Susan L. Uprichard
  • Associate Professor
  • Director of Research, Hepatology
  • Hepatology
  • Microbiology and Immunology
Research Keywords
  • Hepatitis
  • Infectious Diseases/Agents
  • Mathematical Modeling
  • Molecular Microbiology
Research Summary

The primary focus of our viral hepatitis research program is hepatitis C virus (HCV). Although HCV infects more than 2% of the world population and represents a significant public health burden, research efforts to understand HCV 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 life cycle, understand molecular mechanisms of HCV-associated liver disease, and identify the viral-host interactions that determine the outcome of infection.

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.


Inhibition of hepatitis C entry: too soon to dismiss while many are still being denied treatmentUprichard,S. L.; Sainz,B.Gut 2014 ; ( ):

Minireview: Unexpected structural features of the hepatitis c virus envelope protein 2 ectodomainSabahi,A.; Uprichard,S. L.; Wimley,W. C.; Dash,S.; Garry,R. F.Journal of virology 2014 ; ( ):

Identification of transferrin receptor 1 as a hepatitis C virus entry factorMartin,D. N.; Uprichard,S. L.Proceedings of the National Academy of Sciences of the United States of America 2013 ;110(26):10777-10782

Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-lifeGuedj,J.; Dahari,H.; Rong,L.; Sansone,N. D.; Nettles,R. E.; Cotler,S. J.; Layden,T. J.; Uprichard,S. L.; Perelson,A. S.Proceedings of the National Academy of Sciences of the United States of America 2013 ;110(10):3991-3996

Establishment of mice with Inheritable susceptibility to productive HCV infectionUprichard,S. L.Hepatology (Baltimore, Md.) 2013 ; ( ):

New hepatitis C virus drug discovery strategies and model systemsHussain,S.; Barretto,N.; Uprichard,S. L.Expert opinion on drug discovery 2012 ;7(9):849-859

Identification of hepatitis C virus inhibitors targeting different aspects of infection using a cell-based assayYu,X.; Sainz,B.,Jr; Petukhov,P. A.; Uprichard,S. L.Antimicrobial Agents and Chemotherapy 2012 ;56(12):6109-6120

Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factorSainz,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.Nature medicine 2012 ;18(2):281-285

Permissiveness of human hepatoma cell lines for HCV infectionSainz,B.,Jr; Barretto,N.; Yu,X.; Corcoran,P.; Uprichard,S. L.Virology Journal 2012 ;9( ):30-422X-9-30

Potential treatment options and future research to increase hepatitis C virus treatment response rateTencate,V.; Sainz,B.,Jr; Cotler,S. J.; Uprichard,S. L.Hepatic medicine : evidence and research 2010 ;2010(2):125-145

Hepatitis C virus experimental model systems and antiviral drug researchUprichard,S. L.Virologica Sinica 2010 ;25(4):227-245

The rate of hepatitis C virus infection initiation in vitro is directly related to particle densitySabahi,A.; Marsh,K. A.; Dahari,H.; Corcoran,P.; Lamora,J. M.; Yu,X.; Garry,R. F.; Uprichard,S. L.Virology 2010 ;407(1):110-119

A vesicular stomatitis virus-based hepatitis B virus vaccine vector provides protection against challenge in a single doseCobleigh,M. A.; Buonocore,L.; Uprichard,S. L.; Rose,J. K.; Robek,M. D.Journal of virology 2010 ;84(15):7513-7522

Cell-based hepatitis C virus infection fluorescence resonance energy transfer (FRET) assay for antiviral compound screeningYu,X.; Uprichard,S. L.Current protocols in microbiology 2010 ;Chapter 17( ):Unit 17.5.

Hepatitis C virus infection in phenotypically distinct Huh7 cell linesSainz,B.,Jr; Barretto,N.; Uprichard,S. L.PLoS ONE 2009 ;4(8):e6561

Three-dimensional Huh7 cell culture system for the study of Hepatitis C virus infectionSainz,B.,Jr; TenCate,V.; Uprichard,S. L.Virology Journal 2009 ;6( ):103-422X-6-103

Development of a cell-based hepatitis C virus infection fluorescent resonance energy transfer assay for high-throughput antiviral compound screeningYu,X.; Sainz,B.,Jr; Uprichard,S. L.Antimicrobial Agents and Chemotherapy 2009 ;53(10):4311-4319

Modeling subgenomic hepatitis C virus RNA kinetics during treatment with alpha interferonDahari,H.; Sainz,B.,Jr; Perelson,A. S.; Uprichard,S. L.Journal of virology 2009 ;83(13):6383-6390

Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cellsChoi,S.; Sainz,B.,Jr; Corcoran,P.; Uprichard,S.; Jeong,H.Xenobiotica; the fate of foreign compounds in biological systems 2009 ;39(3):205-217

Developmental regulation of hepatitis B virus biosynthesis by hepatocyte nuclear factor 4alphaLi,L.; Oropeza,C. E.; Sainz,B.,Jr; Uprichard,S. L.; Gonzalez,F. J.; McLachlan,A.PLoS ONE 2009 ;4(5):e5489

Dissecting the role of putative CD81 binding regions of E2 in mediating HCV entry: putative CD81 binding region 1 is not involved in CD81 bindingRothwangl,K. B.; Manicassamy,B.; Uprichard,S. L.; Rong,L.Virology Journal 2008 ;5( ):46-422X-5-46

Replication of a hepatitis C virus replicon clone in mouse cellsUprichard,S. L.; Chung,J.; Chisari,F. V.; Wakita,T.Virology Journal 2006 ;3( ):89

Robust hepatitis C virus infection in vitroZhong,J.; Gastaminza,P.; Cheng,G.; Kapadia,S.; Kato,T.; Burton,D. R.; Wieland,S. F.; Uprichard,S. L.; Wakita,T.; Chisari,F. V.Proceedings of the National Academy of Sciences of the United States of America 2005 ;102(26):9294-9299

The therapeutic potential of RNA interferenceUprichard,S. L.FEBS letters 2005 ;579(26):5996-6007

Clearance of hepatitis B virus from the liver of transgenic mice by short hairpin RNAsUprichard,S. L.; Boyd,B.; Althage,A.; Chisari,F. V.Proceedings of the National Academy of Sciences of the United States of America 2005 ;102(3):773-778

Conformational changes in the herpes simplex virus ICP8 DNA-binding protein coincident with assembly in viral replication structuresUprichard,S. L.; Knipe,D. M.Journal of virology 2003 ;77(13):7467-7476

Transcriptional and posttranscriptional control of hepatitis B virus gene expressionUprichard,S. L.; Wieland,S. F.; Althage,A.; Chisari,F. V.Proceedings of the National Academy of Sciences of the United States of America 2003 ;100(3):1310-1315

Cytokine-sensitive replication of hepatitis B virus in immortalized mouse hepatocyte culturesPasquetto,V.; Wieland,S. F.; Uprichard,S. L.; Tripodi,M.; Chisari,F. V.Journal of virology 2002 ;76(11):5646-5653