Colorectal cancer develops in what is probably the most complex environment in the human body, a place where human cells cohabitate with a colony of approximately 10 trillion bacteria, most of which are unknown.
What happens when you bring a medical doctor, an immunologist and a marine biologist together to take medicine from the lab to the patients? Great things. University of Arizona researchers have been awarded a $200,000 two-year seed grant by theFlinn Foundation through its Promoting Translational Research in Precision Medicine grants program to find out how a virus that flies under the radar of the body's immune defense may influence health, disease and even behavior. The goal of the seed grant program is to foster collaborative efforts between physician-scientists and bench researchers in order to translate findings more rapidly to actual patient treatments. "Precision medicine" – also known as "personalized medicine" – is one of the strategic initiatives of the UA's Never Settle strategic plan, with considerable investments planned for new infrastructure and 50 new faculty hires over the next 10 years. Precision medicine aims at closing the gap that currently exists between scientific advances and clinical practice. The more researchers discover about the molecular mechanisms underlying diseases, the clearer it becomes that one treatment does not fit all. By integrating such knowledge with clinical data on individual patients, precision medicine entails tailoring treatments to individual cases and improving outcomes for the patients. The unique research team consists of UA associate professor of medicine Ken Knox, who specializes in pulmonary medicine and has a strong track record in clinical and translational research; UA associate professor of immunobiology, BIO5 Institute member and biomedical researcher Felicia Goodrum, who is an expert in viral persistence; and UA associate professor of ecology and evolutionary biology and BIO5 member Matthew Sullivan, an expert in viral metagenomics. The team will unravel which viruses make their homes in the lung without causing symptoms. Specifically, they will home in on one such virus, the cytomegalovirus, known as CMV, which belongs to the herpes virus family. The human body is home to a vast number of bacteria, viruses and fungi that collectively make up the human microbiome. Much of our microbiome does not cause disease, but rather is critically important to maintaining human health. Recent studies in humans document the enormous impact bacteria have on normal health (e.g., obesity), disease states (e.g., diabetes, gastrointestinal disorders), and even behavior. The role of viruses, by contrast, represents uncharted frontiers for study. Human CMV is one of eight human herpes viruses and infects 60-90 percent of the population worldwide and, like all herpes viruses, persists in the infected host indefinitely by way of a latent infection. CMV’s primary infection of healthy individuals is typically asymptomatic and, therefore, goes completely unnoticed. When CMV is reactivated from latency to an active state of replication, there are life-threatening disease risks in immunocompromised people, including transplant and cancer patients. CMV infection is also the leading cause of infectious disease-related birth defects, affecting 1 percent of live births in the United States. Persistent viruses represent emerging health threats that contribute to chronic inflammation, cellular stress and cancer risk. In addition, latent viral coexistence is just beginning to emerge in association with age-related pathologies, including atherosclerosis, immune senescence and frailty. Health costs of persistent viral infections, whether chronic or latent, can be significant. Knox, Goodrum and Sullivan will study CMV as a model of persistent viral infection upon which to base questions related to how to specifically prevent lung infections. Just as genetic makeup is different among individuals, so are their immunological reactions to invading viruses, which in turn influences how disease states manifest from individual to individual. By using advanced informatics to analyze metagenomic data sets from the study, the team will investigate correlations between the presence of human CMV and what scientists call the background virome: the "zoo" of viral populations present in a given individual. “Translational research – moving discoveries from the lab to patient care – is a crucial element of precision, or personalized, medicine as well Arizona’s bioscience strategy,” said Jack B. Jewett, president and CEO of the Flinn Foundation, a philanthropic organization committed to improving the quality of life in Arizona to benefit future generations. “This exciting collaboration among Drs. Knox, Goodrum and Sullivan is an outstanding example of a potentially groundbreaking research project that could ultimately yield great benefits to human health.” “This study is extremely important and timely, as known and yet-to-be discovered viruses are undoubtedly influencing human health and contributing to disease states," said Janko Nikolich-Zugich, Elizabeth Bowman Professor in Medical Research and head of the UA Department of Immunobiology. Fernando Martinez, MD, UA Regents’ Professor of Pediatrics and director of both the Arizona Respiratory Center and the BIO5 Institute, agreed, adding, "Defining the viruses present in the human lung will be an important step in expanding our knowledge base of the pulmonary virome. In addition, techniques used to identify viruses hold promise for rapid diagnostics and treatments." Other members of the study team at the UA include PhD candidates Katie Caviness and Ann Gregory, senior research scientist Bonnie Poulos, Heidi Erickson, and Lance Nesbit. The current study also will examine viral reservoirs in the context of lung transplants and thus is likely to have broad implications for our understanding of pulmonary immunity and rejection.
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