- Research Wing, John Bull Building, Research Way, Plymouth, PL6 8BU
- +44 1752 437415
- daniel.felmlee@plymouth.ac.uk
Profiles
Dr Daniel Felmlee
Lecturer in Hepatology
Peninsula Medical School (Faculty of Health)
Biography
Biography
Academic Lecturer in Hepatology
Qualifications
PhD Molecular Biology, University of Colorado Medical School
Thesis Title: Hepatitis C alters lipid and lipoprotein metabolism
Hepatits C virus (HCV) infection is a major health problem and the leading indication for liver transplantation in the US and Europe. HCV infection associates with disorders in lipid and lipoprotein metabolism including hepatic steatosis, an accumulation of fat in the liver. My previous work at University of Colorado School of Medicine, then University of California, San Diego focused on how HCV replication changes lipoprotein secretion from hepatoma cell lines, leading to lipid accumulation.
Following my interest in virus-host interactions of viral hepatitis, I pursued an MRC postdoc position in Newcastle upon Tyne investigating HCV virus/lipoprotein hybrid particles, lipoviral particles (LVP). I developed and collaboratively executed clinically based experiments that revealed LVPs to be dynamic transient particles dependent on host lipoprotein metabolism and external factors such as diet.
I then pursued and won a competitive fellowship from European Association for Study of the Liver (EASL) in Strasbourg, France. I used state-of-the-art molecular virology techniques using tissue culture models of HCV infection to further investigate functional relevance of lipoprotein and apolipoprotein interactions for viral entry and escape from host humoral defences.
Professional membership
Editorial Board Member, World Journal of Hepatology
Reviewer, Journal of Infectious Diseases
Reviewer, Virology
Research
Research
Research interests
Primary Interest
Hepatitis C virus (HCV) infection is a major health problem with 3% of the global population infected. The natural history of HCV typically involves chronic infection resulting in hepatitis, fibrosis, cirrhosis, and end stage liver disease. A number of individuals who through risk factors or known exposure have been exposed to the virus, but neither have HCV RNA detectable in serum nor detectable anti-HCV antibodies. These exposed yet uninfected patients (EUs) appear to have either robust immune defences or other uncharacterized resistance to HCV infection. In the course of genome analysis of these individuals, we have identified candidate genes that are highly associated with HCV resistance. I seek to further characterize these genes through functional analysis using tissue culture HCV replication models.
Future studies will also focus on characterization of hepatitis B virus (HBV) in newly developed cell culture models and developing models of study for non-alcoholic fatty liver disease (NAFLD) and further inflammation signals that develop to non-alcoholic steatohepatitis (NASH).
Research groups
Publications
Publications
Key publications
Key publications are highlighted
Journals
Articles
(2022) 'Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis' Scientific Reports 12, (1) , DOI Open access
(2020) 'Retraction for Waris et al., “Hepatitis C Virus Induces Proteolytic Cleavage of Sterol Regulatory Element Binding Proteins and Stimulates Their Phosphorylation via Oxidative Stress”' Journal of Virology 94, (19) , DOI
(2017) 'Lipid interactions influence hepatitis C virus susceptibility and resistance to infection' Clinical Liver Disease 10, (1) 17-20 , DOI Open access
(2017) 'Exploration of potential mechanisms of HCV resistance in exposed uninfected intravenous drug users' Journal of Viral Hepatitis , DOI Open access
(2016) 'Hepatitis C virus and atherosclerosis: A legacy after virologic cure?' Clinics and Research in Hepatology and Gastroenterology 41, (1) 25-30 , DOI Open access
(2016) 'CD147 handles lipid: a new role for anti-cancer target' Translational Cancer Research 5, (3) 238-240 , DOI Open access
(2016) 'New perspectives for preventing hepatitis C virus liver graft infection' The Lancet Infectious Diseases 16, (6) 735-745 , DOI Open access
(2016) 'Apolipoprotein E Mediates Evasion From Hepatitis C Virus Neutralizing Antibodies' Gastroenterology 150, (1) 206-217.e4 , DOI
(2015) 'Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals' Viruses 7, (12) 6716-6729 , DOI Open access
(2015) 'A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses' Hepatology 63, (1) 35-48 , DOI
(2015) 'P0725 : Lipidomics analysis of fasting serum identifies novel lipid biomarkers specific for HCV genotype 3 and genotype 1 chronic hepatitis C virus infection' Journal of Hepatology 62, S596-S596 , DOI
(2015) 'PCSK9, apolipoprotein E and lipoviral particles in chronic hepatitis C genotype 3: Evidence for genotype-specific regulation of lipoprotein metabolism' Journal of Hepatology 62, (4) 763-770 , DOI Open access
(2014) 'New tool for the study of hepatitis C virus genotype 3 and its associated liver disease biology' Hepatology 60, (6) 1806-1808 , DOI
(2014) 'Syndecan 4 Is Involved in Mediating HCV Entry through Interaction with Lipoviral Particle-Associated Apolipoprotein E' PLoS ONE 9, (4) 0-0 , DOI Open access
(2014) 'O52 APOLIPOPROTEIN E MEDIATES HCV ESCAPE FROM HOST NEUTRALIZING ANTIBODIES' Journal of Hepatology 60, (1) S21-S21 , DOI
(2014) 'Depressive symptoms in chronic hepatitis C are associated with plasma apolipoprotein E deficiency' Metabolic Brain Disease 29, (3) 625-634 , DOI
(2014) 'Entry of hepatitis B and C viruses — recent progress and future impact' Current Opinion in Virology 4, 58-65 , DOI
(2013) 'Hepatitis C virus co-opts innate immunity component for lipid droplet formation' Journal of Hepatology 59, (5) 1118-1120 , DOI
(2013) 'Omega-3 fatty acids and/or fluvastatin in hepatitis C prior non-responders to combination antiviral therapy - a pilot randomised clinical trial' Liver International 34, (5) 737-747 , DOI
(2013) 'Epidermal growth factor receptor signaling impairs the antiviral activity of interferon-alpha' Hepatology 58, (4) 1225-1235 , DOI
(2013) 'Modeling the antiviral activity of ribavirin against hepatitis C virus in cell culture' Hepatology 58, (4) 1203-1206 , DOI
(2013) 'Hepatitis C Virus, Cholesterol and Lipoproteins — Impact for the Viral Life Cycle and Pathogenesis of Liver Disease' Viruses 5, (5) 1292-1324 , DOI Open access
(2013) 'Interferon-lambda polymorphisms and hepatitis C virus clearance revisited' Hepatology 58, (1) 439-441 , DOI
(2013) 'Hepatitis C virus vaccines – Progress and perspectives' Microbial Pathogenesis 58, 66-72 , DOI
(2013) '1150 HEPATITIS C VIRUS LIVER TRANSPLANTATION ESCAPE VARIANT IS CHARACTERIZED BY BOTH ENHANCED TRIGLYCERIDE-RICH LIPOPROTEIN ASSOCIATION AND SENSITIVITY TO apoE ANTIBODIES' Journal of Hepatology 58, S468-S468 , DOI
(2013) '493 METABOLIC SYNDROME AND INSULIN RESISTANCE ARE ASSOCIATED WITH MAXIMUM HEPATITIS C LIPOVIRAL PARTICLES IN GENOTYPE 1 INFECTION' Journal of Hepatology 58, S202-S202 , DOI
(2013) '903 OMEGA-3 FATTY ACIDS AND/OR FLUVASTATIN IN HEPATITIS C PRIOR NON-RESPONDERS TO COMBINATION ANTI-VIRAL THERAPY – A PILOT RANDOMISED CLINICAL TRIAL' Journal of Hepatology 58, S372-S372 , DOI
(2013) 'Hepatitis C Virus Entry' HEPATITIS C VIRUS: FROM MOLECULAR VIROLOGY TO ANTIVIRAL THERAPY 369, 87-112 , DOI
(2012) 'Reconstitution of the Entire Hepatitis C Virus Life Cycle in Nonhepatic Cells' Journal of Virology 86, (21) 11919-11925 , DOI
(2012) 'Neutralizing Antibodies and Pathogenesis of Hepatitis C Virus Infection' Viruses 4, (10) 2016-2030 , DOI Open access
(2012) 'Apolipoprotein-E and hepatitis C lipoviral particles in genotype 1 infection: Evidence for an association with interferon sensitivity' Journal of Hepatology 57, (1) 32-38 , DOI
(2011) 'HCV and the hepatic lipid pathway as a potential treatment target' Journal of Hepatology 55, (6) 1428-1440 , DOI
(2011) 'P44 Use of Intralipid infusion to analyse apolipoprotein B (apoB) and HCV RNA kinetics in chronic infection' Gut 60, (Suppl 2) A21-A21 , DOI
(2011) 'P50 Apolipoprotein E and low-density, apolipoprotein B associated lipoviral particles in chronic hepatitis C infection: evidence for genotype-specific modulation of lipid pathways' Gut 60, (Suppl 2) A24-A24 , DOI
(2011) 'The 'interferon paradox' as a predictor of non-response to anti-viral therapy: novel association with apolipoprotein E and hepatitis C virus (HCV) lipoviralparticles (LVP)' Gut 60, (Suppl 1) A55-A56 , DOI
(2011) '1183 THE “INTERFERON PARADOX” AS A PREDICTOR OF NON-RESPONSE TO ANTI-VIRAL THERAPY: NOVEL ASSOCIATION WITH APOLIPOPROTEIN E AND HEPATITIS C VIRUS (HCV) LIPOVIRAL PARTICLES (LVP)' Journal of Hepatology 54, S467-S467 , DOI
(2011) '473 DEPRESSION IN CHRONIC HEPATITIS C IS ASSOCIATED WITH LOW APOLIPOPROTEIN E LEVELS' Journal of Hepatology 54, S193-S193 , DOI
(2010) 'Hypocholesterolaemia in chronic Hepatitis C virus (HCV) infection – Reduced production or increased LDL clearance?' Atherosclerosis 213, (1) e4-e4 , DOI
(2010) 'Intravascular Transfer Contributes to Postprandial Increase in Numbers of Very-Low-Density Hepatitis C Virus Particles' Gastroenterology 139, (5) 1774-1783.e6 , DOI
(2010) 'Low density Hepatitis C virus particles (lipoviral particles) associate with insulin resistance in genotype 1 infection' Atherosclerosis 213, (1) e4-e4 , DOI
(2010) 'Insulin resistance and low-density apolipoprotein B-associated lipoviral particles in hepatitis C virus genotype 1 infection' Gut 60, (5) 680-687 , DOI
(2010) 'OP14 Measurement of low density apolipoprotein B associated hepatitis C virus lipoviral particles in genotype 1 infection is more clinically relevant than total viral load' Gut 59, (Suppl 2) , DOI
(2010) '1078 HYPOCHOLESTEROLAEMIA IN CHRONIC HEPATITIS C GENOTYPE 3 INFECTION IS DUE TO BOTH REDUCED CHOLESTEROL PRODUCTION AND INCREASED LDL CLEARANCE' Journal of Hepatology 52, S417-S417 , DOI
(2010) '1079 INSULIN RESISTANCE CORRELATES WITH LOW DENSITY HEPATITIS C VIRUS PARTICLES IN GENOTYPE 1 INFECTION' Journal of Hepatology 52, S417-S417 , DOI
(2009) '869 CHARACTERIZATION OF HEPATITIS C VIRUS PARTICLES IN HUMAN PLASMA: ASSOCIATION WITH IMMUNOGLOBULINS G1, G3 & M AND APOLIPOPROTEINS A-I, A-II, B, C-I AND E' Journal of Hepatology 50, S316-S317 , DOI
(2007) 'Hepatitis C Virus Induces Proteolytic Cleavage of Sterol Regulatory Element Binding Proteins and Stimulates Their Phosphorylation via Oxidative Stress' Journal of Virology 81, (15) 8122-8130 , DOI
(2005) 'Hepatitis C Virus Nonstructural Proteins Inhibit Apolipoprotein B100 Secretion' Journal of Biological Chemistry 280, (48) 39802-39808 , DOI
Chapters
(2013) 'Hepatitis C Virus Entry' Current Topics in Microbiology and Immunology Springer Berlin Heidelberg 87-112 , DOI
Conference Papers
(2016) 'Sustained viral clearance of HCV with DAA treatment is associated with restoration of effector T cell phenotype' 745A-745A
(2015) 'PTH-100 A comparative gene expression study between individuals with apparent resistance, spontaneous clearance, or chronic infection from hcv' BMJ A452.1-A452 , DOI
(2015) 'LIPIDOMICS ANALYSIS OF FASTING SERUM IDENTIFIES NOVEL LIPID BIOMARKERS SPECIFIC FOR HCV GENOTYPE 3 AND GENOTYPE 1 CHRONIC HEPATITIS C VIRUS INFECTION' S596-S596 , DOI
(2014) 'Apolipoprotein E Functionally Obscures Hepatitis C Virus from Neutralizing Antibodies' 1064A-1064A
(2014) 'High-throughput hepatitis B and D virus model systems for discovery of targets for viral cure' 1038A-1038A
(2013) 'Syndecan 4 is the primary heparan sulfate proteoglycan mediating HCV entry through interaction with apolipoprotein E' 927A-927A
(2013) 'HEPATITIS C VIRUS LIVER TRANSPLANTATION ESCAPE VARIANT IS CHARACTERIZED BY BOTH ENHANCED TRIGLYCERIDE-RICH LIPOPROTEIN ASSOCIATION AND SENSITIVITY TO apoE ANTIBODIES' S468-S468 , DOI
(2013) 'METABOLIC SYNDROME AND INSULIN RESISTANCE ARE ASSOCIATED WITH MAXIMUM HEPATITIS C LIPOVIRAL PARTICLES IN GENOTYPE 1 INFECTION' S202-S202 , DOI
(2013) 'OMEGA-3 FATTY ACIDS AND/OR FLUVASTATIN IN HEPATITIS C PRIOR NON-RESPONDERS TO COMBINATION ANTI-VIRAL THERAPY - A PILOT RANDOMISED CLINICAL TRIAL' S372-S372 , DOI
(2012) 'Reconstitution of the entire hepatitis C virus life cycle in a non-hepatic cell line' 704A-704A
(2011) 'APOLIPOPROTEIN E AND LOW-DENSITY, APOLIPOPROTEIN B ASSOCIATED LIPOVIRAL PARTICLES IN CHRONIC HEPATITIS C INFECTION: EVIDENCE FOR GENOTYPE-SPECIFIC MODULATION OF LIPID PATHWAYS' 1316A-1316A
(2011) 'USE OF INTRALIPID INFUSION TO ANALYSE APOLIPOPROTEIN B (APOB) AND HCV RNA KINETICS IN CHRONIC INFECTION' 1320A-1320A
(2011) 'Depression in chronic hepatitis C is associated with low apolipoprotein e levels' BMJ A58-A58 , DOI
(2011) 'DEPRESSION IN CHRONIC HEPATITIS C IS ASSOCIATED WITH LOW APOLIPOPROTEIN E LEVELS' S193-S193 , DOI
(2011) 'THE "INTERFERON PARADOX" AS A PREDICTOR OF NON-RESPONSE TO ANTI-VIRAL THERAPY: NOVEL ASSOCIATION WITH APOLIPOPROTEIN E AND HEPATITIS C VIRUS (HCV) LIPOVIRAL PARTICLES (LVP)' S467-S467
(2010) 'MEASUREMENT OF LOW-DENSITY APOLIPOPROTEIN B ASSOCIATED LIPOVIRAL PARTICLES IN HEPATITIS C VIRUS GENOTYPE 1 INFECTION IS MORE CLINICALLY RELEVANT THAN TOTAL VIRAL LOAD' 435A-435A
(2010) 'THE HCV LIFE-CYCLE IN THE VASCULAR COMPARTMENT' 819A-820A
(2010) 'HYPOCHOLESTEROLAEMIA IN CHRONIC HEPATITIS C GENOTYPE 3 INFECTION IS DUE TO BOTH REDUCED CHOLESTEROL PRODUCTION AND INCREASED LDL CLEARANCE' S417-S417 , DOI
(2010) 'INSULIN RESISTANCE CORRELATES WITH LOW DENSITY HEPATITIS C VIRUS PARTICLES IN GENOTYPE 1 INFECTION' S417-S417 , DOI
(2009) 'APOLIPOPROTEIN B ASSOCIATED HEPATITIS C VIRUS (HCV): A MINORITY OF TOTAL VIRAL LOAD IN PATIENTS WITH CHRONIC HCV' 1061A-1061A
(2009) 'LARGE AND BUOYANT HEPATITIS C VIRUS (HCV) PARTICLES SURGE AFTER PATIENTS CONSUME A HIGH-FAT MEAL' 314A-314A
(2009) 'CHARACTERIZATION OF HEPATITIS C VIRUS PARTICLES IN HUMAN PLASMA: ASSOCIATION WITH IMMUNOGLOBULINS G1, G3 & M AND APOLIPOPROTEINS A-I, A-II, B, C-I AND E' S316-S317 , DOI
(2006) 'Hepatitis C virus inhibits apolipoprotein B100 secretion' A1267-A1267