Richa Saxena, PhD

Institution: Massachusetts General Hospital
Research: Genetic basis of sleep, circadian rhythms and links to metabolic disease
Grants & Publications: Harvard Catalyst
Categories: MGH

My research laboratory focuses on discovery of genes and pathways underlying sleep and circadian rhythm disorders and investigates their mechanistic links with type 2 diabetes. We aim to chart a course from genetic discoveries to biological, physiologic, and clinical insights relevant to diagnosis and treatment of sleep disorders and related cardio-metabolic disease.

Illuminating the genetic and molecular basis of sleep and circadian rhythm traits and their link to cardio- metabolic disease. Our lab aims to understand the molecular basis of sleep and circadian rhythm behaviors and disorders by defining the genetic architecture, testing gene function in model organisms, and exploring shared biological pathways between these traits and cardio-metabolic disease. We have discovered hundreds of common genetic loci for morningness/eveningness preference, insomnia, sleep duration, daytime napping, and daytime sleepiness, and we find substantial heterogeneity and genetic overlap with neuropsychiatric and cardio-metabolic disease. Mendelian randomization studies suggest that insomnia contributes in a causal way to risk of type 2 diabetes. Our work has opened up novel lines of investigation and promises to yield important fundamental and translational insights and putative therapeutic targets for sleep and circadian disorders with relevance to multiple diseases.

Impact of Melatonin, MTNR1B diabetes risk gene and food timing on glucose tolerance. An estimated 5-12 million Americans use melatonin to treat sleeping problems and ~10% of working adults are shift-workers with increased diabetes risk, but the precise effect of melatonin, and its interaction with food intake on diabetes prevention and control is unknown. We found that variation in the melatonin receptor 1b gene (MTNR1B) and core clock gene cryptochrome 2 (CRY2) influence glycemic traits, implicating circadian rhythm pathways as important in glucose homeostasis and T2D. Our recent collaborative physiologic studies suggest that night eating at a time when melatonin levels are high impairs glucose tolerance, particularly in carriers of the MTNR1B risk allele. This may impact vulnerable populations of late-night eaters, shift workers or users of melatonin as a sleep-aid. We have ongoing follow-up genotype-targeted physiologic and in-vitro human pancreatic islet studies as well as epidemiologic studies to further explore mechanisms by which MTNR1B receptor variation increases risk of type 2 diabetes.