Focus areas
Research in Dr. Wei's Epigenomics of Metabolic Diseases Lab at Mayo Clinic focuses on epigenetic regulation of metabolic diseases and inflammatory diseases.
- Epigenetic mechanisms of nuclear hormones in metabolism and inflammation. Rapid and chronic molecular responses are induced when pancreatic islets are exposed to adverse conditions. Although these responses are well studied at protein and transcriptional levels, the molecular underpinnings of chromatin dynamics in response to metabolic and inflammatory challenges in islets and diabetes pathogenesis are largely unclear. Dr. Wei's laboratory is investigating the fundamental mechanisms of a novel hormone-induced epigenetic switch that mediates beta cell anti-inflammatory responses in diabetes. The lab also explores the therapeutic potential of the synergistic potentiation of hormone receptors by modulating cellular metabolites and the chromatin environment in diabetes, aging and inflammation.
- Epigenetic modulation of glucocorticoid signaling in inflammation and circadian function. Glucocorticoids are part of a class of steroids that acts to calm immune system activity. Because of this, they are used for conditions such as arthritis, asthma, flare-ups of multiple sclerosis or as part of cancer treatments. Dr. Wei's laboratory recently identified a new approach to boosting the action of steroids by modulating the epigenetic co-factors of glucocorticoid receptors in macrophages. The team continues to examine the molecular underpinnings of this epigenetic regulation and determine the function of epigenetic modulators in enhancing glucocorticoid action in multiple inflammatory disease models. Currently, the team is collaborating with Aleksey Matveyenko, Ph.D., to dissect the beneficial and pathophysiological roles of glucocorticoids in circadian islet function.
- Multi-omic dissection of enhancer heterogeneity in the pancreas. The ability to profile distinct transcriptomic and epigenomic features at the resolution of a single cell has transformed the understanding of tissue organization and heterogeneity. Dr. Wei's lab is combining various multi-omic approaches and computational platforms to determine the transcriptomic and epigenetic heterogeneity in mouse and human pancreases at the single-cell level. The goal is to define the physiological and pathological roles of tissue heterogeneity, identify functional connection of diabetic genome-wide association study variants to islet function, and identify novel targets for therapeutic applications.
- Cross talk between pancreatic islets and their microenvironment. A major cause of islet dysfunction is inflammatory and metabolic signaling from the islet microenvironment. Using genomics, single-cell profiling, proteomics and mouse genetic models, Dr. Wei's group is exploring how paracrine signals — sensed by nuclear hormone receptors and gated by the balance between permissive and repressive chromatin remodelers — transform the chromatin landscape and induce functional response in residential innate immune cells, fibroblasts and pancreatic endocrine cells.
- Novel epigenetic regulators in metabolic diseases and chronic inflammation. The epigenome of dysfunctional beta cells is shaped by dysregulation of multiple chromatin regulators. To identify novel factors involved in maintaining islet endocrine cell function and survival in stressed conditions, Dr. Wei's lab is combining genome-wide CRISPR screening with 3D stem cell-differentiated, human isletlike organoids to discover novel chromatin regulators in the mediation of cellular dysfunction and inflammatory response. The comprehensive and integrated datasets such as epigenetic changes, including histone modification, chromatin accessibility and 3D long-range interactions, will likely establish the epigenetic landscape of beta cell dysfunction.