Projects & Collaborations 11 foundShow per page10 10 20 50 Host-virus interactions in hepatitis B virus infection Research Project | 1 Project MembersNo Description available A new high-resolution LC-MS platform for high precision and throughput quantitative biology to support life science research at the Biozentrum of the University of Basel Research Project | 6 Project MembersLife science research is performed at many institutes and clinics at the University of Basel and encompasses areas from clinical studies to in-vitro studies with cellular systems or pathogens. Omics technologies are increasingly applied in these projects in order to gain detailed insights into biomolecular processes involved during homeostasis, regulation and perturbation of biological systems. Although genomics provides useful information on the genetic composition of a cell or organism, it is often insufficient to explain the observed biological phenotypes. These questions need to be answered by studying the protein complement (proteome) and cellular signalling by analysing post-translational modifications like phosphorylation (phosphoproteome). As outlined in this proposal, the different projects aim at a better understanding of complex processes involved in initiation and progression of diseases, including bacterial vaccination, malaria, cancer and muscle diseases, using proteomics data. Specifically, the following five projects of the proposal are described: Project 1 attempts to establish molecular mechanisms mediating responsiveness to targeted cancer therapy by generating proteome and phosphoproteome maps from serial biopsies of hepatocellular carcinoma patients (HCC) before and during drug treatment. We then take an 'multi-omics' approach to find molecular patterns predictive for treatment success. Project 2 focuses on the discovery of evasive signaling pathways in hepatocellular carcinoma (HCC) by quantitative proteome and phosphoproteome comparisons of patient-derived tumor organoids after Sorafenib treatment at different time points. Project 3 employs data-independent proteomics to define cellular protein concentrations of Staphylococcus aureus proteins in patient abscesses and lung secretions. We will then use a reverse translational approach to find key components for urgently needed protective vaccines. Projects 4 intends to gain novel important insights into the complex regulation of the biological program of muscle adaptation to exercise by integrating proteome, signaling and protein-protein interaction data obtained from LC-MS analyses. Project 5 will employ targeted proteomics to identify components of the molecular machinery that regulates singular gene choice, an intriguing transcriptional control mechanism that facilitates antigenic variation and immune evasion of malaria parasites. The proposed projects pose extremely challenging demands on protein sample analysis in terms of sensitivity, precision and throughput. Like in all clinical studies, due to the high interpatient variability, high sample numbers are required to achieve sufficient statistical power for confident target discovery and validation. Moreover, many proteins and modifications of interest are low abundant and very challenging to quantify consistently with high precision across large sample batches. After extensive evaluation, we found the Q Exactive HF-X mass spectrometer to be the only instrument on the market to have sufficient speed and sensitivity to meet these high analytical requirements. In particular, its compatibility with data-independent workflows and new on-the-fly acquisition software allows unprecedented proteome coverage in discovery and the highest sensitivity and throughput for targeted MS experiments. We are convinced that the new Q Exactive HF-X is the instrument of choice to fullfil the requirements of the projects listed above, and many more to come in the future. Interferon Regulated Immune Responses in Viral Hepatitis Research Project | 1 Project MembersInterferons (IFNs) are central regulators of the host immune response to viral hepatitis. T-cell derived IFNγ is a major antiviral effector controlling both hepatitis C virus and hepatitis B virus infection. IFNα is being used since 30 years for treatment of chronic hepatitis B (CHB) and C (CHC). More recently, IFNλ4 has been identified as a key regulator of the immune response to HCV. The IFNλ4 gene exists in two major allelic variants. The ancestral allele encodes a fully functional IFNλ4. An insertion mutation (changing a G to a TT) disrupts the open reading frame of IFNλ4. Genome wide association studies discovered a highly significant association of the TT allele with spontaneous clearance of HCV. It is presently unclear why IFNλ4 is a liability in case of an HCV infection. We hypothesize that IFNλ4 negatively regulates the cellular immune response to HCV. In this application, we propose three subprojects that investigate different aspects of the IFNλ system in viral hepatitis, with a focus on the specific role of IFNλ4 in the host response to HCV. In subproject 1 we will study the biochemistry, physiology, tissue distribution and natural regulation of IFNλ4. In subproject 2 we will study the regulation of the IFNλ receptor. Contrary to the ubiquitous expression of the IFNα receptor in all cell types and organs, IFNλ receptor expression is restricted mainly to epithelial cells. However, its expression can be induced in other cell types such as hepatocytes or dendritic cells. A better understanding of the regulation of IFNλ receptor expression should provide important insights into the biological function of the IFNλ system. In subproject 3 we plan to identify the IFNλ responsive immune cells and to elucidate the cell-cell network and the cytokines involved that regulate the immune response to HCV. Simultaneously with these subprojects focused on the IFNλ system, we plan to develop human biopsy derived liver organoids as an experimental model to study inter-individual differences in cellular responses to HCV and HBV in subproject 4 . Current in vitro models for HCV and HBV are based on few hepatoma derived cell lines and primary human hepatocytes. Both systems have major limitations. Human liver biopsy derived organoids might overcome some of these limitations. Because they can be derived from individual patients they have a unique potential to enable the study of inter-individual differences in cellular responses to hepatitis viruses. MERiC Research Project | 4 Project MembersCancer is a major health problem due to the failure of current therapies to effectively eradicate the disease. Extensive research over decades has led to the development of therapies that target cancer-specific signaling pathways. However, tumors escape such therapies by activating compensatory signaling pathways, a process referred to as 'evasive resistance'. The identities of the alternative signaling pathways and functional interconnections that underlie evasive resistance remain widely unknown. Elucidating mechanisms of evasive resistance is currently the major challenge in cancer research. We will integrate cutting-edge clinical, molecular, and computational sciences in a pioneering project to understand the signaling defects that enable tumors to evade therapy. With its synergistic, interdisciplinary approach, the proposed project is, to our knowledge, unique in Europe and possibly worldwide. Within the framework of rigorously designed clinical studies, a clinician (PI: M. Heim) will provide basic research scientists with hepatocellular carcinoma (HCC) tissue isolated before therapy, during treatment, or at the time of tumor progression. HCC is chosen as the focal cancer based on medical importance, accessibility to repeated sampling, and ethical considerations. The tumor tissue will be obtained by needle biopsy and immediately snap frozen to preserve in vivo tumor properties. The basic research scientists (PIs: G. Christofori and M. Hall) and a computational biologist (PI: N. Beerenwinkel) will apply high- and low-throughput experimental and computational methods to determine, characterize, and model the underlying signaling defects. Importantly, using longitudinal clinical samples in combination with mouse and cellular HCC model systems, we will define treatment-related changes in cell signaling that allow tumors to circumvent therapy. This process will be iterative such that changes in treatment strategies will again be monitored in the same patient or experimental model. Insights gained will (i) reveal molecular pathomechanisms in oncogenesis, (ii) identify novel drug targets and predictive biomarkers, and (iii) lead to the rational design of personalized medicine that ultimately benefits patients by increasing therapeutic effectiveness and reducing side effects and financial burden. In aggregate, this innovative, comprehensive endeavor will elucidate mechanisms of evasive resistance and will ultimately improve cancer diagnosis, treatment and clinical outcome. Role of Hepatitis C Virus (HCV) RNA-Dependent RNA Polymerase NS5B activity in HCV pathogenesis, persistence, and regulation of antiviral defense in humans Research Project | 1 Project MembersHepatitis C virus (HCV) is a positive-strand RNA virus infecting approximately 150 million persons worldwide. HCV infection can cause chronic liver disease and lead to liver cirrhosis and/or liver cancer. There is no vaccine for HCV, and current therapy has only limited efficiency and multiple side effects. HCV induces strong innate immune response within first days of infection, that includes production of type I IFN. This response leads to viral clearance in ~30% of patients, however, in other ~70% of cases infection becomes chronic. Mechanisms of HCV persistence and immune escape are poorly understood. For RNA viruses, it is believed that innate immune response is triggered solely by viral genome replication intermediates, such as double-stranded RNA (dsRNA) or 5'-triphosphate-containing (5'-ppp) RNA, generated by viral RNA-dependent RNA polymerases (RdRp). However, this is unlikely for HCV, as its replication takes place in hidden compartments, and viral RNA is, presumably, not exposed to innate immune sensors. It has been demonstrated recently that HCV RdRp (NS5B) can use host cell RNA as template and generate small dsRNA molecules that trigger IFN production in mouse livers and in cultured liver cells. We hypothesize, that this non-specific activity of HCV NS5B protein is the major activator of innate immunity in acute HCV infection in humans, and contributes to HCV persistence and immune regulation in chronic phase. The proposed study will aim at finding out how HCV NS5B activity and production of small dsRNA species affect the course and outcome of HCV infection. We will use human liver biopsies from infected patients, molecular biology and biochemistry techniques, next-generation sequencing and bioinformatics to characterize HCV-induced small dsRNA species and analyze their role in host-virus interactions in HCV infection. A thorough understanding of these interactions will facilitate the development of better therapies and a preventive vaccine. SX MERiC Mechanisms of Evasive Resistance in Cancer Research Project | 5 Project MembersMechanisms of Evasive Resistance in Cancer Cancer is a major health problem, but current cancer therapies fail to effectively eliminate the disease. The RTD Project MERIC now aims to find out how tumor cells change their signaling pathways to escape treatment. Extensive research over decades has led to the development of therapies that target cancer-specific signaling pathways. Tumors can however escape such therapies by activating compensatory signaling pathways, a process referred to as "evasive resistance". The identities of the alternative signaling pathways and the functional interconnections that underlie evasive resistance remain widely unknown. Elucidating their mechanisms is currently a major challenge in cancer research. Shedding light on the mechanism of evasive resistance To understand the changes in the signaling pathways that enable tumors to evade therapy, the scientists working on the RTD Project MERIC will integrate cutting-edge clinical, computational, and molecular approaches. With the help of rigorously designed clinical studies, the scientists will be able to work with diseased tissue isolated before therapy, during treatment, and at the time of tumor progression. The tissue, chosen based on medical importance, accessibility to repeated sampling, and ethical considerations, will come from hepatocellular carcinoma (HCC). The biomedical scientists and computational biologists in the team will apply high- and low-throughput experimental and computational methods to determine, characterize, and model the underlying signaling defects that allow tumors to circumvent therapy. Following cellular signaling changes of cancer cells over time This research process will be iterative, meaning that the researchers will monitor changes in treatment strategies several times in the same patient or experimental model. This way, they will be able to follow the individual changes in cell signaling of the respective tumors, and track the influence of the medication. Once the molecular pathomechanisms in oncogenesis are revealed, the interdisciplinary MERIC team plans to identify new drug targets and predictive biomarkers. In doing so, they hope to contribute to the rational design of personalized medicine approaches by increasing therapeutic efficacy and reducing side effects and the financial burden of treatment for the benefit of the patient. Innate Immune Responses to Hepatitis C Virus Infections Research Project | 1 Project MembersChronic hepatitis C (CHC) is a major cause of chronic liver disease. An important and striking feature of hepatitis C virus (HCV) is its tendency toward chronicity. In > 70% of infected individuals, HCV establishes a persistent infection over decades that may lead to cirrhosis and hepatocellular carcinoma. This high rate of persistence is linked to an ability of HCV to evade and antagonize the immune response of the host. Type I interferons (IFNs) are crucial and potent components of the early host response against virus infection and recombinant pegylated IFNα (pegIFNα) in combination with ribavirin is the current standard therapy for CHC. About half of the patients can be cured. In the current research grant application, we plan to address several key points of the innate immune response to hepatitis C virus infection. 1. Analysis of liver biopsies of HCV infected patients with a newly developed fluorescence in situ hybridization method (FISH). We will use a newly developed FISH method to visualize and quantify HCV RNA and mRNAs of IFNs and IFN stimulated genes in liver biopsies. 2. IFNα induced signaling in the human liver. The pharmacodynamic effects of pegylated IFNα will be studied in liver biopsies obtained at different time points during the week after the first injection of pegylated IFNα in patients with CHC . 3. The role of IFNλ in establishing and maintaining IFN stimulated gene expression in the liver of HCV infected patients. We plan to systematically study IFNλ and IFNλ receptor expression in liver biopsies of patients with chronic hepatitis C (and controls) and correlate the status of the IFNλ system with hepatic IFN stimulated gene expression. We will investigate the molecular mechanisms that links IL28B genotype with IFN stimulated gene expression and with non-response to pegIFN-α/ribavirin combination therapies. 4. Functional characterization of IFNα induced long non-coding RNAs (lncRNAs) We have identified hundreds of lncRNAs that are induced by IFNα. We plan to study if some of them have a role in negative regulation of genes by IFNα. Interferon Signaling and Innate Immunity in Chronic Viral Hepatitis Research Project | 1 Project MembersNo Description available Systems Biology of hepatic insulin resistance Research Project | 1 Project MembersNo Description available Hepatocarcinogenesis in chronic hepatitis C Research Project | 1 Project MembersNo Description available 12 12
Host-virus interactions in hepatitis B virus infection Research Project | 1 Project MembersNo Description available
A new high-resolution LC-MS platform for high precision and throughput quantitative biology to support life science research at the Biozentrum of the University of Basel Research Project | 6 Project MembersLife science research is performed at many institutes and clinics at the University of Basel and encompasses areas from clinical studies to in-vitro studies with cellular systems or pathogens. Omics technologies are increasingly applied in these projects in order to gain detailed insights into biomolecular processes involved during homeostasis, regulation and perturbation of biological systems. Although genomics provides useful information on the genetic composition of a cell or organism, it is often insufficient to explain the observed biological phenotypes. These questions need to be answered by studying the protein complement (proteome) and cellular signalling by analysing post-translational modifications like phosphorylation (phosphoproteome). As outlined in this proposal, the different projects aim at a better understanding of complex processes involved in initiation and progression of diseases, including bacterial vaccination, malaria, cancer and muscle diseases, using proteomics data. Specifically, the following five projects of the proposal are described: Project 1 attempts to establish molecular mechanisms mediating responsiveness to targeted cancer therapy by generating proteome and phosphoproteome maps from serial biopsies of hepatocellular carcinoma patients (HCC) before and during drug treatment. We then take an 'multi-omics' approach to find molecular patterns predictive for treatment success. Project 2 focuses on the discovery of evasive signaling pathways in hepatocellular carcinoma (HCC) by quantitative proteome and phosphoproteome comparisons of patient-derived tumor organoids after Sorafenib treatment at different time points. Project 3 employs data-independent proteomics to define cellular protein concentrations of Staphylococcus aureus proteins in patient abscesses and lung secretions. We will then use a reverse translational approach to find key components for urgently needed protective vaccines. Projects 4 intends to gain novel important insights into the complex regulation of the biological program of muscle adaptation to exercise by integrating proteome, signaling and protein-protein interaction data obtained from LC-MS analyses. Project 5 will employ targeted proteomics to identify components of the molecular machinery that regulates singular gene choice, an intriguing transcriptional control mechanism that facilitates antigenic variation and immune evasion of malaria parasites. The proposed projects pose extremely challenging demands on protein sample analysis in terms of sensitivity, precision and throughput. Like in all clinical studies, due to the high interpatient variability, high sample numbers are required to achieve sufficient statistical power for confident target discovery and validation. Moreover, many proteins and modifications of interest are low abundant and very challenging to quantify consistently with high precision across large sample batches. After extensive evaluation, we found the Q Exactive HF-X mass spectrometer to be the only instrument on the market to have sufficient speed and sensitivity to meet these high analytical requirements. In particular, its compatibility with data-independent workflows and new on-the-fly acquisition software allows unprecedented proteome coverage in discovery and the highest sensitivity and throughput for targeted MS experiments. We are convinced that the new Q Exactive HF-X is the instrument of choice to fullfil the requirements of the projects listed above, and many more to come in the future.
Interferon Regulated Immune Responses in Viral Hepatitis Research Project | 1 Project MembersInterferons (IFNs) are central regulators of the host immune response to viral hepatitis. T-cell derived IFNγ is a major antiviral effector controlling both hepatitis C virus and hepatitis B virus infection. IFNα is being used since 30 years for treatment of chronic hepatitis B (CHB) and C (CHC). More recently, IFNλ4 has been identified as a key regulator of the immune response to HCV. The IFNλ4 gene exists in two major allelic variants. The ancestral allele encodes a fully functional IFNλ4. An insertion mutation (changing a G to a TT) disrupts the open reading frame of IFNλ4. Genome wide association studies discovered a highly significant association of the TT allele with spontaneous clearance of HCV. It is presently unclear why IFNλ4 is a liability in case of an HCV infection. We hypothesize that IFNλ4 negatively regulates the cellular immune response to HCV. In this application, we propose three subprojects that investigate different aspects of the IFNλ system in viral hepatitis, with a focus on the specific role of IFNλ4 in the host response to HCV. In subproject 1 we will study the biochemistry, physiology, tissue distribution and natural regulation of IFNλ4. In subproject 2 we will study the regulation of the IFNλ receptor. Contrary to the ubiquitous expression of the IFNα receptor in all cell types and organs, IFNλ receptor expression is restricted mainly to epithelial cells. However, its expression can be induced in other cell types such as hepatocytes or dendritic cells. A better understanding of the regulation of IFNλ receptor expression should provide important insights into the biological function of the IFNλ system. In subproject 3 we plan to identify the IFNλ responsive immune cells and to elucidate the cell-cell network and the cytokines involved that regulate the immune response to HCV. Simultaneously with these subprojects focused on the IFNλ system, we plan to develop human biopsy derived liver organoids as an experimental model to study inter-individual differences in cellular responses to HCV and HBV in subproject 4 . Current in vitro models for HCV and HBV are based on few hepatoma derived cell lines and primary human hepatocytes. Both systems have major limitations. Human liver biopsy derived organoids might overcome some of these limitations. Because they can be derived from individual patients they have a unique potential to enable the study of inter-individual differences in cellular responses to hepatitis viruses.
MERiC Research Project | 4 Project MembersCancer is a major health problem due to the failure of current therapies to effectively eradicate the disease. Extensive research over decades has led to the development of therapies that target cancer-specific signaling pathways. However, tumors escape such therapies by activating compensatory signaling pathways, a process referred to as 'evasive resistance'. The identities of the alternative signaling pathways and functional interconnections that underlie evasive resistance remain widely unknown. Elucidating mechanisms of evasive resistance is currently the major challenge in cancer research. We will integrate cutting-edge clinical, molecular, and computational sciences in a pioneering project to understand the signaling defects that enable tumors to evade therapy. With its synergistic, interdisciplinary approach, the proposed project is, to our knowledge, unique in Europe and possibly worldwide. Within the framework of rigorously designed clinical studies, a clinician (PI: M. Heim) will provide basic research scientists with hepatocellular carcinoma (HCC) tissue isolated before therapy, during treatment, or at the time of tumor progression. HCC is chosen as the focal cancer based on medical importance, accessibility to repeated sampling, and ethical considerations. The tumor tissue will be obtained by needle biopsy and immediately snap frozen to preserve in vivo tumor properties. The basic research scientists (PIs: G. Christofori and M. Hall) and a computational biologist (PI: N. Beerenwinkel) will apply high- and low-throughput experimental and computational methods to determine, characterize, and model the underlying signaling defects. Importantly, using longitudinal clinical samples in combination with mouse and cellular HCC model systems, we will define treatment-related changes in cell signaling that allow tumors to circumvent therapy. This process will be iterative such that changes in treatment strategies will again be monitored in the same patient or experimental model. Insights gained will (i) reveal molecular pathomechanisms in oncogenesis, (ii) identify novel drug targets and predictive biomarkers, and (iii) lead to the rational design of personalized medicine that ultimately benefits patients by increasing therapeutic effectiveness and reducing side effects and financial burden. In aggregate, this innovative, comprehensive endeavor will elucidate mechanisms of evasive resistance and will ultimately improve cancer diagnosis, treatment and clinical outcome.
Role of Hepatitis C Virus (HCV) RNA-Dependent RNA Polymerase NS5B activity in HCV pathogenesis, persistence, and regulation of antiviral defense in humans Research Project | 1 Project MembersHepatitis C virus (HCV) is a positive-strand RNA virus infecting approximately 150 million persons worldwide. HCV infection can cause chronic liver disease and lead to liver cirrhosis and/or liver cancer. There is no vaccine for HCV, and current therapy has only limited efficiency and multiple side effects. HCV induces strong innate immune response within first days of infection, that includes production of type I IFN. This response leads to viral clearance in ~30% of patients, however, in other ~70% of cases infection becomes chronic. Mechanisms of HCV persistence and immune escape are poorly understood. For RNA viruses, it is believed that innate immune response is triggered solely by viral genome replication intermediates, such as double-stranded RNA (dsRNA) or 5'-triphosphate-containing (5'-ppp) RNA, generated by viral RNA-dependent RNA polymerases (RdRp). However, this is unlikely for HCV, as its replication takes place in hidden compartments, and viral RNA is, presumably, not exposed to innate immune sensors. It has been demonstrated recently that HCV RdRp (NS5B) can use host cell RNA as template and generate small dsRNA molecules that trigger IFN production in mouse livers and in cultured liver cells. We hypothesize, that this non-specific activity of HCV NS5B protein is the major activator of innate immunity in acute HCV infection in humans, and contributes to HCV persistence and immune regulation in chronic phase. The proposed study will aim at finding out how HCV NS5B activity and production of small dsRNA species affect the course and outcome of HCV infection. We will use human liver biopsies from infected patients, molecular biology and biochemistry techniques, next-generation sequencing and bioinformatics to characterize HCV-induced small dsRNA species and analyze their role in host-virus interactions in HCV infection. A thorough understanding of these interactions will facilitate the development of better therapies and a preventive vaccine.
SX MERiC Mechanisms of Evasive Resistance in Cancer Research Project | 5 Project MembersMechanisms of Evasive Resistance in Cancer Cancer is a major health problem, but current cancer therapies fail to effectively eliminate the disease. The RTD Project MERIC now aims to find out how tumor cells change their signaling pathways to escape treatment. Extensive research over decades has led to the development of therapies that target cancer-specific signaling pathways. Tumors can however escape such therapies by activating compensatory signaling pathways, a process referred to as "evasive resistance". The identities of the alternative signaling pathways and the functional interconnections that underlie evasive resistance remain widely unknown. Elucidating their mechanisms is currently a major challenge in cancer research. Shedding light on the mechanism of evasive resistance To understand the changes in the signaling pathways that enable tumors to evade therapy, the scientists working on the RTD Project MERIC will integrate cutting-edge clinical, computational, and molecular approaches. With the help of rigorously designed clinical studies, the scientists will be able to work with diseased tissue isolated before therapy, during treatment, and at the time of tumor progression. The tissue, chosen based on medical importance, accessibility to repeated sampling, and ethical considerations, will come from hepatocellular carcinoma (HCC). The biomedical scientists and computational biologists in the team will apply high- and low-throughput experimental and computational methods to determine, characterize, and model the underlying signaling defects that allow tumors to circumvent therapy. Following cellular signaling changes of cancer cells over time This research process will be iterative, meaning that the researchers will monitor changes in treatment strategies several times in the same patient or experimental model. This way, they will be able to follow the individual changes in cell signaling of the respective tumors, and track the influence of the medication. Once the molecular pathomechanisms in oncogenesis are revealed, the interdisciplinary MERIC team plans to identify new drug targets and predictive biomarkers. In doing so, they hope to contribute to the rational design of personalized medicine approaches by increasing therapeutic efficacy and reducing side effects and the financial burden of treatment for the benefit of the patient.
Innate Immune Responses to Hepatitis C Virus Infections Research Project | 1 Project MembersChronic hepatitis C (CHC) is a major cause of chronic liver disease. An important and striking feature of hepatitis C virus (HCV) is its tendency toward chronicity. In > 70% of infected individuals, HCV establishes a persistent infection over decades that may lead to cirrhosis and hepatocellular carcinoma. This high rate of persistence is linked to an ability of HCV to evade and antagonize the immune response of the host. Type I interferons (IFNs) are crucial and potent components of the early host response against virus infection and recombinant pegylated IFNα (pegIFNα) in combination with ribavirin is the current standard therapy for CHC. About half of the patients can be cured. In the current research grant application, we plan to address several key points of the innate immune response to hepatitis C virus infection. 1. Analysis of liver biopsies of HCV infected patients with a newly developed fluorescence in situ hybridization method (FISH). We will use a newly developed FISH method to visualize and quantify HCV RNA and mRNAs of IFNs and IFN stimulated genes in liver biopsies. 2. IFNα induced signaling in the human liver. The pharmacodynamic effects of pegylated IFNα will be studied in liver biopsies obtained at different time points during the week after the first injection of pegylated IFNα in patients with CHC . 3. The role of IFNλ in establishing and maintaining IFN stimulated gene expression in the liver of HCV infected patients. We plan to systematically study IFNλ and IFNλ receptor expression in liver biopsies of patients with chronic hepatitis C (and controls) and correlate the status of the IFNλ system with hepatic IFN stimulated gene expression. We will investigate the molecular mechanisms that links IL28B genotype with IFN stimulated gene expression and with non-response to pegIFN-α/ribavirin combination therapies. 4. Functional characterization of IFNα induced long non-coding RNAs (lncRNAs) We have identified hundreds of lncRNAs that are induced by IFNα. We plan to study if some of them have a role in negative regulation of genes by IFNα.
Interferon Signaling and Innate Immunity in Chronic Viral Hepatitis Research Project | 1 Project MembersNo Description available
Systems Biology of hepatic insulin resistance Research Project | 1 Project MembersNo Description available
Hepatocarcinogenesis in chronic hepatitis C Research Project | 1 Project MembersNo Description available
