Joan S. Valentine
Joan S. Valentine
Distinguished Research Professor
Systems Biology and Biological Regulation
Young Hall 4037
Young Hall 4064 & 4033
Joan Selverstone Valentine was born in Auburn, California in 1945. She grew up in Cambridge, Massachusetts and received her primary education there at Shady Hill School. Her high school years were spent at Chatham Hall School in Chatham, Virginia. She graduated with degrees in Chemistry from Smith College (B. A.) and Princeton University (Ph.D.), after which she taught for a year at Princeton. In 1972 she moved to Rutgers University, serving as Assistant, and then Associate, Professor of Chemistry. In 1980 she came to UCLA and joined the faculty of the Department of Chemistry and Biochemistry, where she was made Professor in 1981. She served as Departmental Vice Chair for Research and Administration from 1991 to 1994, and was Director of the UCLA Chemistry-Biology Interface Predoctoral Training Program from 1993 to 2001. In addition to her research and teaching activities at UCLA, Professor Valentine served as Associate Editor of the journal Inorganic Chemistry from 1989 to 1995 and as Editor-in-Chief of the American Chemical Society journal Accounts of Chemical Research from 1994 to the present. She has also served on a number of Boards and Advisory committees, including National Library of Medicine Literature Selection Technical Review Committee (2000-2004), the Carnegie Foundation Initiative on the Doctorate Chemistry Advisory Committee (2002-present), the Board of Trustees of the Gordon Research Conferences (2002-2007), the Visiting Committee for the Division of Chemistry and Chemical Engineering, California Institute of Technology (2002-present) and the Board of Directors of the Research Corporation (1986-2004).
Transition Metals, Metalloenzymes, and Oxidative Stress
1. Copper-Zinc Superoxide Dismutase and ALS
The primary objective of our research in this area is to discover how mutations in copper-zinc superoxide dismutase (SOD1) cause familial amyotrophic lateral sclerosis (fALS) and to explore the possibility that CuZnSOD is also linked to sporadic ALS (sALS). Our work has led us to conclude that aggregation of SOD1 protein is correlated with disease and could possibly be causative. In a collaborative project with two other laboratories, we are (1) analyzing the roles aggregates, fibrils, and other abnormal multimers of SOD1 in disease, and (2) exploring the roles of metal ions and metal metabolism in this disease.
2. Redox Balance, Oxidative Stress, and Metal Ion Metabolism in Eukaryotic Cells
In this project, we seek to understand the molecular mechanisms of antioxidant protection of eukaryotic cells. In particular, we are exploring the relationships between antioxidant enzymes, redox balance, and metal metabolism, using the tools of inorganic chemistry, spectroscopy, molecular biology, and yeast genetics. A recent focus has been on the chemistry that enables manganous ion to functionally substitute for superoxide dismutase in many organisms.
NIH Research Career Development Award
UCLA Alpha Chi Sigma Faculty Research
John C. Bailar, Jr. Medal
Accounts of Chemical Research Editor-in-Chief
Cal. Tech. Ernest K. Swift Lecturer
U. of Maryland Rollinson Lecturer
National Academy of Sciences Member
Sehati Sadaf, Clement Matthew H S, Martins Jake, Xu Lei, Longo Valter D, Valentine Joan S, Gralla Edith B Metabolic alterations in yeast lacking copper-zinc superoxide dismutase. Free radical biology & medicine, 2011; .
Lelie Herman L, Liba Amir, Bourassa Megan W, Chattopadhyay Madhuri, Chan Pik K, Gralla Edith B, Miller Lisa M, Borchelt David R, Valentine Joan Selverstone, Whitelegge Julian P Copper and zinc metallation status of copper-zinc superoxide dismutase from amyotrophic lateral sclerosis transgenic mice. The Journal of biological chemistry, 2011; 286(4): 2795-806.
Kim Sun Hee, Park Hyejin, Seo Mi Sook, Kubo Minoru, Ogura Takashi, Klajn Jan, Gryko Daniel T, Valentine Joan Selverstone, Nam Wonwoo Reversible O-O bond cleavage and formation between Mn(IV)-peroxo and Mn(V)-oxo corroles. Journal of the American Chemical Society, 2010; 132(40): 14030-2.
Seetharaman Sai V, Winkler Duane D, Taylor Alexander B, Cao Xiaohang, Whitson Lisa J, Doucette Peter A, Valentine Joan S, Schirf Virgil, Demeler Borries, Carroll Mark C, Culotta Valeria C, Hart P John Disrupted zinc-binding sites in structures of pathogenic SOD1 variants D124V and H80R. Biochemistry, 2010; 49(27): 5714-25.
de Visser Sam P, Valentine Joan Selverstone, Nam Wonwoo A biomimetic ferric hydroperoxo porphyrin intermediate. Angewandte Chemie (International ed. in English), 2010; 49(12): 2099-101.
Barnese Kevin, Sheng Yuewei, Stich Troy A, Gralla Edith B, Britt R David, Cabelli Diane E, Valentine Joan Selverstone Investigation of the Highly Active Manganese Superoxide Dismutase from Saccharomyces cerevisiae. Journal of the American Chemical Society, 2010; .
Chattopadhyay Madhuri, Valentine Joan Selverstone Aggregation of Copper-Zinc Superoxide Dismutase in Familial and Sporadic ALS. Antioxidants & Redox Signaling, 2009; 11(7): 1603-14.
Shaw Bryan F, Lelie Herman L, Durazo Armando, Nersissian Aram M, Xu Guillan, Chan Pik K, Gralla Edith B, Tiwari Ashutosh, Hayward Lawrence J, Borchelt David R, Valentine Joan S, Whitelegge Julian P Detergent-insoluble aggregates associated with amyotrophic lateral sclerosis in transgenic mice contain primarily full-length, unmodified superoxide dismutase-1. The Journal of Biological Chemistry, 2008; 283(13): 8340-50.
Chattopadhyay Madhuri, Durazo Armando, Sohn Se Hui, Strong Cynthia D, Gralla Edith B, Whitelegge Julian P, Valentine Joan Selverstone Initiation and elongation in fibrillation of ALS-linked superoxide dismutase. Proceedings of the National Academy of Sciences of the United States of America, 2008; 105(48): 18663-8.
Barnese Kevin, Gralla Edith B, Cabelli Diane E, Valentine Joan Selverstone Manganous phosphate acts as a superoxide dismutase. Journal of the American Chemical Society, 2008; 130(14): 4604-6.
Potter Soshanna Zittin, Zhu Haining, Shaw Bryan Francis, Rodriguez Jorge A, Doucette Peter A, Sohn Se Hui, Durazo Armando, Faull Kym F, Gralla Edith Butler, Nersissian Aram M, Valentine Joan Selverstone Binding of a single zinc ion to one subunit of copper-zinc superoxide dismutase apoprotein substantially influences the structure and stability of the entire homodimeric protein. Journal of the American Chemical Society, 2007; 129(15): 4575-83.
Shaw Bryan F, Valentine Joan Selverstone How do ALS-associated mutations in superoxide dismutase 1 promote aggregation of the protein? Trends in biochemical sciences, 2007; 32(2): 78-85.
Munroe William, Kingsley Carolyn, Durazo Armando, Gralla Edith Butler, Imlay James A, Srinivasan Chandra, Valentine Joan Selverstone Only one of a wide assortment of manganese-containing SOD mimicking compounds rescues the slow aerobic growth phenotypes of both Escherichia coli and Saccharomyces cerevisiae strains lacking superoxide dismutase enzymes. Journal of inorganic biochemistry, 2007; 101(11-12): 1875-82.
Shaw Bryan Francis, Durazo Armando, Nersissian Aram M, Whitelegge Julian P, Faull Kym F, Valentine Joan Selverstone Local unfolding in a destabilized, pathogenic variant of superoxide dismutase 1 observed with H/D exchange and mass spectrometry. The Journal of biological chemistry, 2006; 281(26): 18167-76.
Valentine Joan Selverstone, Doucette Peter A, Zittin Potter Soshanna Copper-zinc superoxide dismutase and amyotrophic lateral sclerosis. Annual review of biochemistry, 2005; 74(5): 563-93.
Rodriguez Jorge A, Shaw Bryan Francis, Durazo Armando, Sohn Se Hui, Doucette Peter A, Nersissian Aram M, Faull Kym F, Eggers Daryl K, Tiwari Ashutosh, Hayward Lawrence J, Valentine Joan Selverstone Destabilization of apoprotein is insufficient to explain Cu,Zn-superoxide dismutase-linked ALS pathogenesis. Proceedings of the National Academy of Sciences of the United States of America, 2005; 102(30): 10516-21.
Sanchez Raylene J, Srinivasan Chandra, Munroe William H, Wallace Matthew Alan, Martins Jacob, Kao Tina Y, Le Kate, Gralla Edith Butler, Valentine Joan Selverstone Exogenous manganous ion at millimolar levels rescues all known dioxygen-sensitive phenotypes of yeast lacking CuZnSOD. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry, 2005; 10(8): 913-23.
Wallace Matthew Alan, Bailey Sasaneh, Fukuto Jon M, Valentine Joan Selverstone, Gralla Edith Butler Induction of phenotypes resembling CuZn-superoxide dismutase deletion in wild-type yeast cells: an in vivo assay for the role of superoxide in the toxicity of redox-cycling compounds. Chemical research in toxicology, 2005; 18(8): 1279-86.