Positions

Professor
Medicine-Endocrinology
Baylor College of Medicine
Houston, TX, US
Professor
Molecular and Human Genetics
Baylor College of Medicine
Professor
Molecular and Cellular Biology
Baylor College of Medicine

Education

DSc from University Of Hong Kong
MBBS from University Of Hong Kong
Post-Doctoral Fellowship at Washington University

Professional Interests

  • Molecular pathogenesis and gene and cell therapy of diabetes
  • Role of hematopoietic cells in diabetic complications
  • Role of lipid droplet proteins in autophagy and ER stress

Professional Statement

Dr. Chan's laboratory is active in the following research areas: 1) Type 1 and type 2 diabetes and the metabolic syndrome, molecular biology and pathogenesis and 2) Somatic gene therapy and other molecular therapies for the treatment of diabetes and obesity.

Dr. Chan is interested in the molecular pathology of hyperglycemia and diabetic complications. Dr. Chan and his colleagues first described the appearance of insulin-producing cells in multiple extrapancreatic tissues in diabetes. The laboratory showed that the insulin-producing cells are derived from bone marrow cells that migrate from the bone marrow to multiple tissues, including the liver and adipose tissues. They may retain their bone marrow cell characteristics or they may fuse with the local cells in various tissues and organs. His laboratory further showed that the fusion of these abnormal bone marrow-derived cells with nerve cells is an important factor in diabetic neuropathy.

Dr. Chan developed a novel therapy for a type 1 diabetes model in mice. He showed that gene therapy-mediated delivery of a transcription factor, Neurog3 (together with an islet growth factor, betacellulin) to the liver of diabetic mice leads to the development of new islets in the liver. These islets produce insulin and other islet hormones, leading to complete correction of the diabetes. The gene therapy-induced islet neogenesis strategy that "cures" type 1 diabetes in mice is significant, not only for its potential as a new treatment, but also because it is the first time a single transcription factor has been shown to lead to the biogenesis of a complete organ (endocrine pancreas) in an adult animal. His laboratory showed that the newly formed β cells were derived from adult stem cells in the liver by a process consistent with transdetermination.

Glis3 is a krüppel-like zinc finger transcription factor that is expressed in essentially all cells in the body. The factor is expressed at high levels in pancreatic β cells. Genome wide association studies among adult populations have found a strong association of Glis3 polymorphisms in type 1 and type 2 diabetes. Intriguingly, mutations in Glis3 have been reported to cause a syndrome of neonatal diabetes. The Chan laboratory is interested in the developmental biology of the endocrine pancreas, particularly in the molecular pathology of the neonatal diabetes syndrome. They found that Glis3 regulates pancreatic islet growth and differentiation during fetal development in mice. Moreover, they showed that Glis3 is required for normal insulin gene expression; importantly, it is indispensable for normal β cell function and β cell mass maintenance in adult animals. His group is pursuing the molecular characterization of the action of Glis3 in pancreatic β cell biology and function.

In the area of metabolic syndrome and type 2 diabetes, the Chan laboratory is investigating the role of different fat cell proteins in carbohydrate and lipid homeostasis. They produced mutant mice, including those with inactivated perilipin and adipocyte differentiation related protein (ADRP), as well as the gene for multiple other lipid droplet proteins, to dissect the biochemical pathways that regulate lipolysis and energy metabolism in vivo. He is interested in the role of the lipid droplet proteins in the molecular pathogenesis of lipodystrophy and type 2 diabetes. They found that ADRP determines the lipid droplet protein composition of lipid droplets, including proteins that actively participate in the regulation of ER stress and autophagy. In other words, lipid droplet proteins control their own existence.

Selected Publications