projects

The Finelli group explores cellular resilience at different levels through four interconnected research pillars:

Molecular resilience

Dr Finelli was one of the early pioneers in the investigation of a family of proteins called the ‘TLDc proteins‘, and discovered their protective role in mammalian neurons. Combining proteomics with protein-protein interaction assays, we investigate how interactions between the TLDc proteins and their binding partners regulate neuronal resilience and survival. We aim to uncover protective mechanisms that may be disrupted in neurological diseases caused by defective mutated TLDc proteins.

Metabolic resilience

We investigate how neurons and astrocytes maintain metabolic homeostasis and adapt to disease-associated stress, focusing on redox balance and interconnected metabolic pathways. Using metabolomics, we seek to identify the metabolic vulnerabilities and adaptive mechanisms that determine neuronal resilience, in particular in ageing and neurodegenerative diseases such as Alzheimer’s disease.

Cellular resilience

We explore how neuronal survival depends not only on intrinsic protective mechanisms but also on the support provided by neighbouring cells, particularly astrocytes, and by the extracellular environment. We investigate how miscommununication between cells of the brain (e.g., neurons and astrocytes), and between organs (e.g., brain-lung crosstalk) contributes to neurological conditions. We aim to uncover whether restoring normal cell-cell communication can preserve neuronal function.

Reprogramming resilience

We aim to move beyond describing neurodegenerative pathology towards identifying ways to restore the protective mechanisms that fail in disease. Integrating patient-derived iPSC models, multi-omics, drug screening, and machine learning, we seek to discover disease signatures and actionable therapeutic targets, and develop strategies to strengthen neuronal resilience.

Image credit: Banner: Robert Markus; Illustrations: ChatGPT / OpenAI.