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Susan L. Uprichard Photo
Name
Susan L. Uprichard
Degree
Ph.D.
Rank
Professor
Primary Department
Medicine
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 system’ (2) Characterization of the humanized chimeric mouse model of HBV infection’ (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
Publications
Feng, S; Ali, MS; Evdokimova, M; Reid, GE; Clark, NM; Uprichard, SL; Baker, SC Sequencing during Times of Change: Evaluating SARS-CoV-2 Clinical Samples during the Transition from the Delta to Omicron Wave. Viruses ; 14 7
Uprichard, SL; O'Brien, A; Evdokimova, M; Rowe, CL; Joyce, C; Hackbart, M; Cruz-Pulido, YE; Cohen, CA; Rock, ML; Dye, JM; Kuehnert, P; Ricks, KM; Casper, M; Linhart, L; Anderson, K; Kirk, L; Maggiore, JA; Herbert, AS; Clark, NM; Reid, GE; Baker, SC Antibody Response to SARS-CoV-2 Infection and Vaccination in COVID-19-naïve and Experienced Individuals. Viruses ; 14 2
Shekhtman, L; Navasa, M; Sansone, N; Crespo, G; Subramanya, G; Chung, TL; Cardozo-Ojeda, EF; Pérez-Del-Pulgar, S; Perelson, AS; Cotler, SJ; Forns, X; Uprichard, SL; Dahari, H Modeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance. eLife ; 10
Deng, X; Evdokimova, M; O'Brien, A; Rowe, CL; Clark, NM; Harrington, A; Reid, GE; Uprichard, SL; Baker, SC Breakthrough Infections with Multiple Lineages of SARS-CoV-2 Variants Reveals Continued Risk of Severe Disease in Immunosuppressed Patients. Viruses ; 13 9
Durso-Cain, K; Kumberger, P; Schälte, Y; Fink, T; Dahari, H; Hasenauer, J; Uprichard, SL; Graw, F HCV Spread Kinetics Reveal Varying Contributions of Transmission Modes to Infection Dynamics. Viruses ; 13 7
Reinharz, V; Ishida, Y; Tsuge, M; Durso-Cain, K; Chung, TL; Tateno, C; Perelson, AS; Uprichard, SL; Chayama, K; Dahari, H Understanding hepatitis B virus dynamics and the antiviral effect of interferon-a treatment in humanized chimeric mice. Journal of virology ;
Dasgupta, Swikriti; Imamura, Michio; Gorstein, Evan; Nakahara, Takashi; Tsuge, Masataka; Churkin, Alexander; Yardeni, David; Etzion, Ohad; Uprichard, Susan L; Barash, Danny; Cotler, Scott J; Dahari, Harel; Chayama, Kazuaki Modeling-Based Response-Guided Glecaprevir-Pibrentasvir Therapy for Chronic Hepatitis C to Identify Patients for Ultrashort Treatment Duration. Journal of Infectious Diseases ; 222 7
Etzion, O; Dahari, H; Yardeni, D; Issachar, A; Nevo-Shor, A; Cohen-Naftaly, M; Ashur, Y; Uprichard, SL; Arbib, OS; Munteanu, D; Braun, M; Cotler, SJ; Abufreha, N; Keren-Naus, A; Shemer-Avni, Y; Mor, O; Murad, J; Novack, V; Shlomai, A Response guided therapy for reducing duration of direct acting antivirals in chronic hepatitis C infected patients: a Pilot study. Scientific reports ; 10 1
Dasgupta, S; Imamura, M; Gorstein, E; Nakahara, T; Tsuge, M; Churkin, A; Yardeni, D; Etzion, O; Uprichard, SL; Barash, D; Cotler, SJ; Dahari, H; Chayama, K Modeling-based response-guided therapy for chronic hepatitis C under glecaprevir/pibrentasvir may identify patients for ultra-short treatment duration. The Journal of infectious diseases ;
Shekhtman, L; Cotler, SJ; Hershkovich, L; Uprichard, SL; Bazinet, M; Pantea, V; Cebotarescu, V; Cojuhari, L; Jimbei, P; Krawczyk, A; Dittmer, U; Vaillant, A; Dahari, H Modelling hepatitis D virus RNA and HBsAg dynamics during nucleic acid polymer monotherapy suggest rapid turnover of HBsAg. Scientific reports ; 10 1
Gorstein, E; Martinello, M; Churkin, A; Dasgupta, S; Walsh, K; Applegate, TL; Yardeni, D; Etzion, O; Uprichard, SL; Barash, D; Cotler, SJ; Matthews, GV; Dahari, H Modeling based response guided therapy in subjects with recent hepatitis C infection. Antiviral Research ; 180
Koh, C; Dubey, P; Han, MAT; Walter, PJ; Garraffo, HM; Surana, P; Southall, NT; Borochov, N; Uprichard, SL; Cotler, SJ; Etzion, O; Heller, T; Dahari, H; Liang, TJ A randomized, proof-of-concept clinical trial on repurposing chlorcyclizine for the treatment of chronic hepatitis C. Antiviral Research ; 163
Tsuge, M; Uchida, T; Walsh, K; Ishida, Y; Tateno, C; Kumar, U; Glenn, JS; Koh, C; Heller, T; Uprichard, SL; Dahari, H; Chayama, K Early Multiphasic HBV Infection Initiation Kinetics Is Not Clone-Specific and Is Not Affected by Hepatitis D Virus (HDV) Infection. Viruses ; 11 3
Gambato, M; Canini, L; Lens, S; Graw, F; Perpiñan, E; Londoño, MC; Uprichard, SL; Mariño, Z; Reverter, E; Bartres, C; González, P; Pla, A; Costa, J; Burra, P; Cotler, SJ; Forns, X; Dahari, H Early HCV viral kinetics under DAAs may optimize duration of therapy in patients with compensated cirrhosis. Liver international : official journal of the International Association for the Study of the Liver ; 39 5
Kumberger, P; Durso-Cain, K; Uprichard, SL; Dahari, H; Graw, F Accounting for Space—Quantification of Cell-To-Cell Transmission Kinetics Using Virus Dynamics Models. Viruses ; 10 4
Hasin Y, Shteingart S, Dahari H, Gafanovich I, Floru S, Braun M, Shlomai A, Verstandig A, Dery I, Uprichard SL, Cotler SJ, Lurie Y Hepatitis C virus cures after direct acting antiviral-related drug-induced liver injury WORLD JOURNAL OF HEPATOLOGY ; 8 20 858-862
Koh, Christopher; Canini, Laetitia; Dahari, Harel; Zhao, Xiongce; Uprichard, Susan L; Haynes-Williams, Vanessa; Winters, Mark A; Subramanya, Gitanjali; Cooper, Stewart L; Pinto, Peter; Wolff, Erin F; Bishop, Rachel; Ai Thanda Han, Ma; Cotler, Scott J; Kleiner, David E; Keskin, Onur; Idilman, Ramazan; Yurdaydin, Cihan; Glenn, Jeffrey S; Heller, Theo Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial. LANCET INFECTIOUS DISEASES ; 15 10
Barretto, N; Uprichard, SL Hepatitis C virus Cell-to-cell Spread Assay. Bio-protocol ; 4 24