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Molecular and Cellular Biology

Houston, Texas

Image 1: Ovulated mouse cumulus cell oocyte complex immunostained for matrix proteins hyaluronan and versican. By JoAnne Richards, Ph.D.; Image 2: By Yi LI, Ph.D.; Image 3: Mouse oocyte at meiosis I immunostained for tubulin (red) phosphop38MAPK (green) and DNA (blue). By JoAnne Richards, Ph.D.; Image 4: Expanded cumulus cell ooctye ocmplex immunostained for hyaluronan (red), TSG6 (green) and DAN (blue). By JoAnne Richards, Ph.D.; Image 5: Epithelial cells taken from a mouse mammary gland were cultured in a dish and transduced with a retrovirus expressing two genes. The green staining shows green fluorescent protein and the red staining shows progesterone receptor expression. The nucleus of each cell is stained blue. Photomicrograph taken at 200X magnification. By Sandra L. Grimm, Ph.D.; Image 6: Ovarian vasculature (red) is excluded from the granulosa cells (blue) within growing follicles (round structures); Image 7: Ovulated mouse cumulus cell oocyte complex immunostained for matrix proteins hyaluronan and versican. By JoAnne Richards, Ph.D.
Department of Molecular and Cellular Biology
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Lawrence Chan, M.B., B.S., D.Sc.

Lawrence Chan, M.B., B.S., D.Sc. photoProfessor
Departments of Molecular and Cellular Biology and Medicine

Education

M.B., B.S., D.Sc.: University of Hong Kong, Hong Kong, China
Postdoctoral training: Washington University, St. Louis

Research Interest

Diabetes, Gene Therapy, Insulin Resistance, Atherosclerosis, Lipoprotein Metabolism, Obesity
Dr. Chan's laboratory is active in the three following research areas:

  • Type 1 and type 2 diabetes and the metabolic syndrome
  • Lipoprotein metabolism and atherosclerosis
  • 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, NeuroD (together with an islet growth factor, betacelluln) 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.

In the area of metabolic syndrome and type 2 diabetes, the Chan laboratory is investigating the role of different fat cell-specific proteins in carbohydrate and lipid homeostasis. They produced mutant mice, including those with inactivated perilipin and adipocyte differentiation related protein (ADRP), to dissect the various biochemical pathways that regulate lipolysis and energy metabolism in vivo. In collaboration with investigators at MD Anderson Cancer Center, the Chan laboratory used a fat vasculature homing peptide to deliver a pro-apoptotic gene, leading to targeted ablation of adipose tissue and reversal of obesity and diabetes in mice. The laboratory is investigating the use of this "molecular liposuction" as a possible approach to the treatment of obesity in nonhuman primates.

The Chan laboratory has worked on the molecular genetics of lipoprotein metabolism for decades. In the last decade, it has been dissecting the role of cell cycle proteins and C-reactive protein on the cell biology and progression of atherosclerosis. More recently, they work on the role of lipid mediators as major determinants in atherosclerosis progression. In the area of gene therapy, with investigators in Molecular and Human Genetics, the Chan lab is a leader in the application of helper-dependent adenovirus for the treatment of genetic hyperlipidemia.

Contact Information

Baylor College of Medicine
One Baylor Plaza, Alkek N520.10
Houston, TX 77030

Phone: 713-798-4478
E-mail: lchan@bcm.edu

Selected Publications

  1. Paul A, Chang BH-J, Li L, Yechoor V and Chan L. (2008). Deficiency of adipose differentiation-related protein impairs foam cell formation and protects against atherosclerosis. Circ Res (in press).
  2. Merched AJ, Ko K, Gotlinger KH, Serhan CN and Chan L. (2008). Atherosclerosis: Evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators. FASEB J (in press).
  3. Matsumura K*, Chang BHJ*, Fujimiya M, Chen W, Kulkarni RN, Eguchi Y, Kimura H, Kojima H and Chan L. (2007). Aquaporin 7 is a ß cell protein and regulator of intra-islet glycerol content and glycerol kinase activity, ß cell mass, and insulin production and secretion. Mol Cell Biol (published online ahead of print 18 June, 2007). * These authors contributed equally to this study.
  4. Koeberl DD, Sun B, Bird A, Chen YT, Oka K and Chan L. (2007). Efficacy of helper-dependent adenovirus vector-mediated gene therapy in murine glycogen storage disease type Ia. Molecular Therapy 15:1253-1258.
  5. Fujimiya M, Kojima H, Ichinose M, Arai R, Kimura H, Kashiwagi A and Chan L. (2007). Fusion of proinsulin-producing bone marrow-derived cells with hepatocytes in diabetes. Proc Natl Acad Sci USA 104:4030-4035.
  6. Oka K, Belalcazar LM, Dieker C, Nour EA, Nuno-Gonzalez P, Paul A, Cormier S, Shin J-K, Finegold M and Chan L. (2007). Sustained phenotypic correction in a mouse model of hypoalphalipoproteinemia with a helper-dependent adenovirus vector. Gene Therapy 14:191-202.

    Chang BH-J, Li L, Paul A, Taniguchi S, Nannegari V, Heird WC and Chan L. (2006). Protection against fatty liver but normal adipogenesis in mice lacking adipose differentiation related protein (ADFP). Mol Cell Biol 26:1063-1076.
  7. Samson SL and Chan L. (2006). Gene therapy for diabetes: reinventing the islet. Trends Endocrinol Metab 17:92-100.
  8. Li MV, Chang B, Imamura M, Poungvarin N and Chan L. (2006). Glucose-dependent transcriptional regulation by an evolutionarily conserved glucose-sensing module. Diabetes 55:1179-1189.
  9. Terashima T, Kojima H, Fujimiya M, Matsumura K, Oi J, Hara M, Kashiwagi A, Kimura H, Yasuda H and Chan L. (2005). The fusion of bone marrow-derived proinsulin-expressing cells with nerve cells underlies diabetic neuropathy. Proc Natl Acad Sci USA 102:12525-12530.

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