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Interferon's Involvement in Viral Infection and Cancer

Irene Munk Pederson

Appointment Period: 2006-2007 / Grant Year: [22]

Irene MunK PedersonViruses represent one of the main factors that cause normal cells to proliferate and to become malignant; up to 15% of all human cancers are associated with virus infections, and several viruses have been recognized as a causal agent of specific types of cancer. One good example is the link between Hepatitis C Virus (HCV) and the development of liver cancer. Approximately 4 million persons in the United States and probably more than 100 million people worldwide are infected with HCV. 70% to 80% of infected persons become chronic carriers, with a significant morbidity and mortality caused by cirrhosis, end-stage liver disease, and liver cancer. Despite the fact that interferons (IFNs) are the treatment of choice for HCV, little is known about how IFNs mediate their antiviral effects. Therefore, I will study the effects of IFN in regards to clearage of HCV infection and tumorigenesis, and believe that our findings are likely to be of significant clinical relevance.

Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, David M. Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature. (2007) 449:919-22. PMID: 17943132; PMCID: PMC2748825.

Pedersen I, David M. MicroRNAs in the immune response. Cytokine. (2008) 43:391-4. PMID: 18701320.

Pedersen IM, Otero D, Kao E, Miletic AV, Hother C, Ralfkiaer E, Rickert RC, Gronbaek K, David M. Onco-miR-155 targets SHIP1 to promote TNFalpha-dependent growth of B cell lymphomas. EMBO Mol Med. (2009) 1:288-95. PMID: 19890474; PMCID: PMC2771872.

Miletic AV, Anzelon-Mills AN, Mills DM, Omori SA, Pedersen IM, Shin DM, Ravetch JV, Bolland S, Morse HC 3rd, Rickert RC. Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases. J Exp Med. (2010) 207:2407-20. PMID: 20956547; PMCID: PMC2964567.

Moro H, Otero DC, Tanabe Y, David M. T cell-intrinsic and extrinsic contributions of the IFNAR/STAT1-axis to thymocyte survival. PLoS One.2011;6(9):e24972. Epub 2011 Sep 20. PubMed PMID: 21949815; PubMed Central PMCID: PMC3176796.