A team of UCSF scientists has launched a high-tech search for new causes of chronic diseases, such as asthma, autoimmune disease and some degenerative disorders.
Employing a DNA microarray tool developed at UCSF, the researchers will look for previously unknown viruses in clinical specimens from people with these chronic diseases. The team will also use the DNA probe to determine if known viruses cause diseases that have been attributed to other, noninfectious causes.
Recently, scientists have recognized that many chronic diseases once thought to have genetic, metabolic or other causes are, in fact, triggered by viral infections. Peptic ulcer disease, Lyme arthritis and Kaposi's sarcoma all have now been shown to be precipitated by infection.
The new UCSF study is propelled by a genomics-based tool that allows scientists to quickly and with great precision identify viruses. This technique, developed by Joe DeRisi, PhD, UCSF assistant professor of biochemistry, and postdoctoral fellow David Wang, PhD, helped confirm the identify of the SARS virus last March.
The microarray tool bears sequences of all available human, animal, insect, plant, fungal and bacterial viruses, and identifies a sample virus by the similarity of its DNA to sequences of all the others. The technique can not only detect known viruses, but also novel members of known virus families, and even novel classes of agents that share only limited stretches of DNA with known viruses.
The five-year UCSF study is called Genomics-based Approaches to New Pathogen Discovery in Chronic Human Diseases. It is funded by a $1.9 million award from the Doris Duke Charitable Foundation that was designed to promote applications of high-technology to clinical investigation by teams of basic and clinical investigators.
The UCSF team is headed by Don Ganem, MD, professor microbiology and medicine and a nationally known virologist, and includes DeRisi and Homer Boushey, MD, professor of medicine and a widely recognized expert on asthma and other pulmonary diseases.
Microarrayer developed by Joe DeRisi’s lab.
The initial focus will be on chronic inflammatory lung and liver disorders with unknown causes. Candidate pathogens identified by the genomics technology will then be targeted for further study, including cloning the viral genomes and development of diagnostic tests. These will then be used to support a second round of clinical investigation to explore the epidemiology of infection in the human population and to determine the role of the candidate virus in the disease.
"What’s particularly exciting about this project is the fact that, unlike most forms of research, this work can only be done as an integrated team – no one group possesses all the skills needed to do this individually," Ganem says. "At each stage of the process, there is interaction between clinicians, virologists and genomicists, and each feeds off the other. Even though we each inhabit what are in many ways parallel universes, when these come into alignment -- however briefly -- the synergies are tremendous.”
The UCSF project is one of six to receive grants in the Doris Duke Foundation's new Clinical Interfaces program, intended to catalyze activity at the interface of clinical, population and basic sciences through support of cross-disciplinary research. Only the UCSF project was selected to receive a full, five-year grant from the Foundation.
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