Richard A. Lerner
Richard A. Lerner is a research chemist, best known for his work on catalytic antibodies, Lerner served as President of The Scripps Research Institute (TSRI) until January 1, 2012, and is currently a member of its Skaggs Institute for Chemical Biology, in La Jolla, California.
Lerner grew up in Chicago and excelled at chemistry and wrestling as a schoolboy. After attending Northwestern University as an undergraduate, Lerner obtained an MD from Stanford Medical School in 1964 then undertook postdoctoral training at Scripps Clinic and Research Foundation, an early incarnation of the institute he would eventually lead. In the 1970s Lerner carried out research at the Wistar Institute in Philadelphia then returned to La Jolla to the now renamed Research Institute of Scripps Clinic. In 1982 he was appointed chairman of the Department of Molecular Biology, then five years later assumed the directorship. In 1991, when the TSRI was established as a nonprofit entity, Lerner became its first president.
In addition to his research into catalytic antibodies, providing a method of catalyzing chemical reactions thought impossible using classical techniques, Lerner has led extensive studies into protein structure, characterised cis-9,10-octadecenoamide, a novel lipid hormone that induces sleep, and provided the first evidence of a role for ozone in human disease. In 1967 Lerner discovered the role of anti-GBM antibodies in the pathogenesis of Goodpasture's disease. As of 2007, Lerner's résumé listed 67 patents and 403 published scientific papers.
Lerner is the Lita Annenberg Hazen Professor of Immunochemistry and Cecil H. and Ida M. Green Chair in Chemistry. He has been the recipient of over 29 honors and prizes. These include the Parke-Davis Award in 1978, the San Marino Prize in 1990, the Wolf Prize in Chemistry for 1994 (with Peter Schultz). He was the Myron L. Bender and Muriel S. Bender Summer Lecturer at Northwestern University in 1994 as well. Richard Lerner was awarded the California Scientist of the Year Award in 1996 and the University of California Presidential Medal in 2002. He has also been elected to the Royal Swedish Academy of Sciences and the United States National Academy of Sciences. In 2010 he was awarded an honorary degree from the University of Warwick to add to those he received from Technion – Israel Institute of Technology in 2001, Ben-Gurion University of the Negev in 2003 and Florida Atlantic University in 2004 and University of Oxford in 2007. Richard Lerner shared the 2012 Prince of Asturis award, that is often called the Spanish Nobel Prize, with Sir Gregory Winter for his conception and development of combinatorial antibody libraries.
- (2016). Robotic QM/MM-driven maturation of antibody combining sites. Sci Adv 2 (10), e1501695 [+]
In vitro selection of antibodies from large repertoires of immunoglobulin (Ig) combining sites using combinatorial libraries is a powerful tool, with great potential for generating in vivo scavengers for toxins. However, addition of a maturation function is necessary to enable these selected antibodies to more closely mimic the full mammalian immune response. We approached this goal using quantum mechanics/molecular mechanics (QM/MM) calculations to achieve maturation in silico. We preselected A17, an Ig template, from a naïve library for its ability to disarm a toxic pesticide related to organophosphorus nerve agents. Virtual screening of 167,538 robotically generated mutants identified an optimum single point mutation, which experimentally boosted wild-type Ig scavenger performance by 170-fold. We validated the QM/MM predictions via kinetic analysis and crystal structures of mutant apo-A17 and covalently modified Ig, thereby identifying the displacement of one water molecule by an arginine as delivering this catalysis.ID:1605