Cystic Fibrosis: From Gene Discovery to Basic Biology to Precision Medicines

Francis S. Collins, M.D., Ph.D. was appointed the 16th Director of the National Institutes of Health (NIH) by President Barack Obama and confirmed by the Senate. He was sworn in on August 17, 2009. On June 6, 2017, President Donald Trump announced his selection of Dr. Collins to continue to serve as the NIH Director. In this role, Dr. Collins oversees the work of the largest supporter of biomedical research in the world, spanning the spectrum from basic to clinical research.

Dr. Collins is a physician-geneticist noted for his landmark discoveries of disease genes and his leadership of the international Human Genome Project, which culminated in April 2003 with the completion of a finished sequence of the human DNA instruction book. He served as director of the National Human Genome Research Institute at NIH from 1993-2008.

Before coming to NIH, Dr. Collins was a Howard Hughes Medical Institute investigator at the University of Michigan. He is an elected member of the National Academy of Medicine and the National Academy of Sciences, was awarded the Presidential Medal of Freedom in November 2007, and received the National Medal of Science in 2009.

Dr. Negulescu received both his B.S. and Ph.D. from U.C. Berkeley in Physiology and carried out post-doctoral work at U.C. Berkeley and U.C. Irvine in the areas of epithelial biology, biophysics and immunology.

Following post-doctoral work, Paul joined Aurora Biosciences, a San Diego Company whose founders included Roger Tsien, in 1996. Paul joined as one of the first employees and grew with the Company to become Senior Vice President of Discovery Biology.  Paul began working on cystic fibrosis while at Aurora and played an important role in establishing the foundation of a more than 20-year journey in CF research and drug discovery.

When Vertex acquired Aurora in 2001, Paul was responsible for integrating Aurora’s research into Vertex, including transitioning the CF Program to Vertex.  Since 2003, Paul has led the Vertex San Diego research site. During that time the San Diego team has discovered over 10 novel compounds, including the first CFTR modulators to enter clinical development. Three of these compounds, ivacaftor, lumacaftor and tezacaftor are the only approved medicines to treat the underlying cause of cystic fibrosis.  Additional compounds are currently in clinical development that could treat up to 90% of people with CF.

Bonnie Ramsey MD is Professor and Vice Chair for Research in the Department of Pediatrics and holds the Endowed Chair in Cystic Fibrosis at the University of Washington School of Medicine.  She is also the Director of the Center for Clinical and Translational Research (CCTR) at Seattle Children’s Research Institute and is the co-PI of the University of Washington Institute of Translational Health Sciences (ITHS) supported by the NCATS Clinical Translational Science Award (CTSA). She is an elected member of the National Academy of Medicine

Dr. Ramsey received her BA from Stanford University in 1972 and her MD from Harvard Medical School in 1976. After pediatric residency training at Boston Children’s Hospital, she moved Seattle Children’s in 1978 first as a resident and fellow and then became an attending physician in 1980. Her career has focused on clinical care and research in the field of Cystic Fibrosis (CF). She is internationally recognized for her work in developing new therapies for patients with CF. She is also interested in the ethics of pediatric clinical research and has served on two Institute of Medicine committees focused on this topic.

Her primary research interest has been better understanding Pseudomonas aeruginosa (Pa) infections in the CF airway in order to develop better therapies. Over the past 2 decades she has led a large natural history of early Pa infection in young children with CF, the Early Pa Infection Control(EPIC) study, creating one of the world’s largest data and microbiological specimen collection in this population. Since the 1990’s, she has studied the role of inhaled antibiotics in treatment of Pa infections including the development of inhaled tobramycin ( TOBI®) initially for patients with established infections and more recently for eradication of early infections.

For nearly the past two decades, Bonnie directed the Coordinating Center for the Cystic Fibrosis Foundation Therapeutics (CFFT) Development Network (TDN), a national clinical trials network that has successfully conducted therapeutic trials assisting in the development of novel treatments for patients with this disorder. Several of the drugs have reached FDA approval, significantly impacting the lives of patients with CF. She now serves as a Senior Consultant to the TDN.

Professor Lap-Chee Tsui is the Founding President of the Academy of Sciences of Hong Kong, President of the Victor and William Fung Foundation, Director of Qiushi Academy for Advanced Studies and Master of the Residential College of International Campus, Zhejiang University.  He is also the University of Toronto’s Emeritus University Professor.

He is the immediate-past Vice Chancellor of The University of Hong Kong, prior to which, he was Geneticist-in-Chief at the Hospital for Sick Children in Toronto and University Professor at University of Toronto, Canada
He received his Bachelor and Master degrees from the Chinese University of Hong Kong and his PhD from University of Pittsburgh.  He is world renowned for his research work in human genetics and genomics, including the identification of the gene for Cystic Fibrosis, which is an important piece of work in defining the basic defect of the disorder and in human genetic disease research as a whole. His other contributions include the cloning and characterization of mammalian crystallin genes and a comprehensive mapping and characterization of human chromosome 7.

Professor Tsui has over 300 peer-reviewed scientific publications and 65 invited book chapters.  He is the recipient of many national/international prizes, and is a Fellow of Royal Society of Canada, Royal Society of London and Academia Sinica.  He is a Associate Member of the National Academy of Sciences USA, a Foreign Member of Chinese Academy of Sciences, and is a Canadian Medical Hall of Fame Laureate.  His other awards include 15 honorary doctoral degrees, the Orders of Canada and Ontario, and the Grand Bauhinia Medal and Gold Bauhinia Star, and Justice of the Peace from Hong Kong.

Dr. Welsh received an MD and completed an internal medicine residency at the University of Iowa.  He trained in pulmonary medicine and research at the University of California, San Francisco and the University of Texas, Houston.  He then joined the University of Iowa as an Assistant Professor, where his clinical activies focused on pulmonary diseases.  He is currently the Roy J. Carver Professor of Internal Medicine and Molecular Physiology and Biophysics.  He directs the Pappajohn Biomedical Institute and the Cystic Fibrosis Research Center.  He is an Investigator of the Howard Hughes Medical Institute.

Dr. Welsh served as President of the American Society for Clinical Investigation and as President of the Association of American Physicians.  He has been elected to the National Academy of Medicine, the American Academy of Arts and Sciences, and the National Academy of Sciences.

He has received many awards including the Carver College of Medicine Distinguished Mentor Award, the Cystic Fibrosis Foundation Paul di Sant'Agnese Distinguished Scientific Achievement Award, the American Thoracic Society J. Burns Amberson Award, the Doris F. Tulcin Cystic Fibrosis Research Award, the American Physiological Society Walter B. Cannon Award, and the Indiana University Steven C. Beering Award.