Susan L. Uprichard, PhD

Medicine

Hepatology
Microbiology and Immunology
Associate Professor
Director of Research, Hepatology

Languages Spoken

English

Research

  • HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir simeprevir or ledipasvir, 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., Journal of Hepatology
  • Inhibition of hepatitis C entry: too soon to dismiss while many are still being denied treatment Uprichard, S. L.; Sainz, B., Jr, Gut
  • Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised double-blind, placebo-controlled phase 2A trial, 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., The Lancet.Infectious diseases
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  • Quantification of Hepatitis C Virus Cell-to-Cell Spread Using a Stochastic Modeling Approach Graw, F.; Martin, D. N.; Perelson, A. S.; Uprichard, S. L.; Dahari, H., Journal of virology
  • Determining the involvement and therapeutic implications of host cellular factors in hepatitis C virus cell-to-cell spread Barretto, N.; Sainz, B., Jr; Hussain, S.; Uprichard, S. L., Journal of virology
  • Establishment of mice with inheritable susceptibility to productive hepatitis C virus infection Uprichard, S. L., Hepatology (Baltimore, Md.)
  • Minireview: Unexpected structural features of the hepatitis c virus envelope protein 2 ectodomain Sabahi, A.; Uprichard, S. L.; Wimley, W. C.; Dash, S.; Garry, R. F., Journal of virology
  • Unexpected structural features of the hepatitis C virus envelope protein 2 ectodomain Sabahi, A.; Uprichard, S. L.; Wimley, W. C.; Dash, S.; Garry, R. F., Journal of virology
  • High-throughput screening (HTS) and hit validation to identify small molecule inhibitors with activity against NS3/4A proteases from multiple hepatitis C virus genotypes 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., PLoS ONE
  • Identification of transferrin receptor 1 as a hepatitis C virus entry factor Martin, D. N.; Uprichard, S. L., Proceedings of the National Academy of Sciences of the United States of America
  • Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life Guedj, 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
  • The hepatitis C virus NS5A inhibitor daclatasvir has a dual mode of action and leads to a new virus half-life estimate Guedj, J.; Dahari, H.; Uprichard, S. L.; Perelson, A. S., Expert review of gastroenterology & hepatology
  • Identification of hepatitis C virus inhibitors targeting different aspects of infection using a cell-based assay Yu, X.; Sainz, B., Jr; Petukhov, P. A.; Uprichard, S. L., Antimicrobial Agents and Chemotherapy
  • Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor 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., Nature medicine
  • New hepatitis C virus drug discovery strategies and model systems Hussain, S.; Barretto, N.; Uprichard, S. L., Expert opinion on drug discovery
  • Permissiveness of human hepatoma cell lines for HCV infection Sainz, B., Jr; Barretto, N.; Yu, X.; Corcoran, P.; Uprichard, S. L., Virology Journal
  • A vesicular stomatitis virus-based hepatitis B virus vaccine vector provides protection against challenge in a single dose Cobleigh, M. A.; Buonocore, L.; Uprichard, S. L.; Rose, J. K.; Robek, M. D., Journal of virology
  • Cell-based hepatitis C virus infection fluorescence resonance energy transfer (FRET) assay for antiviral compound screening Yu, X.; Uprichard, S. L., Current protocols in microbiology
  • Hepatitis C virus experimental model systems and antiviral drug research Uprichard, S. L., Virologica Sinica
  • Potential treatment options and future research to increase hepatitis C virus treatment response rate Tencate, V.; Sainz, B., Jr; Cotler, S. J.; Uprichard, S. L., Hepatic medicine : evidence and research
  • The rate of hepatitis C virus infection initiation in vitro is directly related to particle density Sabahi, A.; Marsh, K. A.; Dahari, H.; Corcoran, P.; Lamora, J. M.; Yu, X.; Garry, R. F.; Uprichard, S. L., Virology
  • Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cells Choi, S.; Sainz, B., Jr; Corcoran, P.; Uprichard, S.; Jeong, H., Xenobiotica; the fate of foreign compounds in biological systems
  • Development of a cell-based hepatitis C virus infection fluorescent resonance energy transfer assay for high-throughput antiviral compound screening Yu, X.; Sainz, B., Jr; Uprichard, S. L., Antimicrobial Agents and Chemotherapy
  • Developmental regulation of hepatitis B virus biosynthesis by hepatocyte nuclear factor 4alpha Li, L.; Oropeza, C. E.; Sainz, B., Jr; Uprichard, S. L.; Gonzalez, F. J.; McLachlan, A., PLoS ONE
  • Hepatitis C virus infection in phenotypically distinct Huh7 cell lines Sainz, B., Jr; Barretto, N.; Uprichard, S. L., PLoS ONE
  • Modeling subgenomic hepatitis C virus RNA kinetics during treatment with alpha interferon Dahari, H.; Sainz, B., Jr; Perelson, A. S.; Uprichard, S. L., Journal of virology
  • Three-dimensional Huh7 cell culture system for the study of Hepatitis C virus infection Sainz, B., Jr; TenCate, V.; Uprichard, S. L., Virology Journal
  • 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 Rothwangl, K. B.; Manicassamy, B.; Uprichard, S. L.; Rong, L., Virology Journal
  • Replication of a hepatitis C virus replicon clone in mouse cells Uprichard, S. L.; Chung, J.; Chisari, F. V.; Wakita, T., Virology Journal
  • Clearance of hepatitis B virus from the liver of transgenic mice by short hairpin RNAs Uprichard, S. L.; Boyd, B.; Althage, A.; Chisari, F. V., Proceedings of the National Academy of Sciences of the United States of America
  • Robust hepatitis C virus infection in vitro Zhong, 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
  • The therapeutic potential of RNA interference Uprichard, S. L., FEBS letters
  • Conformational changes in the herpes simplex virus ICP8 DNA-binding protein coincident with assembly in viral replication structures Uprichard, S. L.; Knipe, D. M., Journal of virology
  • Transcriptional and posttranscriptional control of hepatitis B virus gene expression Uprichard, S. L.; Wieland, S. F.; Althage, A.; Chisari, F. V., Proceedings of the National Academy of Sciences of the United States of America
  • Cytokine-sensitive replication of hepatitis B virus in immortalized mouse hepatocyte cultures Pasquetto, V.; Wieland, S. F.; Uprichard, S. L.; Tripodi, M.; Chisari, F. V., Journal of virology

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.