Dr Daniel Felmlee
Profiles

Dr Daniel Felmlee

Lecturer in Hepatology

Biomedical Research - Institute of Translational & Stratified Medicine (Plymouth University Peninsula Schools of Medicine and De

Role

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 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).

Key publications are highlighted

Journals
Articles
Shawa IT, Felmlee DJ, Hegazy D, Sheridan DA & Cramp ME 2017 'Exploration of potential mechanisms of HCV resistance in exposed uninfected intravenous drug users' Journal of Viral Hepatitis , DOI PEARL
Bassendine MF, Nielsen SU, Bridge SH, Felmlee DJ, Sheridan DA, Packard CJ & Neely RD 2017 'Hepatitis C virus and atherosclerosis: A legacy after virologic cure?' Clinics and Research in Hepatology and Gastroenterology 41, (1) 25-30 , DOI
Verrier ER, Colpitts CC, Bach C, Heydmann L, Weiss A, Renaud M, Durand SC, Habersetzer F, Durantel D & Abou-Jaoudé G 2016 '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
Fauvelle C, Felmlee DJ, Crouchet E, Lee J, Heydmann L, Lefèvre M, Magri A, Hiet M-S, Fofana I & Habersetzer F 2016 'Apolipoprotein E Mediates Evasion From Hepatitis C Virus Neutralizing Antibodies' Gastroenterology 150, (1) 206-217.e4 , DOI
Felmlee DJ & Baumert TF 2016 'CD147 handles lipid: a new role for anti-cancer target' Translational Cancer Research 5, (3) 238-240 , DOI
Felmlee DJ, Coilly A, Chung RT, Samuel D & Baumert TF 2016 'New perspectives for preventing hepatitis C virus liver graft infection' The Lancet Infectious Diseases 16, (6) 735-745 , DOI
Ahmed A & Felmlee D 2015 'Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals' Viruses 7, (12) 6716-6729 , DOI
Sheridan DA, Gomez Romero M, Bridge S, Crossey M, Shawa IT, Neely D, Felmlee D, Holmes E, Bassendine M & Taylor-Robinson S 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
Bridge SH, Sheridan DA, Felmlee DJ, Crossey MME, Fenwick FI, Lanyon CV, Dubuc G, Seidah NG, Davignon J & Thomas HC 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 PEARL
Sheridan DA, Bridge SH, Crossey MME, Felmlee DJ, Thomas HC, Neely RDG, Taylor-Robinson SD & Bassendine MF 2014 'Depressive symptoms in chronic hepatitis C are associated with plasma apolipoprotein E deficiency' Metabolic Brain Disease 29, (3) 625-634 , DOI
Baumert TF, Meredith L, Ni Y, Felmlee DJ, McKeating JA & Urban S 2014 'Entry of hepatitis B and C viruses — recent progress and future impact' Current Opinion in Virology 4, 58-65 , DOI
Felmlee DJ, Schuster C & Baumert TF 2014 'New tool for the study of hepatitis C virus genotype 3 and its associated liver disease biology' Hepatology 60, (6) 1806-1808 , DOI
Felmlee DJ, Fauvelle C, Le Févre M, Heydmann L, Hiet M-S, Bartenschlager R, Fofana I, Habersetzer F, Milne R & Patel A 2014 'O52 APOLIPOPROTEIN E MEDIATES HCV ESCAPE FROM HOST NEUTRALIZING ANTIBODIES' Journal of Hepatology 60, (1) S21-S21 , DOI
Sheridan DA, Bridge SH, Crossey MME, Felmlee DJ, Fenwick FI, Thomas HC, Neely RDG, Taylor-Robinson SD & Bassendine MF 2014 '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
Lefèvre M, Felmlee DJ, Parnot M, Baumert TF & Schuster C 2014 'Syndecan 4 Is Involved in Mediating HCV Entry through Interaction with Lipoviral Particle-Associated Apolipoprotein E' PLoS ONE 9, (4) e95550-e95550 , DOI PEARL
Fauvelle C, Felmlee DJ & Baumert TF 2014 'Unraveling hepatitis C virus structure' Cell Research 24, (4) 385-386 , DOI
Felmlee DJ, Fauvelle C, Heydmann L, Hiet M-S, Fofana I, Bartenschlager R, Stoll-Keller F, Zeisel MB, Fafi-Kremer S & Baumert TF 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
Sheridan DA, Felmlee DJ, Bridge SH, Fenwick F, Askew B, Neely D, Crossey MME, Taylor-Robinson SD, Toms GL & Bassendine MF 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
Sheridan DA, Bridge SH, Crossey MME, Felmlee DJ, Fenwick F, Thomas HC, Neely D, Taylor-Robinson SD & Bassendine MF 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
Felmlee DJ & Baumert TF 2013 'Hepatitis C virus co-opts innate immunity component for lipid droplet formation' Journal of Hepatology 59, (5) 1118-1120 , DOI
Zeisel MB, Felmlee DJ & Baumert TF 2013 'Hepatitis C Virus Entry' HEPATITIS C VIRUS: FROM MOLECULAR VIROLOGY TO ANTIVIRAL THERAPY 369, 87-112 Author Site , DOI
Fauvelle C, Lepiller Q, Felmlee DJ, Fofana I, Habersetzer F, Stoll-Keller F, Baumert TF & Fafi-Kremer S 2013 'Hepatitis C virus vaccines – Progress and perspectives' Microbial Pathogenesis 58, 66-72 , DOI
Felmlee D, Hafirassou M, Lefevre M, Baumert T & Schuster C 2013 'Hepatitis C Virus, Cholesterol and Lipoproteins — Impact for the Viral Life Cycle and Pathogenesis of Liver Disease' Viruses 5, (5) 1292-1324 , DOI PEARL
Lupberger J, Felmlee DJ & Baumert TF 2013 'Interferon-lambda polymorphisms and hepatitis C virus clearance revisited' Hepatology 58, (1) 439-441 , DOI
Bassendine MF, Sheridan DA, Bridge SH, Felmlee DJ & Neely RDG 2013 'Lipids and HCV' Seminars in Immunopathology 35, (1) 87-100 , DOI
Felmlee DJ, Xiao F & Baumert TF 2013 'Modeling the antiviral activity of ribavirin against hepatitis C virus in cell culture' Hepatology 58, (4) 1203-1206 , DOI
Sheridan DA, Bridge SH, Felmlee DJ, Crossey MME, Thomas HC, Taylor-Robinson SD, Toms GL, Neely RDG & Bassendine MF 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
Lupberger J, Felmlee DJ & Baumert TF 2012 'Cholesterol uptake and hepatitis C virus entry' Journal of Hepatology 57, (1) 215-217 , DOI
Fafi-Kremer S, Fauvelle C, Felmlee DJ, Zeisel MB, Lepiller Q, Fofana I, Heydmann L, Stoll-Keller F & Baumert TF 2012 'Neutralizing Antibodies and Pathogenesis of Hepatitis C Virus Infection' Viruses 4, (12) 2016-2030 , DOI PEARL
Da Costa D, Turek M, Felmlee DJ, Girardi E, Pfeffer S, Long G, Bartenschlager R, Zeisel MB & Baumert TF 2012 'Reconstitution of the Entire Hepatitis C Virus Life Cycle in Nonhepatic Cells' Journal of Virology 86, (21) 11919-11925 , DOI
Sheridan P, Bridge S, Felmlee D, Taylor Robinson S, Thomas H, Toms G, Neely D & Bassendine M 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
Sheridan D, Crossey M, Thomas H, Taylor Robinson S, Felmlee D, Bridge S, Toms G, Neely D & Bassendine M 2011 '473 DEPRESSION IN CHRONIC HEPATITIS C IS ASSOCIATED WITH LOW APOLIPOPROTEIN E LEVELS' Journal of Hepatology 54, S193-S193 , DOI
Bassendine MF, Sheridan DA, Felmlee DJ, Bridge SH, Toms GL & Neely RDG 2011 'HCV and the hepatic lipid pathway as a potential treatment target' Journal of Hepatology 55, (6) 1428-1440 , DOI
Bridge SH, Sheridan DA, Felmlee DJ, Nielsen SU, Thomas HC, Taylor-Robinson SD, Neely RDG, Toms GL & Bassendine MF 2011 'Insulin resistance and low-density apolipoprotein B-associated lipoviral particles in hepatitis C virus genotype 1 infection' Gut 60, (5) 680-687 , DOI
Felmlee D, Sheridan D, Bridge S, Packard C, Caslake M, Toms G, Neely D & Bassendine M 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
Bridge S, Sheridan D, Felmlee D, Crossey M, Thomas H, Taylor-Robinson S, Toms G, Neely D & Bassendine M 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
Sheridan D, Bridge S, Felmlee D, Robinson ST, Thomas H, Toms G, Neely D & Bassendine M 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
Sheridan D, Bartlett K, Felmlee D, Bridge SH, Toms GL, Dubuc G, Nabil S, Davignon J, Neely D & Bassendine MF 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
Bridge SH, Sheridan DA, Felmlee DJ, Nielsen SU, Neely RDG, Toms GL & Bassendine MF 2010 '1079 INSULIN RESISTANCE CORRELATES WITH LOW DENSITY HEPATITIS C VIRUS PARTICLES IN GENOTYPE 1 INFECTION' Journal of Hepatology 52, S417-S417 , DOI
Sheridan DA, Bartlett K, Felmlee DJ, Bridge SH, Toms GL, Dubuc G, Seidah NG, Davignon J, Neely RDG & Bassendine MF 2010 'Hypocholesterolaemia in chronic Hepatitis C virus (HCV) infection – Reduced production or increased LDL clearance?' Atherosclerosis 213, (1) e4-e4 , DOI
Felmlee DJ, Sheridan DA, Bridge SH, Nielsen SU, Milne RW, Packard CJ, Caslake MJ, McLauchlan J, Toms GL & Neely RDG 2010 'Intravascular Transfer Contributes to Postprandial Increase in Numbers of Very-Low-Density Hepatitis C Virus Particles' Gastroenterology 139, (5) 1774-1783.e6 , DOI
Bridge SH, Sheridan DA, Felmlee DJ, Toms GL, Neely RDG & Bassendine MF 2010 'Low density Hepatitis C virus particles (lipoviral particles) associate with insulin resistance in genotype 1 infection' Atherosclerosis 213, (1) e4-e4 , DOI
Nielsen S, Sheridan D, Bridge S, Felmlee D, Neely D, Toms G & Bassendine M 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
Waris G, Felmlee DJ, Negro F & Siddiqui A 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
Domitrovich AM, Felmlee DJ & Siddiqui A 2005 'Hepatitis C Virus Nonstructural Proteins Inhibit Apolipoprotein B100 Secretion' Journal of Biological Chemistry 280, (48) 39802-39808 , DOI
Conference Papers
Ahmed A, Dhanda A, Hegazy D, Felmlee D, Sheridan D & Cramp M 2016 'Sustained viral clearance of HCV with DAA treatment is associated with restoration of effector T cell phenotype' //0 //0 745A-745A
Sheridan DA, Romero MG, Bridge S, Crossey M, Shawa IT, Neely D, Felmlee D, Holmes E, Bassendine M & Taylor-Robinson S 2015 'LIPIDOMICS ANALYSIS OF FASTING SERUM IDENTIFIES NOVEL LIPID BIOMARKERS SPECIFIC FOR HCV GENOTYPE 3 AND GENOTYPE 1 CHRONIC HEPATITIS C VIRUS INFECTION' //0 //0 S596-S596
Felmlee DJ, Fauvelle C, Le Fevre M, Heydmann L, Hiet M-S, Bartenschlager R, Fofana I, Habersetzer F, Milne R & Patel A 2014 'APOLIPOPROTEIN E MEDIATES HCV ESCAPE FROM HOST NEUTRALIZING ANTIBODIES' //0 //0 S21-S21
Felmlee DJ, Fauvelle C, Heydmann L, Hiet M-S, Fofana I, Bartenschlager R, Stoll-Keller F, Zeisel MB, Fafi-Kremer S & Baumert TF 2013 'HEPATITIS C VIRUS LIVER TRANSPLANTATION ESCAPE VARIANT IS CHARACTERIZED BY BOTH ENHANCED TRIGLYCERIDE-RICH LIPOPROTEIN ASSOCIATION AND SENSITIVITY TO apoE ANTIBODIES' //0 //0 S468-S468