Congratulations!
the Two 2010 $20,000 MAVRC Pilot Award Winners!
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"Ribonuclease L, RIG-I, Interferon and Immunity to Hepatitis C Virus"
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David J. Barton, Ph.D. (See BIO)
University of Colorado School of Medicine
Associate Professor of Microbiology
Phone: (303) 724-4215
david.barton@ucdenver.edu
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Hugo Rosen, M.D. (See BIO)
University of Colorado School of Medicine
Waterman Professor of Medicine and Immunology
Head, Division of Gastroenterology & Hepatology
Phone: (303) 724-1858
hugo.rosen@ucdenver.edu
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Jay R. Hesselberth, Ph.D. (See BIO)
University of Colorado School of Medicine
Assistant Professor, BioChemistry and Molecular Genetics
Phone: (303) 724-5384
jay.hesselberth@ucdenver.edu |
The Barton, Hesselberth and Rosen labs are working collaboratively to develop new methods that will detect and quantify the antiviral activity of ribonuclease L (RNase L) in liver biopsies from hepatitis C virus (HCV)-infected patients.
Interferon is commonly used to treat patients infected with HCV. Some strains of HCV are more resistant to interferon therapy than others; however, the molecular basis for interferon sensitivity and resistance in patients remains largely unexplained. RNase L, an antiviral host enzyme produced in interferon-treated cells, is predicted to inhibit HCV replication and to affect the outcomes of interferon therapy; however, no one has evidence to establish whether RNase L inhibits HCV in the liver of patients.
The Barton lab and collaborators have used biochemical experiments, tissue culture studies, animal models and bioinformatic approaches to characterize the antiviral activity of RNase L as it relates to HCV infections. The goal of the current project funded by MAVRC is to use liver biopsies from HCV-infected patients to test whether RNase L cleaves HCV RNA naturally in the liver of patients, as predicted.
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"Phenotyping the spectrum of latent tuberculosis infection through host expression profiling: The Expression in Pneumonia and Tuberculosis (ePAT) study"
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Randall R. Reves, M.D./M.Sc. (See BIO at Denver Health)
Denver Health Medical Center
Professor, Infectious Diseases
Phone: (303) 602-7257
randall.reves@dhha.org |
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Nicholas Walter, M.D., M.S.
University of Colorado Denver
Fellow, Pulmonary Sciences and Critical Care Medicine
Phone: (303) 724-4075
nicholas.walter@ucdenver.edu |
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Michael Strong, Ph.D. (See BIO)
National Jewish Health, Denver
Assistant Professor, Center for Genes, Environment and Health
Phone: (303) 270-2782
stongm@njhealth.org
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Charles Daley, M.D. (See BIO)
National Jewish Health, Denver
Chief, Mycobacterial and Respiratory Infections
Phone: (303) 398-1667
daleyc@njhealth.org |
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Mark Geraci, M.D. (See BIO)
University of Colorado Denver
Professor of Medicine, Pulmonary Sciences and Critical Care Medicine
Phone: (303) 724-6040
mark.geraci@ucdenver.edu |
Tuberculosis (TB) is an on-going public health crisis, causing 1.6 million deaths worldwide each year. It is estimated that approximately one-third of the world's population has latent TB infection (LTBI). However, even without treatment, fewer than 10% of latently infected immunocompetent persons develop TB over the course of a lifetime. Identifying the persons with LTBI who are most likely to progress to TB is a key public health priority but currently available tests for LTBI cannot risk-stratify among patients with latent infection.
Expression profiling -- the analysis of patterns of RNA expression in human clinical samples -- is a novel and potentially powerful means of identifying the subgroup of persons with LTBI who are at highest risk for developing TB. Whole-genome micro-array quantifies an individual's expression of approximately 28,000 RNA transcripts, providing a "biological snapshot" of ongoing transcriptional adaptation to physiologic stressors. We seek to identify host expression profiles in peripheral blood that distinguish patients with TB and LTBI from well controls and from patients with non-TB pneumonia.
ePAT is a longitudinal study of host gene expression among patients at Denver Health Medical Center with TB, LTBI, community acquired pneumonia and no infection. Through a new collaboration among investigators at Denver Health, National Jewish Health and the University of Colorado Denver, we aim to identify TB and LTBI-specific host expression profiles and to characterize the change in these profiles during the course of therapy.