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Susan L. Uprichard Photo
Name
Susan L. Uprichard
Degree
Ph.D.
Rank
Professor
Primary Department
Hepatology
Joint Department
Microbiology and Immunology
Appointment Request
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Education
Advanced Degrees
Harvard University , Cambridge , MA , United States
Summaries
The focus of my research program is hepatitis viruses with an emphasis on hepatitis C virus (HCV) and hepatitis B virus (HBV). Although HCV and HBV represents significant public health burdens, research efforts to understand these viral infections infection have been hindered by the lack of experimental systems. For this reason, one initial and continuing focus of the laboratory is the establishment, characterization, and optimization of the experimental in vitro cell culture and in vivo mouse models needed to dissect the HCV and HBV life cycles, identify effective antiviral strategies, understand molecular mechanisms of associated liver disease, and identify the viral-host interactions that determine the outcome of infection (i.e. clearance versus chronicity) Ongoing projects utilizing our established infectious HCV cell culture systems include: (1) the study of the viral-host interactions that regulate viral entry and cell-to-cell spread (including elucidating the role two HCV entry factors we have discovered, i.e. NPC1L1 and TfR1); (2) investigating the role host cell lipid pathways in HCV infection (with a focus on factors we specifically identified via genomic RNAi screening as being involved in viral infection; (3) development and use of mathematical models to understand HCV infection dynamics and response to antiviral therapy. Ongoing HBV projects include: (1) Optimization of the currently new but inefficient HBV cell culture infection systemÂ’ (2) Characterization of the humanized chimeric mouse model of HBV infectionÂ’ (3) Investigating the viral-host interactions that regulate viral entry and determine the extent to which HBV can spread directly via cell-to-cell transmission
Keywords
Antivirals
Hepatitis
Infectious Diseases/Agents
Mathematical Modeling
Molecular Microbiology
Translational Research
Publications
Aunins,T. R.; Marsh,K. A.; Subramanya,G.; Uprichard,S. L.; Perelson,A. S.; Chatterjee,A.Intracellular hepatitis C modeling predicts infection dynamics and viral protein mechanisms Journal of virology 2018 ; :
Ishida,Y.; Chung,T. L.; Imamura,M.; Hiraga,N.; Sen,S.; Yokomichi,H.; Tateno,C.; Canini,L.; Perelson,A. S.; Uprichard,S. L.; Dahari,H.; Chayama,K.Acute HBV infection in humanized chimeric mice has multiphasic viral kinetics Hepatology (Baltimore, Md.) 2018 ; :
Malespin,M.; Benyashvili,T.; Uprichard,S. L.; Perelson,A. S.; Dahari,H.; Cotler,S. J.Prevalence of end of treatment RNA-positive/sustained viral response in HCV patients treated with sofosbuvir combination therapies Therapeutic advances in gastroenterology 2017 ;10(1):68-73
Nguyen,T. H. T.; Guedj,J.; Uprichard,S. L.; Kohli,A.; Kottilil,S.; Perelson,A. S.The paradox of highly effective sofosbuvir-based combination therapy despite slow viral decline: can we still rely on viral kinetics? Scientific reports 2017 ;7(1):10233-017-09776-z
Canini,L.; Imamura,M.; Kawakami,Y.; Uprichard,S. L.; Cotler,S. J.; Dahari,H.; Chayama,K.HCV kinetic and modeling analyses project shorter durations to cure under combined therapy with daclatasvir and asunaprevir in chronic HCV-infected patients PLoS ONE 2017 ;12(12):e0187409
Goyal,A.; Lurie,Y.; Meissner,E. G.; Major,M.; Sansone,N.; Uprichard,S. L.; Cotler,S. J.; Dahari,H.Modeling HCV cure after an ultra-short duration of therapy with direct acting agents Antiviral Research 2017 ;144:281-285
Canini,L.; Koh,C.; Cotler,S. J.; Uprichard,S. L.; Winters,M. A.; Han,M. A. T.; Kleiner,D. E.; Idilman,R.; Yurdaydin,C.; Glenn,J. S.; Heller,T.; Dahari,H.Pharmacokinetics and pharmacodynamics modeling of lonafarnib in patients with chronic hepatitis delta virus infection Hepatology communications 2017 ;1(4):288-292
Hasin Y, Shteingart S, Dahari H, Gafanovich I, Floru S, Braun M, Shlomai A, Verstandig A, Dery I, Uprichard SL, Cotler SJ, Lurie YHepatitis C virus cures after direct acting antiviral-related drug-induced liver injury WORLD JOURNAL OF HEPATOLOGY 2016 ;8(20):858-862
Dahari,H.; Canini,L.; Graw,F.; Uprichard,S. L.; Araujo,E. S.; Penaranda,G.; Coquet,E.; Chiche,L.; Riso,A.; Renou,C.; Bourliere,M.; Cotler,S. J.; Halfon,P.HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir Journal of Hepatology 2016 ; :
Hasin,Y.; Shteingart,S.; Dahari,H.; Gafanovich,I.; Floru,S.; Braun,M.; Shlomai,A.; Verstandig,A.; Dery,I.; Uprichard,S. L.; Cotler,S. J.; Lurie,Y.Hepatitis C virus cures after direct acting antiviral-related drug-induced liver injury: Case report WORLD JOURNAL OF HEPATOLOGY 2016 ;8(20):858-862
DebRoy,S.; Hiraga,N.; Imamura,M.; Hayes,C. N.; Akamatsu,S.; Canini,L.; Perelson,A. S.; Pohl,R. T.; Persiani,S.; Uprichard,S. L.; Tateno,C.; Dahari,H.; Chayama,K.Hepatitis C virus dynamics and cellular gene expression in uPA-SCID chimeric mice with humanized livers during intravenous silibinin monotherapy Journal of viral hepatitis 2016 ; :
Uprichard,S. L.; Sainz,B.,JrInhibition of hepatitis C entry: too soon to dismiss while many are still being denied treatment Gut 2015 ;64(4):690-691
Koh,C.; Canini,L.; Dahari,H.; Zhao,X.; Uprichard,S. L.; Haynes-Williams,V.; Winters,M. A.; Subramanya,G.; Cooper,S. L.; Pinto,P.; Wolff,E. F.; Bishop,R.; Ai Thanda Han,M.; Cotler,S. J.; Kleiner,D. E.; Keskin,O.; Idilman,R.; Yurdaydin,C.; Glenn,J. S.; Heller,T.Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial The Lancet.Infectious diseases 2015 ;15(10):1167-1174
Graw,F.; Martin,D. N.; Perelson,A. S.; Uprichard,S. L.; Dahari,H.Quantification of Hepatitis C Virus Cell-to-Cell Spread Using a Stochastic Modeling Approach Journal of virology 2015 ;89(13):6551-6561
Uprichard,S. L.Establishment of mice with inheritable susceptibility to productive hepatitis C virus infection Hepatology (Baltimore, Md.) 2014 ;59(5):2043-2046
Sabahi,A.; Uprichard,S. L.; Wimley,W. C.; Dash,S.; Garry,R. F.Minireview: Unexpected structural features of the hepatitis c virus envelope protein 2 ectodomain Journal of virology 2014 ;88(18):10280-10288
Sabahi,A.; Uprichard,S. L.; Wimley,W. C.; Dash,S.; Garry,R. F.Unexpected structural features of the hepatitis C virus envelope protein 2 ectodomain Journal of virology 2014 ;88(18):10280-10288
Barretto,N.; Sainz,B.,Jr; Hussain,S.; Uprichard,S. L.Determining the involvement and therapeutic implications of host cellular factors in hepatitis C virus cell-to-cell spread Journal of virology 2014 ;88(9):5050-5061
Guedj,J.; Dahari,H.; Rong,L.; Sansone,N. D.; Nettles,R. E.; Cotler,S. J.; Layden,T. J.; Uprichard,S. L.; Perelson,A. S.Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life Proceedings of the National Academy of Sciences of the United States of America 2013 ;110(10):3991-3996
Guedj,J.; Dahari,H.; Uprichard,S. L.; Perelson,A. S.The hepatitis C virus NS5A inhibitor daclatasvir has a dual mode of action and leads to a new virus half-life estimate Expert review of gastroenterology & hepatology 2013 ;7(5):397-399
Martin,D. N.; Uprichard,S. L.Identification of transferrin receptor 1 as a hepatitis C virus entry factor Proceedings of the National Academy of Sciences of the United States of America 2013 ;110(26):10777-10782
Lee,H.; Zhu,T.; Patel,K.; Zhang,Y. Y.; Truong,L.; Hevener,K. E.; Gatuz,J. L.; Subramanya,G.; Jeong,H. Y.; Uprichard,S. L.; Johnson,M. E.High-throughput screening (HTS) and hit validation to identify small molecule inhibitors with activity against NS3/4A proteases from multiple hepatitis C virus genotypes PLoS ONE 2013 ;8(10):e75144
Sainz,B.,Jr; Barretto,N.; Martin,D. N.; Hiraga,N.; Imamura,M.; Hussain,S.; Marsh,K. A.; Yu,X.; Chayama,K.; Alrefai,W. A.; Uprichard,S. L.Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor Nature medicine 2012 ;18(2):281-285
Sainz,B.,Jr; Barretto,N.; Yu,X.; Corcoran,P.; Uprichard,S. L.Permissiveness of human hepatoma cell lines for HCV infection Virology Journal 2012 ;9:30-422X-9-30
Yu,X.; Sainz,B.,Jr; Petukhov,P. A.; Uprichard,S. L.Identification of hepatitis C virus inhibitors targeting different aspects of infection using a cell-based assay Antimicrobial Agents and Chemotherapy 2012 ;56(12):6109-6120
Hussain,S.; Barretto,N.; Uprichard,S. L.New hepatitis C virus drug discovery strategies and model systems Expert opinion on drug discovery 2012 ;7(9):849-859
Tencate,V.; Sainz,B.,Jr; Cotler,S. J.; Uprichard,S. L.Potential treatment options and future research to increase hepatitis C virus treatment response rate Hepatic medicine : evidence and research 2010 ;2010(2):125-145
Cobleigh,M. A.; Buonocore,L.; Uprichard,S. L.; Rose,J. K.; Robek,M. D.A vesicular stomatitis virus-based hepatitis B virus vaccine vector provides protection against challenge in a single dose Journal of virology 2010 ;84(15):7513-7522
Uprichard,S. L.Hepatitis C virus experimental model systems and antiviral drug research Virologica Sinica 2010 ;25(4):227-245
Sabahi,A.; Marsh,K. A.; Dahari,H.; Corcoran,P.; Lamora,J. M.; Yu,X.; Garry,R. F.; Uprichard,S. L.The rate of hepatitis C virus infection initiation in vitro is directly related to particle density Virology 2010 ;407(1):110-119
Yu,X.; Uprichard,S. L.Cell-based hepatitis C virus infection fluorescence resonance energy transfer (FRET) assay for antiviral compound screening Current protocols in microbiology 2010 ;Chapter 17:Unit 17.5.
Choi,S.; Sainz,B.,Jr; Corcoran,P.; Uprichard,S.; Jeong,H.Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cells Xenobiotica; the fate of foreign compounds in biological systems 2009 ;39(3):205-217
Sainz,B.,Jr; Barretto,N.; Uprichard,S. L.Hepatitis C virus infection in phenotypically distinct Huh7 cell lines PLoS ONE 2009 ;4(8):e6561
Sainz,B.,Jr; TenCate,V.; Uprichard,S. L.Three-dimensional Huh7 cell culture system for the study of Hepatitis C virus infection Virology Journal 2009 ;6:103-422X-6-103
Li,L.; Oropeza,C. E.; Sainz,B.,Jr; Uprichard,S. L.; Gonzalez,F. J.; McLachlan,A.Developmental regulation of hepatitis B virus biosynthesis by hepatocyte nuclear factor 4alpha PLoS ONE 2009 ;4(5):e5489
Dahari,H.; Sainz,B.,Jr; Perelson,A. S.; Uprichard,S. L.Modeling subgenomic hepatitis C virus RNA kinetics during treatment with alpha interferon Journal of virology 2009 ;83(13):6383-6390
Yu,X.; Sainz,B.,Jr; Uprichard,S. L.Development of a cell-based hepatitis C virus infection fluorescent resonance energy transfer assay for high-throughput antiviral compound screening Antimicrobial Agents and Chemotherapy 2009 ;53(10):4311-4319
Rothwangl,K. B.; Manicassamy,B.; Uprichard,S. L.; Rong,L.Dissecting the role of putative CD81 binding regions of E2 in mediating HCV entry: putative CD81 binding region 1 is not involved in CD81 binding Virology Journal 2008 ;5:46-422X-5-46
Uprichard,S. L.; Chung,J.; Chisari,F. V.; Wakita,T.Replication of a hepatitis C virus replicon clone in mouse cells Virology Journal 2006 ;3:89
Zhong,J.; Gastaminza,P.; Cheng,G.; Kapadia,S.; Kato,T.; Burton,D. R.; Wieland,S. F.; Uprichard,S. L.; Wakita,T.; Chisari,F. V.Robust hepatitis C virus infection in vitro Proceedings of the National Academy of Sciences of the United States of America 2005 ;102(26):9294-9299
Uprichard,S. L.The therapeutic potential of RNA interference FEBS letters 2005 ;579(26):5996-6007
Uprichard,S. L.; Boyd,B.; Althage,A.; Chisari,F. V.Clearance of hepatitis B virus from the liver of transgenic mice by short hairpin RNAs Proceedings of the National Academy of Sciences of the United States of America 2005 ;102(3):773-778
Uprichard,S. L.; Knipe,D. M.Conformational changes in the herpes simplex virus ICP8 DNA-binding protein coincident with assembly in viral replication structures Journal of virology 2003 ;77(13):7467-7476
Uprichard,S. L.; Wieland,S. F.; Althage,A.; Chisari,F. V.Transcriptional and posttranscriptional control of hepatitis B virus gene expression Proceedings of the National Academy of Sciences of the United States of America 2003 ;100(3):1310-1315
Pasquetto,V.; Wieland,S. F.; Uprichard,S. L.; Tripodi,M.; Chisari,F. V.Cytokine-sensitive replication of hepatitis B virus in immortalized mouse hepatocyte cultures Journal of virology 2002 ;76(11):5646-5653