The laboratory of Zong Wei, Ph.D., focuses on creating novel models to study diabetes and metabolism, and to identify therapeutic targets in metabolic 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. Rapid and chronic molecular responses are induced when pancreatic islets are exposed to adverse conditions. Although these responses at protein and transcriptional levels are well studied, 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 laboratory of Dr. Wei 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.
- 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 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.
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.
- Recipient, Mentored Research Scientist Development Award, NIDDK K01, 2019-2022
- Finalist, Initiator Award, Pathway to Stop Diabetes, American Diabetes Association, 2018
- Recipient, Postdoctoral Training Fellowship, California Institute for Regenerative Medicine, 2012-2015
- Honorable mention, Ph.D. Achievement Award, University of Southern California, 2012