A team of antibiotic discovery experts from around the world has collaborated with The Pew Charitable Trusts to help build its Shared Platform for Antibiotic Research and Knowledge (SPARK), which uses technology developed by Collaborative Drug Discovery, Inc. The experts will continue to review and analyze SPARK data, and use the SPARK platform to generate new research models and hypotheses, and propose studies. This research could help answer long-standing scientific questions about how molecules enter and remain inside of Gram-negative bacteria, which are responsible for some of the world’s most dangerous and hardest-to-treat resistant infections.
The discovery experts meet regularly and collaborate in subgroups to assess different aspects of SPARK and help optimize the platform’s usability and potential impact.
Arthur Campbell is a computational chemist in the Medicinal Chemistry Group of the Stanley Center for Psychiatric Research at the Broad Institute of the Massachusetts Institute of Technology and Harvard University. He is also skilled in drug design and discovery, molecular dynamics, medicinal chemistry, and structural biology.
Campbell received a bachelor’s degree in chemistry from Stony Brook University in New York, where he also received a doctorate in computational chemistry under the mentorship of Carlos Simmerling and Orlando Schärer. He was awarded an IGERT 3MT trainee scholarship from the National Science Foundation in support of his doctoral studies. Campbell undertook a postdoctoral fellowship at AstraZeneca’s Infection iMed unit, where he later took a post as senior scientist. In 2013, he was awarded the AstraZeneca Emerging Scientist of the Year award for his work there. He joined the Broad Institute in 2014.
Alice Erwin is an infectious disease microbiologist with experience in academic and industrial settings. Her scientific research over the past 30 years has revolved around the structure and function of bacterial membranes, with particular interest in antibiotic resistance of Gram-negative bacteria. She held senior positions in programs at PathoGenesis Corp., Chiron Corp., and Vertex Pharmaceuticals Inc. seeking to discover drugs for the treatment of bacterial infections. Today Erwin is an independent scientific consultant, providing advice on the technical and strategic aspects of antibiotic discovery to academic and industrial research groups. Her expertise includes all stages of drug discovery, from development of an overall strategy through target selection, screening and hit evaluation (screening for promising molecules) to discovery and optimization of a lead chemical series. A key component of her skill as a consultant is the insight she has gained as a reviewer of drug discovery grant proposals in over 25 National Institutes of Health (NIH) study sections. She has a clear understanding of the difficulties that academics and small-business groups face when seeking to translate their research into drugs that will fill an unmet medical need.
She holds a bachelor’s degree in microbiology and a master’s degree in pathobiology, both from the University of Washington, and a doctorate in microbiology from the University of Texas Southwest Medical Center, Dallas. She also held a postdoctoral fellowship at The Rockefeller University.
Paul Hergenrother established his laboratory in 2001 in the department of chemistry at the University of Illinois, Urbana-Champaign, where he currently holds the Kenneth L. Rinehart endowed chair in natural products chemistry. The Hergenrother lab uses small molecules to identify and validate novel targets for the treatment of intractable diseases, including cancer and multidrug-resistant bacteria. The lab discovered the first compound (PAC-1) to directly activate procaspase 3 (a protein that triggers self-destruction in cancer cells), which has been used by many labs as a tool for further study and is being evaluated in clinical trials in cancer patients. His lab also discovered the potent anti-cancer activity of the natural product deoxynyboquinone (DNQ) and has demonstrated the tremendous selectivity of DNQ for cancer cells. The lab reported a novel method for rapid construction of complex and diverse compounds starting from natural products, and this compound collection was used to develop predictive guidelines for compound accumulation in Gram-negative bacteria.
Hergenrother received his bachelor’s degree in chemistry from the University of Notre Dame, his doctorate in chemistry from the University of Texas, Austin, and was an American Cancer Society postdoctoral fellow at Harvard University.
Richard Lee is a faculty member and interim chair of the department of chemical biology and therapeutics at St. Jude Children’s Research Hospital, and an adjunct professor of pharmaceutical sciences at the University of Tennessee Health Science Center. At St. Jude, his research focuses on anti-infective medicinal chemistry and structure-based drug design, with an emphasis on creating new inhibitors to treat chronic drug-resistant bacterial infections. His expertise is recognized by frequent service on many government and industrial advisory panels. He was co-chair of the 2018 Gordon Research Conference on New Antibacterial Discovery and Development. He is also actively involved in advocating for development of new antibiotics and how this can be addressed from a chemistry perspective.
He received a doctorate in organic chemistry from the University of Newcastle-upon-Tyne, United Kingdom, and held postdoctoral research fellowship positions in microbiology at Colorado State University, and chemistry at Oxford University, United Kingdom. He was also a research scientist at the National Institute of Allergy and Infectious Diseases, NIH.
Andy Merritt has been the head of chemistry at the LifeArc (formerly MRC Technology) Centre for Therapeutics Discovery since 2009. In close collaboration with academic scientists, LifeArc develops and subsequently pursues innovative drug discovery programs emerging from academic research. In his previous position, Merritt was a director of medicinal chemistry discovery with GlaxoSmithKline. Between 1995 and 2001, as part of the Glaxo Wellcome organization, he led interdisciplinary teams focusing on discovery and optimization, and incorporating the development of new chemical technologies. Merritt joined the former Glaxo organization as a senior medicinal chemist in 1988 following postdoctoral studies in the U.S., and initially worked on oncology and pain drug discovery programs, leading to one clinical drug candidate submission. Merritt sits on the Royal Society of Chemistry’s magazine editorial board and has been a regular undergraduate lecturer in pharmaceutical medicine at Imperial College London and the universities of Warwick and Sussex.
He holds bachelor’s and doctoral degrees in chemistry from Imperial College London. He also held a postdoctoral fellowship at Indiana University, Bloomington.
As director of medicinal chemistry with the Center for the Science of Therapeutics at the Broad Institute of Harvard University and the Massachusetts Institute of Technology, Marshall Morningstar was involved in directing a portfolio of neglected disease efforts. Before joining Broad, he was the head of chemistry for collaborative discovery efforts for GVK BIO, directing multiple programs in metabolic disorders, pain, and oncology research. His passion for antibacterial research stems from his 11 years in the AstraZeneca infection group. Specifically, he chaired the FastFollower team and led medicinal chemistry on a program that led to AstraZeneca/Entasis Therapeutics’ novel oral antibiotic Zoliflodacin (ETX0914).
He received a bachelor’s degree in chemistry from the University of California, Berkeley and a doctorate in synthetic organic chemistry from MIT.
Marc Navre is a biopharmaceutical veteran with over 25 years of experience managing small-molecule and biologics discovery teams in small biotechnology and large pharmaceutical companies. He has extensive experience in the integration of new technologies and platform concepts into successful discovery programs leading to investigational new drug studies and approval, including Nesina, Tenapanor, and Marzeptacog alfa. In the field of antibiotics, Navre led the antibacterial program at Affymax Inc. that worked with the Glaxo Wellcome team in Verona, Italy. More recently, he served as consulting senior vice president of research at Achaogen Inc. after its initial public offering in 2014. Navre has also served as drug discovery and informatics consultant to Collaborative Drug Discovery Inc. since 2012.
Navre received a bachelor’s degree in chemistry from the Polytechnic Institute of New York and his doctorate in biochemistry from the University of California, Berkeley and completed postdoctoral training at Stanford University.
With over 20 years in the pharmaceutical and biotechnology industries, Quinn has extensive drug discovery and development experience, focusing on the discovery of novel antibacterials and antifungals. As an independent consultant, she sits on scientific advisory boards and evaluates drug discovery programs and strategic alliances. Her research expertise covers many aspects of drug discovery, from microbiology to identifying promising candidates from screens. Quinn led drug discovery teams at Cubist Pharmaceuticals Inc., Pharmacia & Upjohn Co. Inc., and Pfizer Inc., where she rose to director of antibacterial pharmacology. While Quinn’s passion is for drug discovery and development, she has also led business efforts, culminating in her tenure as CEO of ImmuVen Inc., a T-cell receptor-based technology company that was bought by a large global pharmaceutical company. An active reviewer for NIH study sections for over 10 years, Quinn also reviews manuscripts for many journals such as Antimicrobial Agents and Chemotherapy, PLOS ONE, and Journal of Bacteriology, and served four terms on the editorial board of Applied and Environmental Microbiology. She is an inventor on 42 issued patents.
Quinn graduated magna cum laude from the University of Minnesota with a bachelor’s degree in microbiology and biochemistry, received a doctorate in biochemistry from the University of Illinois, and did postdoctoral research in molecular immunology at Oxford University.
Aileen Rubio was most recently the head of biology for Spero Therapeutics Inc., whose mission is to develop new treatments for bacterial infections. During her three and a half years there, she built and led internal microbiology and in vivo pharmacology efforts, managed external collaborations and led several discovery projects. Prior to Spero, she spent over nine years at Cubist Pharmaceuticals Inc., where she worked on multiple antibacterial discovery projects, managed the in house microbiology team, and provided support for business development activities. She has also collaborated with several key opinion leaders to investigate the mechanism of action and resistance to the antibiotic Cubicin (daptomycin) in Staphylococcus aureus. She remains an active member of the community by sitting on NIH study sections, as reviewer for Antimicrobial Agents and Chemotherapy (AAC) and ACS Infectious Diseases and through her involvement with the Pew Charitable Trusts’ efforts over several years.
Rubio received bachelor’s degrees in microbiology and chemistry from the University of Illinois, Urbana-Champaign and a doctorate in bacteriology from the University of Wisconsin, Madison. She completed postdoctoral research at the University of California, San Diego.
Brad Sherborne is a computational chemist who has led efforts in modeling, cheminformatics, and bioinformatics.
He heads the computational chemistry efforts at Merck & Co. Inc. in Kenilworth, New Jersey, where he maintains a strong interest in the relationship between chemistry and pharmacology.
Previously, he spent 10 years developing skills and experience at F. Hoffmann-La Roche.
Sherborne received his doctorate from the University of East Anglia, England.
Lynn Silver joined the Merck Research Laboratories in 1982. While at Merck, she did research and supervised microbiologists involved in discovery efforts for new antibacterials in natural products and chemical collections, supporting chemical synthetic projects on improved antibacterials, and preclinical evaluation of antibacterial drug candidates. Her studies included work on the mode of action and mechanism of resistance of inhibitors of lipid A synthesis, DNA, cell wall, protein, and fatty acid synthesis, as well as modification and optimization of macrolides, glycopeptides, and beta-lactams to overcome resistance and toxicity. She has been an independent consultant in antibacterial discovery since 2004.
Silver received a bachelor’s degree in biology from Brandeis University and a doctorate from Tufts University’s department of molecular biology and microbiology. She held two postdoctoral positions in DNA replication.
David Swinney has a long interest in understanding how to discover better drugs more efficiently. Swinney has over 25 years of preclinical drug discovery experience (at the Institute for Rare and Neglected Diseases Drug Discovery, or iRND3, F. Hoffmann-La Roche, Syntex Corp.) working to identify promising strategies, leads, clinical candidates and effective mechanisms of drug action that address unmet medical needs across many therapeutic areas, including infectious diseases and inflammatory diseases. He has expertise in drug discovery, discovery strategies, assay development and screening, enzymology, pharmacology and binding kinetics. He currently distributes his time between the 501(c)(3) organization iRRND3, which he helped found, and other projects that focus on aspects of drug action and discovery.
He holds a doctorate in medicinal chemistry from the University of Washington, Seattle.
Andrew Tomaras is vice president and director of microbiology at BacterioScan Inc. His dissertation work focused on the development of novel methods to genetically manipulate the Gram-negative pathogen Acinetobacter baumannii, and he conducted his postdoctoral studies at the University of Colorado Health Sciences Center. The latter experience led to his recruitment to the antibacterials research unit at Pfizer Global Research & Development, where his roles included minimizing the risk of antibiotic resistance development for preclinical projects portfoliowide and establishing new screening modalities to identify the next generation of antibiotic candidates. After Pfizer’s withdrawal from the small-molecule anti-infective therapeutic area, he was invited to help the company establish a new group focusing on the discovery of monoclonal antibodies that could serve as novel antibiotics.
Tomaras received his bachelor’s and doctoral degrees from Miami University, Oxford, Ohio.
Helen Zgurskaya is a professor in the department of chemistry and biochemistry at the University of Oklahoma, Norman. She has held research appointments at the Max Planck Institute of Molecular Genetics in Berlin, Stanford University Medical School, and the University of California, Berkeley. She has published more than 50 peer-reviewed articles on the mechanism of multidrug efflux and antibiotic resistance. Her current research focuses on mechanisms of bacterial multidrug efflux pumps and the permeability of Gram-negative bacteria.
Zgurskaya received a master’s degree in microbiology from Dnepropetrovsk State University, Ukraine, and a doctorate in microbiology from the Russian Academy of Sciences.
Johannes Zuegg is the program coordinator for the Community for Open Antimicrobial Drug Discovery (CO-ADD) at the Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia. CO-ADD advances public knowledge on antimicrobials by providing screening and antimicrobial development to academic institutions around the world. He is responsible for the logistics of compound screening, data and collaborator management, and analysis and modeling of the antimicrobial screening results. Previously, Zuegg helped to establish the Centre for Drug Discovery and Design at the University of Queensland, a central facility for drug development and lead optimization, where he managed several anti-cancer and antibacterial research projects. Before that, Zuegg spent eight years as head of information technology and molecular modeling at Alchemia Pty Ltd., a small biotech company in Brisbane, helping in the design and production of a large structural diversity screening library based on carbohydrate scaffolds.
Zuegg received master’s and doctoral degrees in chemistry and molecular modeling from the Technical University of Graz, Austria, before moving to Australia for a postdoctoral position at John Curtin School of Medical Research at the Australian National University.
Note: The development of SPARK has also benefited from the expertise of Joshua Bittker in his role as director of lead discovery at the Broad Institute and Ruben Tommasi, chief scientific officer at Entasis Therapeutics.