Links to Cardiometabolic Disease

What are the molecular links between circadian rhythms and metabolism?
How does insomnia contribute to development of cardio-metabolic disease?
How does the MTNR1B diabetes risk gene link circadian rhythms to type 2 diabetes?

What are the molecular links between circadian rhythms and metabolism?
How does insomnia contribute to development of cardio-metabolic disease?
How does the MTNR1B diabetes risk gene link circadian rhythms to type 2 diabetes?

An estimated 5-12 million Americans use melatonin, a hormone naturally produced during the biological night, to treat sleeping problems. Interestingly, variants in a melatonin receptor, MTNR1B are associated with a risk of type 2 diabetes. Furthermore, ~10% of working adults are shift-workers with increased risk of type 2 diabetes. Precise mechanisms linking shift work, melatonin, and timing of food intake on diabetes prevention and control is unknown. Our research aims to inform interventions and therapeutics for vulnerable populations of late-night eaters, shift workers or users of melatonin as a sleep-aid that are at increased risk for type 2 diabetes.

Projects

Dissecting causal role of insomnia in cardiovascular disease

This project aims to identify genes and pathways at GWAS loci for insomnia symptoms in humans, test the consequence of loss-of-function of Drosophila orthologs on sleep and cardiac function, and test the impact of perturbed sleep on cardiovascular function in humans and Drosophila.

Linking circadian system and type 2 diabetes through melatonin and receptor variation

This recall by genotype study aims to test the impact of melatonin and MTNR1B variation on regulation glucose regulation in a highly controlled in-laboratory setting and ex vivo in pancreatic islets.

SHIFT Study – Impact of melatonin, food timing, and receptor variant on type 2 diabetes

This project aims to test the impact of melatonin and MTNR1B variation on glucose control and risk of type 2 diabetes in an observational study of night shift workers and natural late-night eaters.

Genetics of chronotype and impact on metabolic disease

The project aims to define the genetic basis of subjectively and objectively assessed chronotype, characterize the functional molecular, cellular, and physiologic consequences of causal genes, and variants, and dissect shared genetic relationships between chronotype and metabolic disease outcomes.

Multi-omics for precision medicine in preeclampsia

This project aims to discover common and rare variants for preeclampsia, identify molecular pathways altered before clinically defined disease using multi-omics analysis, and use PE polygenic scores to predict maternal morbidity and future maternal cardiovascular health.