Research in Dr. Wei's Epigenomics of Metabolic Disease Lab at Mayo Clinic is focused on epigenetic regulation of metabolic disorders and inflammatory diseases.
- Signal-dependent epigenomic dynamics in diabetes. 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 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 and exploring the therapeutic potential of the synergistic modulation of hormone receptors and the chromatin environment in diabetes.
- 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, the Wei lab is combining genome-wide CRISPR screening with 3D stem cell-differentiated human islet-like organoids to discover novel chromatin regulators in the mediation of cellular dysfunction and inflammatory response. The comprehensive and integrated data sets such as epigenetic changes, including histone modification, chromatin accessibility and 3D long-range interactions, will establish the epigenetic landscape of beta cell dysfunction.
- Crosstalk 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 microenvironment 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 and pancreatic endocrine cells.
- Epigenetic modulation of glucocorticoid signaling in inflammation. Because, as a class, steroids such as glucocorticoid act to calm immune system activity, they are used for conditions such as arthritis, asthma, flair-ups of multiple sclerosis, or as part of cancer treatments. The laboratory of Dr. Wei recently identified a new approach to boosting the action of steroids by modulating the epigenetic co-factors of glucocorticoid receptor in macrophages. The team will continue 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. Given the significance of inflammation and steroids in a wide range of diseases, this finding may have broad implications in metabolic disorders and systemic inflammatory diseases.
- Developing next generation multi-omic platforms to interrogate tissue heterogeneity. The ability to profile distinct transcriptomic and epigenomic features at the resolution of single cell has transformed our understanding of tissue organization and heterogeneity. Dr. Wei's lab is combining multi-omic next-generation sequencing approaches and computational platforms to characterize diverse cellular population in the pancreas at the single-cell level. The goal is to define the physiological and pathological role of tissue heterogeneity, and to identify novel targets for therapeutic applications.