The laboratory of Zong Wei, Ph.D., focuses on creating novel models to study diabetes, metabolism and inflammation, and to identify therapeutic targets in metabolic and inflammatory diseases. Using both human stem cell-differentiated organoids and mouse models, the laboratory investigates the epigenomic regulation of cellular dysfunction in diabetes and metabolic diseases, identifies novel therapeutic targets in obesity and inflammation, and studies the fundamental mechanisms of transcription and chromatin biology.
- Signal-dependent epigenomic dynamics in diabetes. The epigenetic landscape of metabolic tissue, such as pancreatic islets, is shaped by metabolites and hormones. Dr. Wei's laboratory investigates the fundamental mechanisms of a new hormone-induced epigenetic switch that mediates pancreatic beta cell function in diabetes. The laboratory also explores 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. To identify novel factors involved in maintaining islet endocrine cell function and survival in stressed conditions, the laboratory of Dr. Wei combines CRISPR screening, stem cell-differentiated human islet-like organoids, and mouse genetic models to discover and explore the function of novel chromatin modulators. In addition, the team uses functional genomic tools to profile the epigenetic changes, including histone modification, chromatin accessibility and 3D long-range interactions, in endocrine and innate immune cells.
- 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 explores the crosstalk between residential immune cells and pancreatic endocrine cells in healthy and disease settings.
- Epigenetic modulation of glucocorticoid signaling in inflammation. Glucocorticoids are powerful anti-inflammatory hormones. The laboratory of Dr. Wei investigates the role of epigenetic co-factors, especially SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes, in modulating glucocorticoid receptor function in innate immune cells. The team explores the therapeutic potential of targeting epigenetic modulators to enhance glucocorticoid action in multiple inflammatory disease models.
- Developing next generation multi-omic platforms to interrogate tissue heterogeneity. The ability to profile multi-omic features at the resolution of a single cell revolutionizes our understanding of tissue heterogeneity. Dr. Wei's lab develops in-house multi-omic tools and computational platforms to characterize the diverse cellular population and the epigenetic potential in the pancreas at the single cell level.
Significance to patient care
In 2018, over 100 million people within the United States were either diabetic or prediabetic. By the year 2030, the obesity rate in the United States is expected to surpass 42%. Accordingly, obesity has been classified as a pandemic disease.
Both obesity and diabetes introduce a multitude of severely debilitating pathologies in patients, including blindness, kidney failure, stroke, cancer, heart disease, depression, neuropathy, loss of limbs, infertility and death. Because of these complications, millions of people rely daily on medications to regulate their fundamental metabolic processes.
- Mayo Clinic and Arizona State University (ASU) Alliance for Health Care Collaborative Research Seed Grant Program, 2021-2022
- Roubos Family Fund in Research, 2021-2022
- Beckman Coulter Life Sciences SPRI Grant Program for genomic research, 2021
- Mentored Research Scientist Development Award, NIDDK K01, 2019-2022
- Finalist, Initiator Award, Pathway to Stop Diabetes, American Diabetes Association, 2018
- Postdoctoral Training Fellowship, California Institute for Regenerative Medicine, 2012-2015
- Honorable mention, Ph.D. Achievement Award, University of Southern California, 2012