Early Infectious Disease Diagnosis Using Genomics

A key pillar and unmet need in the defense against threats to health is the ability to recognize the etiological factor(s) and predict the course of disease, at early points in the timeline of the process. This ability would enable early intervention in the disease process when there is the greatest likelihood of benefit, as well as triaging of hosts, based on individual need. Genomic tools and approaches have enabled a more detailed description of host-microbe encounters, and shed light on fundamentally important processes, including the cellular responses associated with infection. Genome-wide transcript-abundance profiles, like other comprehensive molecular readouts of host physiological state, provide a detailed blueprint of the host-pathogen dialogue during microbial disease. Studies of cancer based on genome-wide transcript-abundance profiles have led to novel signatures that predict disease outcome and serve as useful clinical classifiers. The highly dynamic and compartmentalized aspects of the host response to pathogens complicate efforts to identify predictive signatures for infectious diseases. Yet, studies of systemic infectious diseases so far suggest the possibility of successfully discriminating between different types (classes) of infection and predicting clinical outcome. In addition, host gene expression analysis could lead to the identification of early signatures associated with a protective immune response, both to natural infection and to vaccination. Early explorations in some of these areas indicate the potential feasibility of this approach but also point to important unmet challenges.

David Relman is associate professor of medicine, and of microbiology and immunology at Stanford University. He is also chief, infectious diseases section, at the VA Palo Alto Health Care System in Palo Alto, California.

A native of Boston, Massachusetts, Relman holds an SB degree from the Massachusetts Institute of Technology and received his MD degree, magna cum laude, from Harvard Medical School in 1982. Following postdoctoral clinical training at Massachusetts General Hospital in internal medicine and in infectious diseases, Relman served as a postdoctoral research fellow in microbiology at Stanford University in the laboratory of Stanley Falkow from 1986 until 1992. He joined the Stanford University faculty in 1992 and was appointed associate professor (with tenure) in 2001. His research is directed towards the characterization of the human indigenous microbial communities of the mouth and gut, with emphasis on understanding variation in diversity, succession, the effects of disturbance, and the role of these communities in oral and intestinal disease.

Experimental approaches include molecular phylogenetics, ecological statistics, single cell genomics, and community-wide metagenomics. A second area of research concerns the classification structure of humans and non-human primates with systemic infectious diseases, based on patterns of genome-wide gene transcript abundance in blood and other tissues. The goals of this work are to recognize classes of pathogen and predict clinical outcome at early time points in the disease process, as well as gain further insights into virulence (e.g., of variola and monkeypox viruses). Past achievements include the description of a novel approach for identifying previously-unknown pathogens (selected as one of the 50 most important papers of the last century by the American Society for Microbiology), the identification of a number of new human microbial pathogens, including the agent of Whipple's disease, and the most extensive descriptions to date of the human indigenous microbial community. See http://relman.stanford.edu. Relman received the Squibb Award from the Infectious Diseases Society of America (2001), the Senior Scholar Award in Global Infectious Diseases from the Ellison Medical Foundation (2002), and is a recipient of an NIH Director's Pioneer Award (2006). He is a member of the American Society for Clinical Investigation and was named a Fellow of the American Academy of Microbiology in 2003.

Relman currently serves on the Board of Scientific Counselors of the National Institute of Dental and Craniofacial Research and was a member of the Board of Directors of the Infectious Diseases Society of America (2003-2006), and co-chair of the National Academy of Sciences' Committee on Advances in Technology and the Prevention of Their Application to Next Generation Biowarfare (2004-2006). He is a member of the National Science Advisory Board for Biosecurity, the Institute of Medicine's Forum on Microbial Threats, and advises several U.S. Government departments and agencies on matters related to microbial pathogen detection and future biological threats.