Timothy J. Lyons, MD, FRCP Professor and Chief Chickasaw Chair in Diabetes Research Director, Harold Hamm Oklahoma Diabetes Center   Dr. Lyons' Research Group
Mailing Address: 920 Stanton L. Young Blvd., WP 1345 Oklahoma City, OK 73104-5020	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, 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 GCRC.

Education

Zhang, SX, Wang, JJ, Dashiti, A, Wilson, K, Zou, M-H, Szweda, L, Ma, J-x, and Lyons, TJ. Pigment Epithelium-derived Factor (PEDF) mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized-LDL. J Mol Endocrinol, June 27, 2008 [Epub ahead of print].

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

Lyons TJ, Li W, Wojciechowski B, Jenkins AJ.  Effects of D- and L-glucose, mannitol and aminoguanidine on retinal capillary cells.  Am J Pharmacol Toxicol.  in press, 2008.

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, Cunningham MW. Consequences of unlocking the cardiac myosin molecule in human myocarditis and cardiomyopathies.  J. Autoimmunity, in press, 2008

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

Brock JW, Jenkins AJ, Lyons TJ, Klein RL, Yim E, Lopes-Virella MF, Carter RE, Thorpe SR, Baynes JW.  Increased methionine sulfoxide content of apoA1 in type 1 diabetes.  J Lipid Res  E pub ahead of print, Jan 2008.

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. 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, 2007

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

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

Yu, Y., Thorpe, S.R., Waters, J.N., Sochaski, M.A., Jenkins, A.J., McGee, D., Orchard, T.J., Silvers, N., Peng, Y.G., McKnight, A.J., Baynes, J.W., Lyons, T.J., and The DCCT/EDIC Research Group.  AGE Accumulation and The Development Of Complications In Type I Diabetes.  Diabetologia, 49:2488-98, 2006.

Lopes-Virella, M.F., McHenry, M.B., Lipsitz, S., Yim, E., Wilson, P.F., Lackland,  D.T., Lyons, T.J., Jenkins, A.J., Virella, G.; The DCCT/EDIC Research Group. Immune Complexes Containing Modified Lipoproteins Are Related To The Progression Of Internal Carotid Intima-media Thickness In Patients With Type 1 Diabetes.  Atherosclerosis. 2006 Mar 9; [Epub ahead of print].

Lopes-Virella, M.F., Virella, G., Zheng, D., Atchley, D.H., Lyons, T.J., Klein, R.L., Lackland, D.T., Jenkins, A.J., McHenry, M.B., Garvey, W.T.   Concentrations Of Cholesterol and Apolipoprotein B In Circulating Immune Complexes Are Strong Predictors For Macro- and Microvascular Complications Of Diabetes.  Arteriosclerosis.  2006, in press.

Lyons, T.J., Jenkins, A.J., Zheng, D., Klein, R.L., Otvos, J.D., Yu, Y., Lackland, D.T., McGee, D., McHenry, M.B., Lopes-Virella, M.F., Garvey, W.T., 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, 23:955-66, 2006.

Alderson, N.L., Wang, Y., Blatnik, M., Frizzell, N., Walla, M.D., Lyons, T.J., Alt, N., Carson, J.A., Nagai, R., Thorpe, S.R., Baynes, J.W.  S-(2-succinyl) Cysteine: a Novel Chemical Modification of Tissue Proteins By A Krebs Cycle Intermediate. Arch Biochem Biophys 450:1-8, 2006

Soule, J.B., Hoda, R., Lyons, T.J. Pheochromocytoma Presenting As Presumed Metastatic Esophageal Carcinoma.  J South Carolina Medical Assoc 101:318-321, 2005.

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.

Reviews and Invited Papers

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

Books Chapters and Manuscripts

Colwell, J.A., Lyons, T.J., Klein, R.L., Lopes-Virella, M.F. New Concepts About The Pathogenesis Of Atherosclerosis In Diabetes Mellitus.  In: The Diabetic Foot, New edition. Levin, M.E., O'Neal, L.W., Bowker, J.H., eds.  Mosby, 2006 (in press).