Professor and Chief
W.K. Warren Chair in Diabetes Research

Program Director, General Clinical Research Center
Medical Director, Oklahoma Diabetes Center

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, particularly 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, both studied locally, and through collaboration with two large national cohorts, 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 vascular complications of diabetes. The work also addresses 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". Our work utilizes culture of cells affected by diabetes, focusing mainly on retinal capillary pericytes. We study the consequences of these stresses, particularly with regard to signaling, gene expression, and apoptosis/proliferation. A final, important goal is the provision of well-characterized samples from diabetic subjects to basic science researchers 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 OUHSC General Clincal Research Center.

Education:

1977 MB BCh BAO The Queen's University of Belfast

1980 MRCP (UK) Royal Colleges of Physicians

1985 MD (by Thesis) The Queen's University of Belfast

Recent Publications:

Lyons TJ. Glycation, carbonyl stress, EAGLEs, and the vascular complications of diabetes. Seminars in Vascular Medicine 2:175-189, 2002. Editor: Michiels JJ. Thieme, New York.

Lyons TJ, Jenkins A, Klein R, Otvos J, Zheng D, Lackland D, McGee D, Garvey WT, & The DCCT/EDIC Research Group. NMR-determined lipoprotein profile in Type I diabetes: effects of gender and glycemia. Diab Care 26:810-8, 2003

Lyons TJ, Jenkins A, Zheng D, Otvos J, Klein R, Lackland D, McGee D, Garvey WT, & DCCT/EDIC Research Group. Serum lipoproteins in the DCCT cohort: associations with diabetic nephropathy. Kid Internat, 64:817-828, 2003.

Hammad SM, Powell-Braxton L, Eldridge L, Won W, Otvos JD, Lyons TJ. Lipoprotein Subclass Profiles of hyperlipidemic Diabetic Mice Measured by Nuclear Magnetic Resonance Spectroscopy. Metabolism, 52:916-21, 2003.

Hammad SM, Hazen-Martin DJ, Sohn M, Eldridge L, Powell-Braxton L, Won W, Lyons TJ. Nephropathy in a hyper-lipidemic mouse model with streptozotocin-induced diabetes. Kidney & Blood Pressure Research, 26:351-61, 2003

Lyons TJ, Jenkins A, Zheng D, Otvos J, Klein R, Lackland D, McGee D, Garvey WT, & DCCT/EDIC Group. Serum lipoproteins in DCCT/EDIC: associations with diab retinopathy. Invest Ophthalmol Vis Sci; 45: 910-918, 2004.

Jenkins AJ, Thorpe SR, Alderson NL, Hermayer KL, Lyons TJ, King LP, Chassereau C, Klein RL. In vivo glycated LDL is not more susceptible to oxidation than non-glycated LDL in type 1 diabetes. Metabolism; 53:969-76 2004

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. Apolipoprotein C-III Protein Concentrations and Gene Polymorphisms in Type 1 Diabetes: Associations with Microvascular Disease Complications in the DCCT/EDICT Cohort. Metabolism 53:1296-1304, 2004

Jenkins AJ, Best JD, Klein RL, Lyons TJ. Lipoproteins, Glycoxidation, and Diabetic Angiopathy. Invited Review. Diabetes Metabolism Research and Reviews 20:349-368, 2004.

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. Apolipoprotein C-III Protein Concentrations and NMR profile in Type 1 Diabetes.J Diabetes and its Complications 19:18-25, 2005.

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

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

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

Klein RL, Semler AJ, Baynes JW, Thorpe SR, Lyons TJ, Jenkins AJ. 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, 2005.

Yu Y, Lyons TJ. A Lethal Tetrad in Diabetes: Hyperglycemia, Dyslipidemia, Oxidative Stress, and Endothelial Dysfunction. Am J Med Sci In press, 2005

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. Nuclear magnetic resonance-determined lipoprotein subclass profile in the DCCT/EDIC cohort: associations with carotid intima-medial thickness. Diabetic Medicine In press, 2005.