergic neuron proteostasis.
Journal article
Onal G. et al, (2024), Journal of neurochemistry, 168, 2543 - 2560
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Changes in Oxidised Phospholipids in Response to Oxidative Stress in Microtubule-Associated Protein Tau (MAPT) Mutant Dopamine Neurons.
Journal article
Bradford X. et al, (2024), Antioxidants (Basel, Switzerland), 13
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CRISPR-Cas9 genetic screen leads to the discovery of L-Moses, a KAT2B inhibitor that attenuates Tunicamycin-mediated neuronal cell death
Journal article
Pavlou S. et al, (2023), Scientific Reports, 13
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Post-translational proteomics platform identifies neurite outgrowth impairments in Parkinson’s disease GBA-N370S dopamine neurons
Journal article
Bogetofte H. et al, (2023), Cell Reports, 42, 112180 - 112180
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Mitochondrial and Endoplasmic Reticulum Stress Trigger Triglyceride Accumulation in Models of Parkinson's Disease Independent of Mutations in MAPT.
Journal article
Fernandes HJR. et al, (2023), Metabolites, 13
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Surface charge and dynamic mechanoelectrical stimuli improves adhesion, proliferation and differentiation of neuron-like cells.
Journal article
Marques-Almeida T. et al, (2022), Journal of materials chemistry. B, 11, 144 - 153
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A novel post-translational proteomics platform identifies neurite outgrowth impairments in Parkinson’s diseaseGBA-N370Sdopamine neurons
Preprint
Bogetofte H. et al, (2021)
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MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development.
Journal article
Parada GE. et al, (2021), Genome biology, 22
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Development and Application of High-Throughput Single Cell Lipid Profiling: A Study of SNCA-A53T Human Dopamine Neurons.
Journal article
Snowden SG. et al, (2020), iScience, 23
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Single-Cell Transcriptomics of Parkinson's Disease Human In Vitro Models Reveals Dopamine Neuron-Specific Stress Responses.
Journal article
Fernandes HJR. et al, (2020), Cell reports, 33