Yizhou Yu

What
My goal is to unravel diseases by integrating insights from the genomic, epigenomic, transcriptomics, proteomic, metabolomic, inter-organ and behavioural levels. Technological advances in both laboratory techniques and AI are enabling us to collect and analyse exponentially more data, at higher resolution.
By gaining deeper insights into human biology during health and disease, we will be able to pinpoint mechanistic biomarkers and therapeutic targets, which can be translated into personalized interventions.

How
To achieve this, I have been generating data from cellular models, animal models, patient samples and epidemiological-scale data; and analysing via AI/ML methods. This integrative approach can overcome limitations in individual modalities.

Please visit my Google Scholar page for the full list of my publications.

Parp mutations protect from mitochondrial toxicity in Alzheimer's disease

We analysed the metabolomic changes in a fly model of AD and identified a decrease of metabolites associated with nicotinamide metabolism, which is critical for mitochondrial function in neurons. We used combined results in flies and humans to show that increasing the bioavailability of NAD+ is neuroprotective.

Distinct forms of amyloid-β moderate sleep duration through NAD+-linked redox metabolism in Alzheimer’s disease

Sleep problems often appear years before Alzheimer’s disease is diagnosed, but we still don’t understand why. We discovered that people at high risk of Alzheimer’s tend to sleep less, while those with a diagnosis sleep more. We replicated these sleep patterns by expressing different forms of amyloid-β protein in animal models. We uncovered that these changes were linked to NAD+ levels and a sleep-regulating protein, hyperkinetic.

Enhancing mitochondrial one-carbon metabolism is neuroprotective in Alzheimer’s disease models

Here, we found that a specific mitochondrial process called one-carbon metabolism is disrupted in Alzheimer's disease. Boosting this pathway genetically or by supplementing with folinic acid improved mitochondrial function in both flies and cells. Human data also showed that genes involved in this pathway affect AD risk, suggesting a new treatment direction.

I an a co-founder at the International Sleep Charity!
Sleep is super important to maintain brain health. However, many factors including genetics and habitual can cause poor sleep. My role at the charity is to conduct research to find the causes for poor sleep and develop treatments to help people sleep better!