Appendix C
New Classes of Antimicrobials Workshop

NEW DIRECTIONS IN THE STUDY OF ANTIMICROBIAL THERAPEUTICS: NEW CLASSES OF ANTIMICROBIALS


May 23-24, 2005

Keck Center of the National Academies • Room 201

500 Fifth Street, N.W. • Washington, D.C. 20001

AGENDA

Monday, May 23, 2005

8:00 a.m.

Continental Breakfast

8:30 a.m.

Opening Remarks and Introductions

 

Christopher T. Walsh (Committee Chair), Harvard Medical School

 

Michael G. Kurilla, Director, Office of Biodefense Research Affairs, National Institute of Allergy and Infectious Diseases, NIH

 

Workshop Participants



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Treating Infectious Diseases in a Microbial World: Report of Two Workshops on Novel Antimicrobial Therapeutics Appendix C New Classes of Antimicrobials Workshop NEW DIRECTIONS IN THE STUDY OF ANTIMICROBIAL THERAPEUTICS: NEW CLASSES OF ANTIMICROBIALS May 23-24, 2005 Keck Center of the National Academies • Room 201 500 Fifth Street, N.W. • Washington, D.C. 20001 AGENDA Monday, May 23, 2005 8:00 a.m. Continental Breakfast 8:30 a.m. Opening Remarks and Introductions   Christopher T. Walsh (Committee Chair), Harvard Medical School   Michael G. Kurilla, Director, Office of Biodefense Research Affairs, National Institute of Allergy and Infectious Diseases, NIH   Workshop Participants

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Treating Infectious Diseases in a Microbial World: Report of Two Workshops on Novel Antimicrobial Therapeutics 9:20 a.m. The Clinical Impact of Antimicrobial Resistance   Robert C. Moellering, Jr., Harvard Medical School and Beth Israel Deaconess Medical Center 9:50 a.m. Questions and Discussion 10:15 a.m. The Question of Resistance: What It Is, Why It Develops, and How to Circumvent It   Gerard D. Wright, McMaster University 10:45 a.m. Questions and Discussion 11:10 a.m. Break 11:30 a.m. Antibiotics: Past, Present, and Future   Christopher T. Walsh, Harvard Medical School 12:00 p.m. Questions and Discussion 12:25 p.m. Lunch 1:10 p.m. Discovery of Antimicrobials: From Targets to the Clinic   Molly Schmid, Keck Graduate Institute 1:50 p.m. Questions and Discussion 2:15 p.m. Applying Ecological and Evolutionary Theory to Meet the Challenge of Antibiotic Resistance   Margaret Riley, University of Massachusetts-Amherst 2:45 p.m. Questions and Discussion 3:10 p.m. Break 3:20 p.m. Molecular Detection and Diagnosis: The Role of Detection and Rapid Diagnosis in Treating Infectious Disease   Francis Barany, Weill Medical College of Cornell University 3:50 p.m. Questions and Discussion

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Treating Infectious Diseases in a Microbial World: Report of Two Workshops on Novel Antimicrobial Therapeutics 4:15 p.m. Small group discussions to organize topics for Tuesday breakout sessions 5:00 p.m. Small group reports and discussion 5:45 p.m. Adjourn for the day Tuesday, May 24, 2005 8:30 a.m. Plan of action for the day and any new issues since Monday 9:00 a.m. Working breakout group discussions of key areas   Identify the most promising areas, hurdles to overcome, needed research and clarification 11:00 a.m. Breakout group 1 report 11:20 a.m. Discussion 11:45 a.m. Breakout group 2 report 12:05 p.m. Discussion 12:30 p.m. Lunch 1:00 p.m. Breakout group 3 report 1:20 p.m. Discussion 1:45 p.m. Breakout group 4 report 2:05 p.m. Discussion 2:30 p.m. Break 2:45 p.m. General discussion and conclusions 4:00 p.m. Adjourn

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Treating Infectious Diseases in a Microbial World: Report of Two Workshops on Novel Antimicrobial Therapeutics Breakout Group Topics New molecules: Where do new anti-infective chemical entities come from and what are their desired characteristics? (What do you screen?) Ecological interactions: What are the underlying principles of ecological interactions to exploit or interrupt for the development of new therapies? Resistance: How do we minimize it and extend the lifetime of the next generation of antibiotics, including the appropriate use of diagnostics? Biological processes: What are the biological approaches that will inform new strategies for finding new antibiotics? Participants Rustom Antia, Emory University Francis Barany, Weill Medical College of Cornell University Bonnie L. Bassler, Princeton University (member of committee) Carl Bergstrom, University of Washington Martin J. Blaser, New York University Eric Brown, McMaster University Richard R. Burgess, University of Wisconsin Jon Clardy, Harvard Medical School Don Clewell, University of Michigan (retired) Julian Davies, University of British Columbia Rob Dorit, Smith College Ferric C. Fang, University of Washington and Harborview Medical Center Lou Gross, University of Tennessee Pehr A.B. Harbury, Stanford University Roberto Kolter, Harvard Medical School Walter P. Lowe, Howard University Robert C. Moellering, Jr., Harvard Medical School and Beth Israel Deaconess Medical Center Carl Nathan, Weill Medical College of Cornell University (member of committee)

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Treating Infectious Diseases in a Microbial World: Report of Two Workshops on Novel Antimicrobial Therapeutics Thomas F. O’Brien, Brigham and Women’s Hospital (member of committee) John H. Rex, AstraZeneca Pharmaceuticals Margaret Riley, University of Massachusetts-Amherst (member of committee) Marty Rosenberg, Promega Corporation Molly B. Schmid, Keck Graduate Institute K. Barry Sharpless, The Scripps Research Institute Peter M. Small, Bill and Melinda Gates Foundation Anne Summers, University of Georgia Joyce Sutcliffe, Rib-X Pharmaceuticals Saeed Tavazoie, Princeton University Julie Theriot, Stanford University Christopher T. Walsh, Harvard Medical School (chair of committee) Janet Westpheling, University of Georgia Richard J. White, Vicuron Pharmaceuticals (member of committee) Gerard D. Wright, McMaster University (member of committee) Observers from the National Institute of Allergy and Infectious Diseases, NIH Susan Daniels (microbiology) Judith Hewitt (animal model drug testing) Michael G. Kurilla (biodefense) N. Kent Peters (antimicrobial resistance) John Prakash (regulatory affairs) Helen Quill (immunology) John Rogers (parasitology) Katherine A. Taylor (enteric pathogens and toxins) David Winter (immunology) anling Zou (bacteriology) Staff from the National Academies Board on Life Sciences Adam P. Fagen, Program Officer Joe Larsen, Postdoctoral Research Associate Matt McDonough, Program Assistant Ann Reid, Program Officer Robert Yuan, Consultant; Professor of Cell Biology & Molecular Genetics, University of Maryland

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Treating Infectious Diseases in a Microbial World: Report of Two Workshops on Novel Antimicrobial Therapeutics Speaker Biographical Sketches Francis Barany received his Ph.D. in Microbiology in 1981 at The Rockefeller University with Professor Alexander Tomasz. He was a Helen Hay Whitney postdoctoral fellow with Professor Hamilton O. Smith at the Johns Hopkins University School of Medicine from 1982-1985. Upon appointment as an Assistant Professor in Microbiology at Weill Medical College of Cornell University in 1985, he was named a Cornell Scholar in Biomedical Sciences, and in 1992 received a five year Hirschl/Monique Weill-Caulier Career Scientist Award. He currently holds the rank of Full Professor in the Department of Microbiology and Program of Biochemistry and Structural Biology at Cornell/Sloan Kettering Institute. He has an adjunct appointment at The Rockefeller University in the Department of Chemistry, Biochemistry, and Structural Biology, as well as an appointment as Director of Mutation Research at the Strang Cancer Prevention Center. He is program director of two multi-center NCI and NIAID grants to develop new methods of cancer and infectious disease detection. He is best known for developing the ligase chain reaction (LCR) and ligase detection reaction (LDR) and Universal DNA arrays for detection of genetic diseases and cancer-associated mutations. He was honored as Medical Diagnostics Research leader, Scientific American 50, in 2004. Robert C. Moellering, Jr., M.D., is the Herrman L. Blumgart Professor of Medicine at Harvard Medical School and Physician-in-Chief and Chairman of the Department of Medicine at the Beth Israel Deaconess Medical Center, Boston, MA. Dr. Moellering received his medical degree cum laude from Harvard Medical School and postgraduate training at Massachusetts General Hospital where he was also a Fellow in Infectious Diseases. He served as Chairman of the Department of Medicine at the Deaconess Hospital in Boston from 1981 through 1996. Dr. Moellering is the recipient of several awards, including an honorary Doctor of Science degree from Valparaiso University, the Garrod Medal from the British Society for Antimicrobial Chemotherapy, the Feldman Award and the Finland Award from the Infectious Diseases Society of America and the Hoechst-Roussel Award from the American Academy of Microbiology. Dr. Moellering is a Fellow of the Infectious Diseases Society of America and a Master of the American College of Physicians, is an Honorary Fellow of the Royal College of Physicians and has been elected to membership in

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Treating Infectious Diseases in a Microbial World: Report of Two Workshops on Novel Antimicrobial Therapeutics the American Society for Clinical Investigation and the Association of American Physicians. Dr. Moellering has authored more than 350 publications and is Editor-in-Chief Emeritus of Antimicrobial Agents and Chemotherapy, Editor of Infectious Disease Clinics of North America and Editor of the European Journal of Clinical Microbiology and Infectious Diseases. Margaret Riley is a Professor of Biology at the University of Massachusetts Amherst. She received her Ph.D. in population genetics from Harvard University and performed postdoctoral research in microbial population genetics with a Sloan Postdoctoral Fellowship in Molecular Evolution. She joined the faculty at Yale in 1991 and recently moved to UMass Amherst. She has a broad set of research interests that range from studies of experimental evolution of microbes to developing novel antimicrobials and redefining the microbial species concept. Dr. Riley studies the evolution of microbial diversity, with a particular emphasis on the ecology and evolution of microbial toxins. Her recent work has revealed that the production of toxins is a primary force in the generation and maintenance of microbial diversity. These studies led to an interest in applying ecological and evolutionary theory to the design of novel antimicrobials for use in animal and human health. She is co-founder of Origin Antimicrobials, Inc., whose mission is to discover and refine novel antimicrobials to address the challenge of antibiotic resistance. Dr. Riley is the Director of the Organismic and Evolutionary Biology Program and the Director of the Museum of Natural History at UMass Amherst. From 1999-2002 she chaired the Gordon conference on molecular evolution and from 2003-2005 she chaired the Gordon conference on microbial population biology and evolution. She is a fellow of the American Academy of Microbiologists. Molly B. Schmid, Ph.D., joined the Keck Graduate Institute (Claremont CA) in January 2005, as Jacobs Professor and Entrepreneur-in-Residence. At KGI, she teaches “Risks & Rewards in Drug Discovery & Development” and continues to explore her interests in chemical genetics and antimicrobial drug discovery. Formerly, she was Senior Vice President of Preclinical Programs at Affinium Pharmaceuticals (Toronto, ON); Senior Director, Functional Genomics & Bioinformatics at Genencor International (Palo Alto, CA); and Vice President, Research Alliances with Microcide Pharmaceuticals (Mountain View, CA). From 1986-1994, she was Assistant Professor of Molecular Biology at Princeton University where her lab investigated bacterial chromosome structure and function, and her

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Treating Infectious Diseases in a Microbial World: Report of Two Workshops on Novel Antimicrobial Therapeutics research group discovered Topoisomerase IV in Salmonella typhimurium, as well as a genetic strategy for identifying new antimicrobial targets. She is a Fellow of the American Academy of Microbiology, a Searle/Chicago Community Trust Scholar and a Damon Runyon-Walter Winchell Fellow. She received her Ph.D. in Biology from the University of Utah, and her B.S. from SUNY Albany. Christopher T. Walsh is the Hamilton Kuhn Professor of Biological Chemistry and Molecular Pharmacology (BCMP) at Harvard Medical School. He has had extensive experience in academic administration, including Chairmanship of the MIT Chemistry Dept (1982-1987) and the HMS Biological Chemistry & Molecular Pharmacology Dept (1987-1995) as well as serving as President and CEO of the Dana Farber Cancer Institute (1992-1995). His research has focused on enzymes and enzyme inhibitors, with recent specialization on antibiotics. He and his group have authored over 600 research papers, books on Enzymatic Reaction Mechanisms (1979); Antibiotics: Origins, Actions, Resistance (2003); Posttranslational Modification of Proteins: Expanding Nature’s Inventory (2005). He is a member of the National Academy of Sciences, the Institute of Medicine, and the American Philosophical Society. He has been a consultant to government and academic institutions, including NIGMS, and a Trustee of the Whitehead Institute and the Helen Hay Whitney Foundation. He has been a consultant to large pharmaceuticals (Merck, Roche, and Abbot), and been involved in scientific advisory capacity for Genzyme, Immunogen, Leukosite, Kosan Biosciences, Millennium, Versicor, Transform Pharmaceuticals, Critical Therapeutics, and MPM capital. He sits on the Board of Directors of Critical Therapeutics, Kosan, Microbia, and Vicuron. At HMS he has recently served as co-chair of a committee to review the HMS Conflict of Interest policies. He is chair of the executive committee of the Harvard Integrated Life Sciences graduate programs. Gerard D. Wright is Professor and Chair of the Department of Biochemistry and Biomedical Sciences at McMaster University, Hamilton, Ontario, and the Director of the McMaster Antimicrobial Research Centre. He received his B.Sc. in Biochemistry (1986) and his Ph.D. in Chemistry (1990) from the University of Waterloo. He followed this up with 2 years of postdoctoral research at Harvard Medical School in Boston and joined the De-

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Treating Infectious Diseases in a Microbial World: Report of Two Workshops on Novel Antimicrobial Therapeutics partment of Biochemistry at McMaster in 1993. He holds a Canada Research Chair in Antibiotic Biochemistry and has received Canadian Institutes of Health Research Scientist (2000-2005) and Medical Research Council of Canada Scholar (1995-2000), Premiers’ Research Excellence (1999) and Polanyi Prize (1993) awards. He is a member of the Canadian Bacterial Diseases Network Centre of Excellence and the Director of the American Chemical Society Short Course on Antibiotics and Antibacterial Agents. Dr. Wright is co-founder, with Dr. Eric Brown, of the McMaster High Throughput Screening Facility. Dr. Wright’s laboratory conducts research on the molecular mechanisms of antibiotic resistance including resistance to aminoglycoside, glycopeptide and streptogramin families of antibiotics, on the mechanisms of antibiotic biosynthesis, and on the discovery of new antimicrobial targets, in particular antifungal agents. He is the author of over 90 published papers and book chapters.

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