AUGUST 2009 VOLUME 22, NUMBER 8 Copyright 2009 by the American Chemical Society
In Memoriam: Lawrence (Larry) M. Sayre
Our friend and colleague, Lawrence (Larry) M. Sayre, died May 8, 2009, in Cleveland, Ohio, at the age of 57. Larry will be deeply missed as a friend, a scientist, and a pillar of Case Western Reserve University. Larry received his undergraduate degree with highest honors from UCSD and his Ph.D. from the University of California, Berkeley. After spending a year at Vega Biochemicals in Tucson and then 3 years as a postdoctoral researcher in medicinal chemistry at the University of Minnesota, he joined the Chemistry Department at Case Western Reserve University (CWRU), rose through the ranks to become
Frank Hovorka Professor and Chair of the Chemistry Department, and also held professorial appointments in the Departments of Pathology and Environmental Health Sciences at the time of his sudden illness. Recognizing his tactful and fair management style, the university conscripted him to be Interim Chair of the Department of Modern Languages and Literatures from 2006 to 2008. Larry’s research bridged the fields of organic chemistry, medicinal chemistry, and biochemistry. During his 27 year career at CWRU, he published more than 190 research papers,
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served on NIH Study Sections, and participated in the LongRange Planning Committee for the Medicinal Chemistry Division of the American Chemical Society. He served twice on the Editorial Board of Chemical Research in Toxicology (1998-2000 and 2006-2008) and published 22 articles, one of which (co-authored by George Perry and Mark Smith) was among the journal’s most widely read papers in 2008. A hard-working and brilliant scientist, he represented all that our school and university strive for in terms of collegiality and excellence. Larry’s creative approach to research and his insight into mechanisms of protein damage will be sorely missed by his many colleagues. His discoveries on the involvement of protein modification by products of lipid oxidation in diabetes and cardiovascular and neurological diseases emerged from his insightful ideas, questions, and hypotheses. Larry’s impact was multiplied by a knack for engaging other chemists and biomedical researchers in cooperative endeavors. In particular, at CWRU, he collaborated with Charles Hoppel (on mitochondrial dysfunction), Pierluigi Gambetti (on chemical modifications of neuronal proteins), George Perry and Mark Smith (on chemical modifications of β-amyloid in Alzheimer’s disease), Miriam Weiss and Ram Nagaraj (on protein damage in end stage renal disease and cataract, respectively), and Vincent Monnier (on protein modifications by glycation in diabetes and aging). He was a co-founder of the Protein Aging Group with Vincent Monnier. Larry and I collaborated with Cleveland Clinic Foundation (CCF) researchers Eugene Podrez and Henry Hoff on the role of lipid oxidation in atherosclerosis. Mark Smith told me, “I will always remember, and continue to strive for, his insistence on rigor and thoroughness, which ultimately results in excellence. What I loved about Larry, aside from his summer wardrobe of garish Hawaiian shirts and requisite humor to wear such stuff, was his willingness to listen to complete and utter nonsensical chemistry talk from me and gently set me straight.” Pierluigi Gambetti affectionately echoed these sentiments observing that, “Larry had a relaxed attitude but invariably accurate knowledge.” Vincent Monnier said, “Larry’s participation as a co-investigator in numerous research programs on campus and at the CCF resulted in many Cleveland investigators being successful recipients of NIH grants, illustrating thereby how pivotal and literally irreplaceable he was as a scientist.” Referring to his collaborative studies with Larry and their impact on the molecular mechanisms underlying the most common disease in this countryscardiovascular diseasesEugene Podrez said, “it was comfortable for me as a person trained mostly in cell biology and biochemistry to approach this scientific problem together with somebody possessing a deep understanding of chemistry. Most importantly, the pure academic knowledge that we acquired from our collaborative studies may be applied in the future for creation of antagonists preventing the development of cardiovascular disease.” Vernon Anderson remembers Larry as, “a great collaborator and friend. He imposed the rigor of chemistry on those of us who would occasionally fall for the biologists rush to conviction (HNE Schiff bases come to mind). There was always the unspoken guidepost, ‘Will Larry be convinced?’ Larry’s support, suggestions, collaboration and friendship during my years at CWRU will remain with me forever as the prime example of what a University community could and should be.”
Ian Blair (University of Pennsylvania) commented that, “Larry was one of the most delightful scientists that it has been my pleasure to interact with. His important work on the modification of proteins by lipid-derived reactive aldehydes has been an inspiration to many of us in the field. His attention to detail and the rigor of the structural analyses that he performed will represent a landmark for many years to come. I was fortunate by chance to have lunch with him at the 2007 Fall ACS meeting in Boston in what turned out to be my final meeting with him. I will treasure the memory of that final meeting forever. It was during that lunch I learned of his astonishing and selfless contribution to CWRU in becoming Interim Chair of Modern Languages and Literature. Larry’s creative approach to research and his insight into mechanisms of protein damage will be sorely missed by me and my colleagues.” The far-reaching consequences of Larry’s curiosity about the fundamental chemistry of biomolecules are epitomized by his investigation of the reaction of the lipid oxidation product 4-hydroxy-2-nonenal with proteins. In a model study, he discovered that primary amines are converted into 2-pentylpyrroles and enlisted me to help him show that this chemistry occurs with proteins in vivo (1). With George Perry and Mark Smith, we found accumulation of these protein modifications in Alzheimer’s brain and Alexander’s disease (2, 3). The chemistry he discovered inspired remarkable breakthroughs in our understanding of age-related macular degeneration involving many researchers at the Cole Eye Institute of the Cleveland Clinic Foundation. We found that proteins modified with certain lipidderived pyrroles accumulate in the retinas of individuals with AMD (4) where they induce angiogenesis into the retina (5) and trigger an immune response that results in retinal degeneration (6). Larry was a talented pianist and an avid jazz lover, in both performance and listening, and evenings out generally focused on those establishments that had live musical entertainment. Both Mike and I had the privilege of developing lasting friendships with Larry, and we often traveled together and spoke about our families. A genuine and very approachable person, Larry cared about the people with whom he worked. He is deeply missed. His impact on the lives of his colleagues, students, and friends was profound, and the memory of this gentle man inspires us all. Robert Salomon Michael Zagorski
References (1) Sayre, L. M., Sha, W., Xu, G., Kaur, K., Nadkarni, D., Subbanagounder, G., and Salomon, R. G. (1996) Immunochemical evidence supporting 2-pentylpyrrole formation on proteins exposed to 4-hydroxy-2-nonenal. Chem. Res. Toxicol. 9, 1194–1201. (2) Castellani, R. J., Perry, G., Harris, P. L., Cohen, M. L., Sayre, L. M., Salomon, R. G., and Smith, M. A. (1998) Advanced lipid peroxidation end-products in Alexander’s disease. Brain Res. 787, 15–18. (3) Sayre, L. M., Zelasko, D. A., Harris, P. L., Perry, G., Salomon, R. G., and Smith, M. A. (1997) 4-Hydroxynonenal-derived advanced lipid peroxidation end products areincreased in Alzheimer’s disease. J. Neurochem. 68, 2092–2097. (4) Crabb, J. W., Miyagi, M., Gu, X., Shadrach, K., West, K. A., Sakaguchi, H., Kamei, M., Hasan, A., Yan, L., Rayborn, M. E., Salomon, R. G., and Hollyfield, J. G. (2002) Drusen proteome analysis: An approach to the etiology of age-related macular degeneration. Proc. Natl. Acad. Sci. U.S.A. 99, 14682–14687.
Chem. Res. Toxicol., Vol. 22, No. 8, 2009 1371 (5) Ebrahem, Q., Renganathan, K., Sears, J., Vasanji, A., Gu, X., Lu, L., Salomon, R. G., Crabb, J. W., and Anand-Apte, B. (2006) Carboxyethylpyrrole oxidative protein modifications stimulate neovascularization: Implications for age-related macular degeneration. Proc. Natl. Acad. Sci. U.S.A. 103, 13480–13484.
(6) Hollyfield, J. G., Bonilha, V. L., Rayborn, M. E., Yang, X., Shadrach, K. G., Lu, L., Ufret, R. L., Salomon, R. G., and Perez, V. L. (2008) Oxidative damage-induced inflammation initiates age-related macular degeneration. Nat. Med. 14, 194–198.
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