Lawrence C. B. Chan, M.D.
Betty Rutherford Chair for Diabetes Research
Professor of Medicine and Molecular & Cellular Biology
Chief, Division of Diabetes, Endocrinology & Metabolism
Director, Diabetes & Endocrinology Research Center
One Baylor Plaza (MS: BCM185)
Houston, TX 77030
Dr. Lawrence Chan is the Betty Rutherford Chair for Diabetes Research and and the director of the NIH-funded Diabetes & Endocrinology Research Center at Baylor College of Medicine. He is also the director of the Molecular Medicine Scholars Program and a professor in the departments of Medicine and Molecular and Cellular Biology.
He is recognized as a preeminent investigator in the development of novel therapies in Diabetes, and an authority in the genetics of atherosclerosis and lipid disorders. Dr. Chan was the recipient of a MERIT Award from the National Institutes of Health and is principal investigator of multiple NIH grants. He has received numerous national and international honors and awards from organizations including the American Diabetes Association, the Endocrine Society, the American Heart Assocition and the Juvenile Diabetes Research Association. He is also an elected member of the American Society for Clinical Investigation and the Association of American Physicians.
- M.B., B.S.; D.Sc.: University of Hong Kong
- Postdoctoral: Washington University, St. Louis
- Dr. Chan's laboratory is active in the following research areas: (1) type 1 and type 2 diabetes and the metabolic syndrome, (2) lipoprotein metabolism and atherosclerosis, and (3) 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 hyperglycemic states, resulting from type 1 and type 2 diabetes or simply glucose injection-induced hyperglycemia. The laboratory showed that the insulin-producing cells are derived from bone marrow cells, which are induced to express multiple islet hormones in response to elevated blood glucose. These cells 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, possibly mediating some of the chronic diabetic complications. His laboratory is investigating the possible role of these peripheral insulin-producing cells in the modulation of autoimmune (type 1) diabetes, and as a causative factor of different chronic diabetic complications.
- 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. For example, they found that perilipin-null mice are lean and resistant to diet-induced and genetic obesity, and that the absence of perilipin activates a number of biochemical pathways that enable these animals to efficiently burn the extra fat and stay lean.
- The Chan laboratory has been active in the lipoprotein/atherosclerosis area for over twenty-five years. He and his coworkers first cloned the vertebrate apolipoprotein genes, developed the now widely accepted apolipoprotein multigene family concept, and discovered apolipoprotein B mRNA editing. They cloned the different vascular lipase genes and were among the first to describe the molecular genetics and the specific mutations in families with type 1 hyperlipoproteinemia. They recently showed that mice with inactivate endothelial lipase have elevated high density lipoprotein (HDL), defining an important role for this newly described vascular lipase. They also found an association between a single nucleotide polymorphism in the endothelial lipase gene and plasma HDL cholesterol concentration in humans. Using various mouse mutants, the Chan laboratory dissected the molecular pathology of atherosclerosis development. It determined the role of different cell cycle-related molecules, such as p53 and p21, in atherosclerosis, providing mechanistic insight into the diverse actions of these proteins on apoptosis, cellular proliferation, and inflammation, in the context of atherosclerosis. His laboratory also produced the initial evidence that C-reactive protein (CRP) is a pro-atherogenic molecule in mice in vivo, indicting that CRP is not simply a clinical marker, but an active player, in atherosclerosis.
- In the area of molecular therapy, Dr. Chan's laboratory has been developing gene therapy regimens that not only inhibit atherosclerosis development, but also remodel atheromatous plaques, changing them from vulnerable to stable-looking lesions. In collaboration with the Department of Molecular and Human Genetics, Dr. Chan has been in the forefront of adenviral vector application and development. Use of the helper-dependent adenovirus developed by this collaboration leads to stable long-term transgene expression and life-time reversal of genetic hyperlipidemia in mice.
- Metabolic syndrome is a major cause of type 2 diabetes, and obesity is a dominant pathological factor in the process. 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.
Terashima T, Kojima H and Chan L (2012)Bone marrow expression of poly(ADP-ribose) polymerase underlies diabetic neuropathy via hematopoietic-neuronal cell fusion. FASEB J 26: 295-308, 2012. PMID: 21978940PMCID: PMC3250244
Poungvarin N, Lee JK, Yechoor VJ, Li MV, Assavapokee T, Suksaranjit P, Chen W, Chang B, Saha P, Hartig SM, Li L, Reddy VT, Yang Y, Yechoor Y and Chan L (2012) Berardinelli-Seip congenital lipodystrophy-2 (BSCL2)/Seipin is a cell autonomous regulator of lipolysis essential for adipocyte differentiation. Mol Cell Biology (Epub ahead of print).PMID:22269949
Li, R, Paul A, Ko KW, Sheldon M, Rich Be, Terashima T, Dieker C, Cormier S, Li L, Nour EA, Chan L and Oka K. (2012) Interleukin-7 induces recruitment of monocytes/macrophages to endothelium. Eur Heart jJ. Jul 30. PMID: 21804111
Chan L, Terashima T, Hiroshi U, Lin F and Kojima H (2011) Pathogenesis of diabetic neuropathy: bad to the bone. Ann N Y Acad Sci. 2011 Dec;1240:70-6. PMID: 22172042
Samson SL, Sathyanarayana P, Jogi M, Gonzalez EV, Gutierrez A, Krishnamurthy R, Muthupillai R, Chan L, Bajaj M (2011) Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial. Diabetologia. 2011 Dec;54(12):3093-100. PMID: 21956711
Tschöp MH, Speakman JR, Arch JR, Auwerx J, Brüning JC, Chan L, Eckel RH, Farese RV Jr, Galgani JE, Hambly C, Herman MA, Horvath TL, Kahn BB, Kozma SC, Maratos-Flier E, Müller TD, Münzberg H, Pfluger PT, Plum L, Reitman ML, Rahmouni K, Shulman GI, Thomas G, Kahn CR, and Ravussin E (2011) A guide to analysis of mouse energy metabolism. Nat Methods. 2011 Dec 28;9(1):57-63. PMID: 2205519
Barnhart KF, Christianson DR, Hanley PW, Driessen WH, Bernacky BJ, Baze WB, Wen S, Tian M, Ma J, Kolonin MG, Saha PK, Do KA, Hulvat JF, Gelovani JG, Chan L, Arap W, Pasqualini R (2011) A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci Transl Med. 2011 Nov 9;3(108):108ra112. PMID: 22072637
Yamakawa I, Kojima H, Terashima T,Katag M,Oi, J,Hiroshi, U, Sanada M,Kawai H, Chan L,Yasuda H, Maegawa H and Kimura H (2011) Inactivation of TNF-αameliorates diabetic neuropathy in mice. Am J Physiol Endocrinol Metab 301(5): E844-E852. PMID: 21810933
Yang Y, Chang BH, Yechoor V, Chen W, Li L, Tsai MJ, Chan L (2011) The Krüppel-like zinc finger protein GLIS3 transactivates neurogenin 3 for proper fetal pancreatic islet differentiation in mice. Diabetologia. Oct;54(10):2595-605. Epub 2011 Jul 23. PMID: 21786021
Li Y, Kojima H, Fujino K, Matsumura K, Katagi M, Urabe H, Chan L, Eguchi Y, Zhao L, Kimura H (2011) Homing of the bone marrow-derived interstitial cells of Cajal is decreased in diabetic mouse intestine. J Gastroenterol Hepatol. Jun;26(6):1072-8. PMID: 21265880
Terashima T, Kojima H, Chan L (2011) Bone marrow expression of poly(ADP-ribose) polymerase underlies diabetic neuropathy via hematopoietic-neuronal cell fusion. FASEB J. 2012 Jan;26(1):295-308. PMID: 21978940
Cheng N-H, Zhang W, Chen W-Q Jin J, Cui X, Butte NF, Chan L, Hirschi KD (2011) A mammalian monothiol glutaredoxin, Grx3, is critical for cell-cycle progression during embryogenesis. FEBS Journal Jul 278(14):2525-39. PMID: 21575136
Merched A, Serhan CN, Chan L (2011) Nutrigenetic disruption of inflammation-resolution homeostasis and atherosclerosis. Journal of Nutrigenetics and Nutrigenomics 4(1):12-24. PMID: 21474962
Shah B and Chan L (2011) Primary Aldosteronism. In Conn’s Current Therapy. Bope ET, Kellerman R, Rakel RE, editors. Section 8 Metabolic Disorders. PP 666-673.
Ozer K and Chan L (2011) Dyslipoproteinemias. In Conn’s Current Therapy. Bope ET, Kellerman R, Rakel RE, editors. Section 8 Metabolic Disorders. PP 618-622
Chopra AR, Kommagani R, Saha P, Louet J-F, Salazar C, Song J, Jeong J, Finegold M, Viollet B, DeMayo F, Chan L, Moore DD, O'Malley BW (2011) Cellular Energy Depletion Resets Whole-Body Energy by Promoting Coactivator-Mediated Dietary Fuel Absorption. Cell Metab 13: 35-43. PMCID:PMC3072049
Saha PK, Reddy VT, Konopleva M, Andreeff M, Chan L (2010) The triterpernoid CDDO-Me has potent antidiabetic effects in diet-induced diabetic mice and Leprdb/db mice. J Biol Chem 285: 40581-40592. PMCID:PMC3003357
Sharma R, Buras ED, Terashima T, Serrano F, Massaad C, Hu L, Bitner B, Inoue T, Chan L, Pautler RG (2010) Hyperglycemia induces oxidative stress and impairs axonal transport rates in mice. PLoS ONE 5(10): e13463. PMCID:PMC2956689
Ozer K, Chan L (2010). Gene Therapy for Diabetes. In Treatment Strategies Diabetes. Pages 106-110. Edited by The Cambridge Research Centre and published in line with The EASD Congress 2010, Stockholm, Sweden 20-24 Sep 2010
Chen W, Chang B, Li L, Chan L (2010) Patatin-like phophplipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease. Hepatology 52: 1134-1142. PMID: 20648554 PMCID:PMC2932863
Lovren F, Pan Y, Quan A, Szmitko PE, Singh KK, Shukla PC, Gupta M, Chan L, Al-Omran M, Teoh H, Verma S (2010) Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages. Am J Physiol Heart Circ Physiol. 299: H656-H663. PMCID:PMC2944489