Fernandes Group

To address this, we are currently focusing on the role of lipids on the regulation of selective neuronal vulnerability in Alzheimer’s and Parkinson’s disease using human iPSC-models, genetic CRISPR screens and single-cell multi-omics analyses.

FUN Lab

Fundamental

Understudied

Neurodegeneration

Lab

Lipid homeostasis is essential for cellular function. Lipids are fascinating and complex molecules that represent over 50% of the adult human brain dry weight, and are dysregulated with ageing and dementia. However, the impact of lipid alterations in human neurons in dementia is still poorly understood. Supported by our recent findings that challenge previous concepts in the field, we hypothesize that lipids are key driving factors in dementia-associated neuronal loss.

The goal in our lab is to identify novel disease targets that could lead to effective therapeutic interventions to improve patients' quality of life.  We use induced pluripotent stem cells (iPSCs) to establish advanced neuronal models of disease (disease-in-a-dish) to identify and modify the early mechanisms of cellular dysregulation.

Current projects in our lab are focused on:

• Understanding impaired lipid metabolism in dementia. Exploring the molecular mechanism underlying lipid perturbations in neuronal models of dementia in the context of selective neuronal vulnerability. Focus 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.

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, if you would like to join our team or simply chat about exciting research ideas!

Previous Members

• Marialuisa Testa (visiting PhD student)
• Jatin Sharma (Master’s student)