AASLD 2006 distinguished achievement award to Neil Kaplowitz
Authors: Laurie DeLeve
Journal: Hepatology (2006)

His laboratory has discovered and characterized proteins that bind xenobiotics and endobiotics and that are responsible for their transfer within the cell. He has discovered and characterized the transport of glutathione (GSH), and the key role hepatic GSH transport plays in the regulation of inter-organ homeostasis of cysteine and GSH in the brain, kidney, intestine, and immune system, as well as the role of hepatic GSH transport in bile secretion. Neil has uncovered the mechanism of GSH sequestration in mitochondria and the key role of mitochondrial GSH in cell survival in an aerobic environment. His laboratory discovered the selective impairment of GSH transport into mitochondria in the chronic alcoholic liver, which sensitizes hepatocytes to cytokine-induced cell death. Neil's laboratory has characterized cell death pathways including the targeting of death receptors to the cell surface and the important therapeutic implications of this finding. His papers have demonstrated the importance of oxidative stress and redox perturbations in impairing transcriptional regulation of survival gene expression. His research has focused on mechanisms of drug hepatotoxicity, in particular of acetaminophen, with the discovery of the dominant role of stress kinases and of the role of the innate immune system in determining organ damage. Finally, he has recently discovered the role of hyperhomocysteinemia and of endoplasmic reticulum stress in the pathogenesis of alcohol-induced injury to the liver. His work has provided numerous novel scientific concepts and because of the high caliber of his research, these concepts have withstood the test of time. Each of Neil's papers is a gem, a complete exploration of a question from all angles and in different models. Neil was born in New York and went to Stuyvesant High School. He received his B.S., cum laude, and his M.D. from New York University. As a senior medical student, Neil did a 6-month elective with Dr. Norman Javitt at NYU. This resulted in his very first paper: he was first author of a paper published in the New England Journal of Medicine. During the first year of his GI Fellowship, he did research in Attalah Kappas' laboratory at Rockefeller University. He continued his research with Norman Javitt for the next 2 years. By the time Neil finished his GI Fellowship, he had already published 7 research papers, 6 as first author. He began his career as an independent investigator while he fulfilled his service requirement in the Navy by doing research, as part of the Berry plan, at the Clinical Investigation Center of the Oakland Naval Hospital. After the Navy, Neil was recruited by Jon Isenberg and Morton Grossman to be Chief of Hepatology at the UCLA/Wadsworth VA. Within 5 years he was Chief of Gastroenterology and Hepatology at UCLA/Wadsworth VA. He remained at UCLA until 1990, when he assumed his current position as Chief of the Division of Gastrointestinal and Liver Diseases at the University of Southern California Keck School of Medicine. When I asked Neil about the people who shaped him as a scientist, he said his mentors were Attalah Kappas and Norman Javitt. Neil considers Dr. Javitt's mentorship the single most important factor shaping his research career. His five major role models have been: Rudi Schmid, who inspired him with his kindness to young investigators and his brilliant career; Irwin Arias, for his creativity and scientific longevity; James Boyer, as a clinician and a scientist; Alton Meister, the father of GSH; and Hyman Zimmerman, the pioneer of drug-induced liver injury. Four close colleagues in particular have influenced him, notably Morton Grossman, Jon Isenberg, George Sachs, and John Walsh. Neil's mentorship has inspired numerous young MDs and PhDs and he has trained them in his mold. His mentees and protégées have made invaluable contributions to Hepatology, thereby multiplying Neil's ultimate contributions to the field. He has trained 72 postdoctoral Fellows and graduates students so far. His kindness and thoughtfulness inspire tremendous loyalty and affection among those of us who were trained by him, although that is not unique to his mentees. Wherever I travel, his colleagues speak with great fondness of Neil. Many of his mentees are now academically successful in their own right: Tadataka Yamada, Yuichi Sugiyama, Andrew Stolz, Tak Yee Aw, Hajime Takikawa, Robert Gish, José Fernandez-Checa, Shelly Lu, Stuart Sherman, Laurie DeLeve, and Estella Alonso, to name a few. Why have so many of Neil's protégées gone on to academic success? This relates to his style as a teacher of scientists and his amazing generosity with time and resources, which allows those who work with him to thrive. He allows the young people in his laboratory the freedom to develop their own ideas, but counterbalances this with weekly lab meetings that provide ample time to examine the data in depth. Neil has an uncanny ability to problem-solve during lab meetings. Perhaps most importantly, lab meetings are where Neil teaches how to examine a question with various approaches and in a variety of models, with a constant goal of ensuring the validity of the data. Neil is unstintingly generous with research space and funds, giving unfunded investigators their own laboratories, at the expense of his own space, and giving them the resources to be productive. Neil has published 162 peer-reviewed papers, 118 chapters and reviews, and has edited or co-edited 13 books. He has compiled and edited two multi-author textbooks: "Liver and Biliary Diseases" and "Drug-Induced Liver Disease". He has been Associate Editor of Hepatology, Gastroenterology, the American Journal of Physiology, co-editor of Hepatology Highlights, and has served on the editorial board of the Journal of Biological Chemistry. He was on the Council of AASLD from 1993-2000 and President of AASLD in 1998. He was elected to Phi Beta Kappa and Alpha Omega Alpha and is a member of the American Society of Clinical Investigation and the Association of American Physicians. He received an NIH Merit Award in 1992, the Veteran Administration's William S. Middleton Award and he was an AGA Foundation Research Mentor Award Honoree last year. Finally, and most deservedly, on October 30th, in the presence of his wife Fattaneh; his children Hillary, Greg, and Daria; his sister Norma; and his cousin Barbara, Neil Kaplowitz received the 2006 AASLD Distinguished Achievement Award.