Timothy J. Lyons, MD, FRCP Professor and Chief, Section of Endocrinology & Diabetes Chickasaw Chair in Diabetes Director, Harold Hamm Oklahoma Diabetes Center   Dr. Lyons' Research Group
Mailing Address: 1000 N. Lincoln Blvd., HHDC 2900 Oklahoma City, OK 73104-3252	Telephone: (405) 271-3613 Fax: (405) 271-7522
Email: timothy-lyons@ouhsc.edu

Research Interests

Personal:
The overall aim of the work in my laboratory is to gain a better understanding of the biochemical basis and mechanisms of the complications of diabetes, including diabetic eye disease (retinopathy), diabetic kidney disease (nephropathy), and the acceleration of atherosclerosis in diabetes.  In combined clinical/basic science projects, we use samples obtained from patients with diabetes studied locally, and through collaboration with other centers and with the Diabetes Control and Complications Trial and the VA Diabetes Trial.  We also study the disease mechanisms for the four-fold increase in the prevalence of pre-eclampsia, a complication of pregnancy, in women with diabetes, and have collected a unique, prospective sample collection from 175 pregnant women (145 with Type 1 diabetes and 30 non-diabetic controls).  These samples are studied to assess the roles of dyslipidemia, oxidative stress, inflammation and endothelial dysfunction in the complications of diabetes.  Our work focuses on the consequences of reactions between glucose (levels of which are elevated in diabetes) and other body constituents, especially plasma lipoproteins (which transport cholesterol and other fats in the circulation) and connective tissue proteins.  The reactions between glucose and proteins, termed "glycation", may lead to altered chemical properties in the affected molecules, which in turn may contribute to disease.  Similarly, increased oxidative stress in diabetes may cause irreversible damage to variety of macromolecules, and the two processes combined are termed "glycoxidation."  In cell culture work, we study the consequences of these stresses, particularly with regard to signaling, gene expression, oxidative stress and apoptosis/proliferation.  A final, important goal is the provision of well-characterized samples from diabetic subjects to basic science researcher groups across campus in order to enable them to apply unique skills to the investigation of diabetic vascular disease.             

Administrative:
The promotion of clinical research and the integration of effort between clinical and basic science researchers. These goals are pursued both in the Section of Endocrinology and Diabetes, and through the Harold Hamm Oklahoma Diabetes Center.

Education

Azar M, Basu A, Jenkins AJ, Nankervis AJ, Hanssen KF, Scholz H, Henriksen T, Garg SK, Hammad SM, Scardo JC, Aston CE, Lyons TJ.  Serum carotenoids and fat-soluble vitamins in women with Type 1 diabetes and pre-eclampsia: a longitudinal study.  Diabetes Care.  In press, 2011.

Basu A, Betts NM, Ortiz J, Simmons B, Wu M-Y, Lyons TJ. Low-calorie Cranberry Juice Decreases Lipid Oxidation and Increases Plasma Antioxidant Capacity in Women with Metabolic Syndrome. Nutrition Res 2011 (in press)

Basu A, Sanchez K, Leyva MJ, Wu M, Aston CE, Lyons TJ. Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome. J. Am Coll. Nutr., 29 :31-40, 2010.

Dong Y, Zhang M, Wang S, Zhao Z, Chao L, Wu M, Choi HC, Lyons TJ, Zou MH.  Activation of AMP-activated Protein Kinase inhibits oxidized Low Density Lipoprotein-triggered Endoplasmic Reticulum (ER) stress and endothelium dysfunction in vivo.  Diabetes, 59:1386-96, 2010.

Basu A, Sanchez K, Leyva MJ, Wu M, Aston CE, Lyons TJ. Green Tea minimally affects  biomarkers of inflammation in obese subjects with metabolic syndrome.  Nutrition.  Epub ahead of print, 2010.

Klein RL, Carter RE, Jenkins AJ, Lyons TJ,  Baker NL, Gilbert GE, Virella G, Lopes-Virella MF and the DCCT/EDIC Research Group.  LDL-Containing Immune Complexes in the DCCT/EDIC Cohort: Associations with Lipoprotein Subclasses.  J. Diab. Complications.  Epub ahead of print, 2010.

Basu A, Du M, Leyva MJ, Sanchez K, Betts NM, Wu M-Y, Aston CE, Lyons TJ. Blueberries improve cardiovascular risk factors in obese subjects with metabolic syndrome.  J. Nutrition  140:1582-7, 2010.

Basu A, Fu DX, Wilkinson M, Simmons B, Wu M, Betts NM, Du M, Lyons TJ.  Strawberries decrease atherosclerotic markers in subjects with metabolic syndrome.  Nutr Res. 30:462-9, 2010.

Hoofnagle AN, Wu M, Gosmanova AK, Becker JO, Wijsman EM, Brunzell JD, Kahn SE, Knopp RH, Lyons TJ, Heinecke JW.  Low Clusterin levels in HDL associated with insulin resistance, obesity, and dyslipoproteinemia.  Arterioscler Thromb Vasc Biol  30:2528-34, 2010.

Zhou T, Zhou KK, Lee K, Gao G, Lyons TJ, Kowluru R, Ma JX.   The role of lipid peroxidation products and oxidative stress in activation of the canonical wingless-type MMTV integration site (WNT) pathway in a rat model of diabetic retinopathy.  Diabetologia 2010, (epub ahead of print).  PMID:  20978740.

Jenkins AJ, McBride JD, Januszewski AS, Karschimkus CS, Zhang B, O’Neal DN, Nelson CL, Chung JS, Harper CA, Lyons TJ, Ma J-X. Increased Serum Kallistatin Levels in Patients with Type 1 Diabetes and its Vascular Complications.  J. Angiogenesis Res. 2:19, 2010.

Letassy N, Dennis V, Lyons TJ, Harrison D, Burton M, Kirkpatrick A. (2010).  Know your diabetes risk project:  pharmacy students educating adults about diabetes risk in a community pharmacy setting.  J Am Pharm Soc 50:188-194.

Basu A, Sanchez K, Leyva MJ, Wu M, Aston CE, Lyons TJ. (2010).  Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome. J. Am Coll. Nutr.  In press.

Dong Y, Zhang M, Wang S, Zhao Z, Chao L, Wu M, Choi HC, Lyons TJ, Zou MH.  (2010).  Activation of AMP-activated Protein Kinase inhibits oxidized Low Density Lipoprotein-triggered Endoplasmic Reticulum (ER) stress and endothelium dysfunction in vivo.  Diabetes, 59:1386-96.

Yu Y, Jenkins AJ, Nankervis AJ, Hanssen K, Scholz H, Henriksen T, Lorentzen B, Garg SK, Menard MK, Hammad SM, Scardo JC, Stanley JR, Dashti A, May K, Lu K, Aston CE, Zhang SX, Ma J-X, and Lyons TJ. (2009). Antiangiogenic factors and the prediction of pre-eclampsia in Type 1 diabetes.  Diabetologia 52:160-8.

Valaydon ZS, Lee P, Dale GL, Januszewski AS, Rowley KG, Nandurkar H, Best JD, Lyons TJ, and Jenkins AJ. (2009). Coated platelets in chronic hemodialysis patients.  Nephrology 14:148-54.

Diffley M, Wu M, Sohn M, Song W, Hammad SM, and Lyons TJ. (2009).  Activation of MAPK by Native and Modified LDL in Retinal Capillary Pericytes.  Mol Vision 15:135-45 PMCID: PMC2628314.

Kielczewski JL, Jarajapu Y, McFarland EL, Cai J, Afzal A, Calzi SL, Chang KH, Lydic T, Shaw LC, Busik J, Hughes J, Cardounel AJ, Wilson K, Lyons TJ, Boulton ME, Mames RN, Chan-Ling T, and Grant MB. (2009).  Insulin-like growth factor binding protein-3 (IGFBP-3) mediates recruitment and differentiation of bone marrow derived cells during vascular repair by enhancing nitric oxide generation.  Circ Res 105:897-905.

Chen Y, Hu Y, Zhou T, Zhou KK, Mott R, Wu MY, Boulton ME, Lyons TJ, Gao G, and Ma JX. (2009). Activation of the Wnt Pathway, a Pathogenic Mechanism for Diabetic Retinopathy in Humans and Animal Models.  Am J Path 175:2676-85.

Basu A, Wilkinson M, Penugonda K, Simmons B, Betts NM, and Lyons TJ. (2009).  Freeze-dried strawberry powder improves lipid profile and lipid peroxidation in women with metabolic syndrome: baseline and post intervention effects.  Nutr J: Published online 2009 September 28. doi: 10.1186/1475-2891-8-43.  PMCID: PMC2761419

Brock JW, Jenkins AJ, Lyons TJ, Klein RL, Yim E, Lopes-Virella MF, Carter RE, Thorpe SR, and Baynes JW. (2008).  Increased methionine sulfoxide content of apoA1 in type 1 diabetes.  J Lipid Res 49:847-55.

Jenkins AJ, Lyons TJ, Rothen M, Moller K, Klein RL, Zheng D, McGee D, Thorpe SR, Garvey WT, and The DCCT/EDIC Research Group.  (2008). Cross-sectional Associations of C-Reactive Protein with Vascular Risk Factors and Vascular Complications in the DCCT/EDIC Cohort.  Journal Diabetes & its Complications. 22:153-163.

Wu M, Chen Y, Wilson K, Chirindel A, Ihnat MA, Yu Y, Boulton ME, Szweda LI, Ma J-X, and Lyons TJ. (2008). Intra-retinal leakage and oxidation of LDL in diabetic retinopathy.  Invest Ophthalmol Vis Sci 49:2679-85.

Mascaro-Blanco A, Alvarez K, Yu X, Lindenfeld J, Olansky L, Lyons TJ, Duvall D, Heuser JS, Gosmanova AK, Rubenstein CJ, Cooper LT, Kem DC, and Cunningham MW. (2008). Consequences of unlocking the cardiac myosin molecule in human myocarditis and cardiomyopathies.  Autoimmunity 41:442-453.

Jenkins AJ, Gosmanova AK, Lyons TJ, May KD, Dashti A, Baker MZ, Olansky L, Aston CE, and Dale GL. (2008).  Coated-Platelet Levels in Patients with Type 1 and with Type 2 Diabetes Mellitus.  Diab Res Clin Practice 81:e8-e10.

Jenkins A, Zhang SX, Gosmanova A, Aston C, Dashti A, Baker MZ, Lyons TJ, and Ma JX. (2008). Increased serum pigment  epithelium-derived factor in Type 2 diabetes patients.  Diabetes Res Clin Pract. 82:e5-7.  PMCID: PMC2597065.

Zhang SX, Wang JJ, Dashti A, Wilson K, Zou MH, Szweda L, Ma JX, and Lyons TJ. (2008). Pigment Epithelium-derived Factor (PEDF) mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized-LDL. J. Molecular Endocrinology 41:135-143. PMCID: PMC2714421.

Lopes-Virella MF, Carter RE, Gilbert GE, Klein RL, Jaffa M, Jenkins AJ, Lyons TJ, Garvey WT, Virella G and the DCCT/EDIC Study Group. (2008).  Circulating Levels of Biomarkers of Inflammation and Endothelial Dysfunction in the DCCT/EDIC Cohort: Relationship with Nephropathy and Macrovascular Complications.  Diabetes Care 31:2006-12. PMCID: PMC2551645.

Dong Y, Wu Y, Wu M, Wang S, Zhang J, Xie Z, Xu J, Song P, Wilson K, Zhao Z, Lyons TJ, and Zou MH. (2008).  Activation of the Calcium-Dependent μ-Calpain by Oxidized and Glycated LDL Triggers the Degradation of Endothelial Nitric Oxide Synthase.  J. Cell. Mol. Med.  Epub ahead of print.

Lopes-Virella MF, McHenry MB, Lipsitz S, Yim E, Wilson PF, Lackland DT, Lyons TJ, Jenkins AJ, Virella G, and the DCCT/EDIC Research Group. (2007). Immune complexes containing modified lipoproteins are related to the progression of internal carotid intima-media thickness in patients with type 1 diabetes. Atherosclerosis 190:359-369.

Firdaus M, and Lyons TJ. (2007).  Preventing diabetes and cardiovascular disease in older adults: controlling metabolic syndrome through lifestyle interventions.  Geriatrics and Aging 10:561-568.

Barth JL, Yu Y, Song W, Huang Y, Lu K, Argraves WS, and Lyons TJ. (2007). Oxidation/Glycation of LDL Blocks its Regulation of TIMP-3 Expression in Human Retinal Capillary Pericytes.  Diabetologia 50:2200-2208.

Jenkins AJ, Zhang SX, Rowley KG, Karschimkus CS, Nelson CL, Chung JS, O'Neal DN,  Januszewski AS, Croft KD, Mori TA, Dragicevic G, Harper CA, Best JD, Lyons TJ, and Ma JX. (2007). Increased Serum Pigment Epithelium Derived Factor is Associated with Microvascular Complications, Vascular Stiffness, and Inflammation in Type 1 Diabetes.  Diabetic Medicine 24:1345-51.

Lopes-Virella MF, McHenry MB, Lipsitz S, Yim E, Wilson PF, Lackland  DT, Lyons TJ, Jenkins AJ, Virella G; The DCCT/EDIC Research Group. (2007). Immune Complexes Containing Modified Lipoproteins Are Related To The Progression Of Internal Carotid Intima-media Thickness In Patients With Type 1 Diabetes.  Atherosclerosis 190:359-369.

Yu Y, Thorpe SR, Waters JN, Sochaski MA, Jenkins AJ, McGee D, Orchard TJ, Silvers N, Peng YG, McKnight AJ, Baynes JW, Lyons TJ, and The DCCT/EDIC Research Group. (2006). AGE Accumulation and The Development Of Complications In Type I Diabetes.  Diabetologia, 49:2488-98.

Lyons TJ, Jenkins AJ, Zheng D, Klein RL, Otvos JD, Yu Y, Lackland DT, McGee D, McHenry MB, Lopes-Virella MF, Garvey WT, and The DCCT/EDIC Research Group. (2006). Nuclear Magnetic Resonance-determined Lipoprotein Subclass Profile In The DCCT/EDIC Cohort: Associations With Carotid Intima-medial Thickness.  Diabetic Medicine, 23:955-66.

Alderson NL, Wang Y, Blatnik M, Frizzell N, Walla MD, Lyons TJ, Alt N, Carson JA, Nagai R, Thorpe SR, and Baynes JW. (2006). S-(2-succinyl) Cysteine: a Novel Chemical Modification of Tissue Proteins By A Krebs Cycle Intermediate. Arch Biochem Biophys 450:1-8.

Soule JB, Hoda R, and Lyons TJ. (2005). Pheochromocytoma Presenting As Presumed Metastatic Esophageal Carcinoma.  J South Carolina Medical Assoc 101:318-321.

Klein RL, Hunter SJ, Le N-A, Jenkins AJ, Zheng D, Semler A, Page G, Brown WV, Lyons TJ, Garvey WT, DCCT/EDIC Research Group. (2005). Apolipoprotein C-III Protein Concentrations and NMR profile in Type 1 Diabetes. J Diabetes and its Complications 19:18-25.

Schaumberg DA, Glynn RJ, Jenkins AJ, Lyons TJ, Rifai N, Manson JE, Ridker PM, and Nathan DM. (2005). Effect of intensive glycemic control on levels of markers of inflammation in the diabetes control and complications trial. Circulation 111:2446-53.

Song W, Lu K, Yu Y, Huang Y, Barth J, Argraves S, and Lyons TJ. (2005). Effect of Native LDL and Modified LDL on mRNA Expression of Genes in Human Retinal Pericytes. Invest Ophthalmol Vis Sci 46:2974-82.

Song W, Barth JL, Lu K, Yu Y, Huang Y, Gittinger CK, Argraves WS, and Lyons TJ. (2005). Effects of modified low-density lipoproteins on human retinal pericyte survival. Ann N Y Acad Sci 1043:390-5.

Klein RL, Semler AJ, Baynes JW, Thorpe SR, Lyons TJ, and Jenkins AJ. (2005). Glycation Does Not Alter LDL-Induced Secretion of Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 from Human Aortic Endothelial Cells. Ann N Y Acad Sci 1043:379-89.

Reviews and Invited Papers

Basu A, Rhone M, and Lyons TJ. (2010). Berries: Emerging Impact on Cardiovascular Health. Nutrition Reviews  68:168-177, 2010.

Azar M, and Lyons TJ. (2010).  Diabetes, insulin treatment, and cancer risk: what is the evidence?  F1000 Medicine Reports 2:4 (doi:10.3410/M2-4)

Wu M, and Lyons TJ. (2009). Treatment approach to diabetes and dyslipidemia.  Hormone Research. 2009, in press.

Firdaus M, and Lyons TJ. (2007).  Preventing diabetes and cardiovascular disease in older adults: controlling metabolic syndrome through lifestyle interventions.  Geriatrics and Aging 10:561-568.

Yu Y, and Lyons TJ.  (2005). A Lethal Tetrad In Diabetes: Hyperglycemia, Dyslipidemia, Oxidative Stress, and Endothelial Dysfunction.  Am J Med Sci 330:227-232.

Books Chapters and Manuscripts

Colwell JA, Lyons TJ, Klein RL, and Lopes-Virella MF. (2006). New Concepts About The Pathogenesis Of Atherosclerosis In Diabetes Mellitus.  In: The Diabetic Foot, New edition. Levin ME, O'Neal LW, Bowker JH, eds.  Mosby, 2006 (in press).