Mertens Lab
Research
Human aging in neurons
Direct neuronal conversion preserves donor-age biology, whereas iPSC reprogramming resets it. This is important, because age is the strongest risk factor for Alzheimer’s disease and many other neurodegenerative disorders. Animal models don’t age like humans, and iPSCs erase age-related features that drive disease. Our lab studies how human biological aging changes neuronal biology - destabilizes cell identity, resilience, and vulnerability. We are not only interested in what goes wrong in disease, but why some neurons remain resilient for decades while others fail.
We use direct neuronal conversion to generate induced neurons, or iNs, from patient fibroblasts, because iNs retain aging-associated signatures that are often lost in iPSC-based models. We combine this model with advanced human post-mortem and other patient-derived biosamples, as well as rejuvenated iPSC models. This gives us a uniquely powerful system for studying adult brain disease in human cells, especially in the context of sporadic AD and other age-related disorders. By comparing iNs with iPSC-derived neurons, we can isolate what donor age contributes to neuronal function and dysfunction, and by comparing to human brain tissue, such as single cell data, we can anchor or findings in human patient brain reality.
Induced neurons from patient skin cells
A major goal of the lab is to understand how neurons maintain their identity over time, and how aging destabilizes that identity. We focus on mechanisms such as epigenetic drift, metabolic states, and protein and RNA regulation. For example, neuronal aging is closely linked to metabolism, including mitochondrial function and many important metabolites that regulate of cell resilience and identity. We study how metabolic rewiring can impact epigenetic, protein and RNA biology and weaken neuronal resilience and promote degeneration in aging and disease. This research theme connects basic aging biology and neurodegeneration research to broader principles of oncometabolism, stress resistance, and survival biology.
Cell identity control
Our lab uses human iNs as a discovery platform to uncover how aging and disease risk factors change neuronal biolgy. Because iNs retain donor-age features, we can identify disease mechanisms in a human adult-like context and then test whether candidate pathways can be modulated to restore neuronal function and resilience. This creates a direct path from mechanism discovery to target validation and therapeutic testing in the same human model system. We also use the iN model and flag-post phenotypes to test interventions directly in human neurons, which makes the iN model valuable for both mechanistic studies and translational screening.
Age-equivalent patient-specific neuronal platform for therapeutic testing