Vincent M. Monnier, M.D. Professor Mailing Address: 2103 Cornell Rd. WRB 5127 Cleveland, OH 44106-7288 phone: (216) 368-6613 fax: (216) 368-0494 email: Vincent.Monnier@Case.edu

Laboratory

Biography
Vincent Monnier obtained his medical degree and diploma in Chemistry from the University of Basel, Switzerland. From 1977-82, he did postdoctoral research on the advanced Maillard reaction in vivo with Anthony Cerami, Ph.D. at Rockefeller University (New York, NY). In 1982, he joined the Institute of Pathology where he did his residency in Clinical Pathology (1982-85). His research focuses on the structure and significance of protein modification by advanced Maillard reaction and oxidation products in aging and age-related diseases, including diabetes, cataract and end stage renal disease. Awards: 1990, Paul E. Lacy Award, 1996 Nathan Shock Award (National Institute of Aging) for his work on the structure of protein crosslinks from senescent human collagen.

Research
The focus of our laboratory is to elucidate the molecular mechanisms by which the aging process leads to impairment of protein function. In particular we are interested in the structure and biological role of protein modifications by reducing sugars (Maillard reaction) and reactive oxygen species. These reactions are dramatically accelerated in diabetes, in patients with end stage renal disease and atherosclerosis, and during the formation of cataracts. The structure of the modified proteins is analyzed by mass-spectrometry, whereby particular emphasis is being placed on the structure of collagen crosslinks which increase with age and are responsible for the progressive stiffening of aging vessels. Using an approach based on molecular biology, we are seeking to find novel microbial enzymes that can degrade glycated proteins and specifically regenerate the native protein. We are currently developing transgenic animal models of accelerated aging based on overexpression of the human vitamin C transporter into the lens, and the knocking out of glutathione synthesis, i.e. a key defense against aging.

The International Maillard Reaction Society

Publications
Satake M. Dmochowska, B.Nishikawa Y, Madaj J, Xue J, Guo Z.Reddy VD, Rinaldi PL, Monnier VM. Vitamin C metabolomic mapping in the lens with 6-deoxy-6-fluoro-ascorbic acid and high resolution 19F-NMR spectroscopy. Invest. Ophthalmol Vis. Sci. 44: 2047-2058, 2003.

Sell D.R., Monnier V.M. Conversion of arginine to ornithine by advanced glycation in aging human collagen and lens crystallins. J. Biol. Chem. 259, 54173-184, 2004.

Mustata GT, Rosca M, Biemel KM, Weiss MF, Monnier VM. Paradoxical Effects of Green Tea (Camellia Sinensis) and Antioxidant Vitamins in Experimental Diabetes : Improved Retinopathy and Renal Mitochondrial Defects but Deterioration of Collagen Matrix Glycoxidation and Crosslinking. Diabetes. 54:517-26, 2005.

Sell, D.R., Biemel K, Reihl O, Lederer M.O., Monnier V.M. Glucospane is a major crosslink of the aging extracellular matrix. J. Biol. Chem. 280:12310-5, 2005.

Genuth S, Bautista O, Cleary P, Sell DR, Monnier V.M. Skin Collagen-Linked Fluorescence Predicts Atherosclerosis Progression in the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. Diabetes (in press).