- Baylor College of Medicine
- Houston, TX, US
- Molecular and Human Genetics
- Baylor College of Medicine
- Molecular and Cellular Biology
- Baylor College of Medicine
- DSc from University Of Hong Kong
- MBBS from University Of Hong Kong
- Post-Doctoral Fellowship at Washington University
- 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
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.
- Li R, Buras E, Lee J, Liu R, Liu V, Espiritu C, Ozer K, Thompson B, Nally L, Yuan G, Oka K, Chang B, Samson S, Yechoor V, Chan L. "Gene therapy with neurogenin3, betacellulin and SOCS1 reverses diabetes in NOD mice." Gene Ther. 2015 November;22:876-82. Pubmed PMID: 26172077
- Buras ED, Yang L, Saha P, Kim J, Mehta PC, Yang Y, Hilsenbeck S, Kojima H, Chen W, Smith CW, Chan L. "Proinsulin-producing, hyperglycemia-induced adipose tissue macrophages underlie insulin resistance in high fat-fed diabetic mice." FASEB J. 2015 August;29:3537-48. Pubmed PMID: 25953849
- Urabe H, Terashima T, Lin F, Kojima H, Chan L. "Bone marrow-derived TNF-a causes diabetic neuropathy." Diabetologia. 2015 February;58:402-410. Pubmed PMID: 25399355
- Poungvarin N, Chang B, Imamura M, Chen J, Moolsuwan K, Sae-Lee C, Li W, Chan L. "Genome-wide analysis of ChREBP binding sites on male mouse liver and white adipose chromatin.." Endocrinology. 2015 June;156:1982-94. Pubmed PMID: 25751637
- Oka K, Mullins C, Kushwaha R, Leen A, Chan L. "Gene therapy for rhesus monkeys heterozygous for LDL receptor deficiency by balloon-catheter hepatic delivery of helper-dependent adenoviral vector." Gene Ther. 2015 January;22(1):87-95. Pubmed PMID: 25231173
- Imamura M, Chang BH-J, Kohjima M, Li M, Hwang B, Taegtmeyer H, Harris RA, Chan L. "MondoA deficiency enhances sprint performance in mice." Biochem J. 2014 November;464:35-48. Pubmed PMID: 25145386
- Kojima H, Kim J, Chan L. "Emerging roles of hematopoietic cells in the pathobiology of diabetic complications." Trends Endo Metab. 2014 April;25:178-187. Pubmed PMID: 24507996
- Kohjima M, Tsai T, Tackett BC, Thevananther S, Li L, Chang BH-J, Chan L. "Delayed liver regeneration after partial hepatectomy in adipose differentiation-related protein-null mice." J Hepatol. 2013 December;59:1246-1254. Pubmed PMID: 23928401
- Chen W, Chang B, Wu X, Li L, Sleeman M, Chan L. "Inactivation of Plin4 downregulates Plin5 and reduces cardiac lipid accumulation in mice.." Am. J. Physiol. Endocrinol. Metab.. 2013 April;304(7):E770-9. Pubmed PMID: 23423172
- Chen W, Xie A, Chan L. "Mechanistic basis of immunotherapies for type 1 diabetes mellitus.." Transl Res. 2013 April;161(4):217-29. Pubmed PMID: 23348026
- Poungvarin N, Lee JK, Yechoor VK, Li MV, Assavapokee T, Suksaranjit P, Thepsongwajja JJ, Saha PK, Oka K, Chan L. "Carbohydrate response element-binding protein (ChREBP) plays a pivotal role in beta cell glucotoxicity.." Diabetologia. 2012;55(6):1783-96. Pubmed PMID: 22382520