Chronic viral infections are major causes of chronic inflammation and cancer. A well characterized example is virus-induced liver disease and hepatocellular carcinoma, the second leading cause of death world-wide. Using virus-induced liver disease and cancer as a model, we aim to develop sophisticated computational tools to investigate the host cell reprogramming induced by viruses during cancerogenesis. Leveraging and enhancing advanced computational approaches, we will develop an integrative genomic framework to identify the regulatory modules driving transcriptional and proteomic reprogramming associated with persistent viral infection and carcinogenesis. More specifically, we will develop a toolbox that allows for inferring regulatory mechanisms from time course data derived from different viral infections associated with similar disease biology and multiple functional genomics levels in an integrated manner. We hypothesize that the computational toolbox developed within this program will contribute to understand viral carcinogenesis and identify novel strategies for cancer prevention.

Public Health Relevance

The goal of this project is to develop an integrative genomic framework that allows for identifying the cell circuits driving transcriptional and proteome reprogramming associated with persistent viral infection and carcinogenesis, thus developing a powerful toolbox for application in pathogenesis of hepatocellular carcinoma and other cancers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA209940-02
Application #
9483712
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Abrams, Natalie
Project Start
2017-05-12
Project End
2019-04-30
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
Verrier, Eloi R; Yim, Seung-Ae; Heydmann, Laura et al. (2018) Hepatitis B Virus Evasion From Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase Sensing in Human Hepatocytes. Hepatology 68:1695-1709
Ligat, Gaetan; Schuster, Catherine; Baumert, Thomas F (2018) HBV core variants, liver fibrosis and hepatocellular carcinoma. Hepatology :
Champion, Magali; Brennan, Kevin; Croonenborghs, Tom et al. (2018) Module Analysis Captures Pancancer Genetically and Epigenetically Deregulated Cancer Driver Genes for Smoking and Antiviral Response. EBioMedicine 27:156-166
Foung, Steven K H; Baumert, Thomas F (2018) Editorial: Current Progress and Challenges in the Development of a B Cell Based Hepatitis C Virus Vaccine. Front Immunol 9:2577
Virzì, Alessia; Roca Suarez, Armando Andres; Baumert, Thomas F et al. (2018) Oncogenic Signaling Induced by HCV Infection. Viruses 10:
Baumert, Thomas F; Berg, Thomas; Lim, Joseph K et al. (2018) Status of Direct-acting Antiviral Therapy for HCV Infection and Remaining Challenges. Gastroenterology :