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About Ruldolf K. Beran, Ph.D.

Senior Research Scientist II, Discovery Virology

Ph: (650) 522-1660

Email: rudolf.beran@gilead.com

 

Training

(2003-2009) Post-doctoral fellow (recipient of NIH and Gilead fellowships), Biochemistry, Yale University.  Mentored jointly by  Dr. Anna Marie Pyle and Dr. Brett Lindenbach                             

(1997- 2003) Ph.D., Microbiology, University of California, Los Angeles. Mentored by Dr. Robert W. Simons.                                   

(1993-1997) B.S., Biochemistry and Cell Biology, University of California, San Diego.

 

Work Experience

Senior Research Scientist II (Gilead Sciences, Foster City, CA) (2020 - present):

Pursuing immunomodulatory HBV curative strategies through WHV-infected woodchuck efficacy studies. Continuing to study the interplay between HBx and the Smc5/6 complex (see below).

Senior Research Scientist I (Gilead Sciences, Foster City, CA) (2012 - 2020):

  • Serving as the core biologist on the HBx inhibitor team since July 2013.
  • Working on characterizing HBx and Smc5/6 function.
  • Demonstrated leadership in the HBx field: 
    • Recent research publications include the Nature paper that identified and characterized HBx function, a PlosOne paper that identified the interactions between HBx, Smc5/6, and Nuclear Domain 10, a Journal of Virology paper that identified an HBx zinc-binding motif, and a last-author Journal of Virology paper that characterized HBx expression, stability, and localization during HBV infection of primary human hepatocytes as well as the potential for Smc5/6 reappearance during inhibition of HBx function.
  • Published a last-author HBx review for the journal Viruses.
  • HBV talks: HBV 2016 Seoul, SK; EASL 2017 Amsterdam, NL; ANRS 2017 in Paris, FR; HBV 2018 Taormina, ITL; Institute of Organic Chemistry & Biochemistry 2019 Prague, CZ.
  • HBV posters: AASLD 2016, Boston, MA; EASL 2017 Amsterdam, NL; EASL 2018 Paris, FR.

     Research Scientist (Gilead Sciences, Foster City, CA) (2009-2011):                                                                                          

  • Collected HCV resistance data and wrote a chapter of the NS5A inhibitor GS-5816 IND; wrote the biology section for the NS5A inhibitor GS-5800 RFD
  • Served as the core biologist on the HCV Entry Inhibitor team and on the NS5A GS-5800 team.
  • Discovered and characterized the HCV Entry Inhibitor team’s lead compound series from a Gilead high-throughput screen.
  • Determined that the HCV Entry Inhibitor team’s lead compound series was a class of HCV infectivity inhibitors and published a last-author paper on this topic.
  • Published 5 papers and presented 6 conference posters concerning my HCV work at Gilead

Reports

Recommendation for Development (RFDs):

Project: GS-5800 (an HCV NS5A inhibitor), wrote the biology section (2012). 

Investigational New Drug Reports (INDs):

Beran, R.K., Bush, C.O., Yu, M., Gong, R., and Cheng, G.  In Vitro Selection and Characterization of Resistance to GS-5816 in HCV Genotype 1a and 1b Replicon Cells.  June 29, 2012, Report No. PC-281-2013.

 

Published Papers

Kornyeyev, D., Ramakrishnan, D., Voitenleitner, C., Livingston, C.M., Xing, W., Hung, M., Kwon, H., Fletcher, S.P., and Beran, R.K. Spatiotemporal Analysis of Hepatitis B Virus X Protein in Primary Human Hepatocytes. J Virol 2019.

Ramakrishnan, D., Xing, W., Beran, R.K., Chemuru, S., Rohrs, H., Niedziela-Majka, A., Marchand, B., Mehra, U., Zábranský, A., Doležal, M., Hubálek, M., Pichová, I., Gross, M.L., Kwon, H., and Fletcher, S.P. Hepatitis B Virus X Protein Function Requires Zinc Binding. J Virol 2019.

Dvory-Sobol, H., Han, B., Lu, J., Yu, M., Beran, R.K., Cheng, G., Martin, R., Svarovskaia, E., Mo, H. In Vitro Resistance Profile of Hepatitis C Virus NS5A Inhibitor Velpatasvir in Genotypes 1 to 6. J Virol Hep 2019.

Niu, C., Li, L., Daffis, S., Lucifora, J., Bonnin, M., Maadadi, S., Salas, E., Chu, R., Ramos, H., Livingston, C.M., Beran, R.K., Garg, A.V., Balsitis, S., Durantel, D., Zoulim, F., Delaney, W.E. 4th, and Fletcher, S.P.  Toll-Like Receptor 7 Agonist GS-9620 Induces Prolonged Inhibition of HBV via a Type I Interferon-Dependent Mechanism.  J Hepatol 2017, (17):32489-3.

Livingston, C.M., Ramakrishnan, D., Strubin, M., Fletcher, S.P., and Beran, R.K. Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6.  Viruses  2017 Apr 3; 9(4).

Niu, C.*, Livingston, C.M.*, Li, L.*, Beran, R.K*., Daffis, S., Ramakrishnan, D., Burdette, D., Peiser, L., Salas, E., Ramos, H., Yu, M., Cheng, G. Strubin, M., Delaney, W.E., and Fletcher, S.P.  The Smc5/6 Complex Restricts HBV when Localized to ND10 without Inducing an Innate Immune Response and is Counteracted by the HBV X Protein Shortly after Infection.  PLoS One 2017.  (* shared first authorship).

Decorsiere, A., Mueller, H., van Breugel, P.C., Abdul, F., Gerossier, L., Beran, R.K., Livingston, C.M., Niu, C., Fletcher, S.P., Hantz, O., and Strubin, M. Hepatitis B Virus X Protein Identifies the Smc5/6 Complex as a Viral Restriction Factor.  Nature 2016.

Bush, C.O., Pokrovskii, M.V., Saito,R., Morganelli, P., Canales, E., Clarke, M.O., Lazerwith, S.E., Golde, J., Reid, B.G., Babaoglu, K., Pagratis, N., Zhong, W., Delaney IV, W.E., Paulson, M.S., and Beran, R.K. A Small Molecule Inhibitor of Hepatitis C Viral Infectivity.  Antimicrobial Agents & Chemotherapy 2014, 58(1): 386-96.

Bush, C.O., Greenstein, A.E., Delaney IV, W.E., and Beran, R.K.  Hepatitis C Viral Entry Inhibitors Promote a Prolonged Viral Suppression by Replication Inhibitors in Persistently-Infected Huh7 Cultures.  PLoS One  2013, 8(6): e65273.

Beran, R.K., Sharma, R., Corsa, A.C., Tian, Y., Golde, J., Lundgaard, G, Delaney IV, W.E., Zhong, W., and Greenstein, A.E.  The Hsp90 Inhibitor 17-AAG Inhibits Hepatitis C Viral Replication through Cytostasis. PLoS One 2012, 7(2): e30286.

Chan, K., Cheng, G. Beran, R.K., Yang, H., Appleby, T., Pokrovskii, M., Mo, H., Delaney IV, W., and Zhong, W.  An Adaptive Mutation in NS2 is Essential for Efficient Production of Infectious 1b/2a Chimeric Hepatitis C Virus in Cell Culture. Virology 2012, 422: 224-234.

Pokrovskii, M.V., Bush, C.O., Beran, R.K., Robinson, M.F., Cheng, G., Zhong, W., Delaney IV, W.E., and Paulson, M.S.  Novel Mutations in a Tissue-Culture Adapted HCV Strain Improve Infectious Virus Stability and Markedly Enhance Infection Kinetics. J Virol. 2011, 85(8): 3978-3985.

Phan, T., Beran, R.K., Peters, C., Lorenz, I.C., and Lindenbach, B.D.  Hepatitis C virus NS2 protein contributes to virus particle assembly via opposing epistatic interactions with the E1-E2 glycoprotein and NS3-NS4A enzyme complexes.  J Virol. 2009, 83(17): 8379-95.

Beran, R.K., Lindenbach, B.D., and Pyle, A.M.  The NS4A Protein from Hepatitis C Virus Promotes RNA-coupled ATP Hydrolysis by the NS3 Helicase.  J Virol. 2009, 83(7): 3268-75.

Serebrov, V., Beran, R.K., Pyle, A.M.  Establishing a mechanistic basis for the large kinetic steps of the NS3 helicase.  J Biol Chem 2008, 284(4): 2512-21.

Beran, R.K. and Pyle, A.M.  Hepatitis C Viral NS3-4A Protease Activity is Enhanced by the NS3 Helicase. J Biol Chem 2008, 283(44): 29929-37.

Beran, R.K., Serebrov, V., and Pyle, A.M.  The serine protease domain of hepatitis C viral NS3 activates RNA helicase activity by promoting the binding of RNA substrate. J Biol Chem 2007, 282(48): 34913-20.

Lindenbach, B.D., Pragai, B.M., Montserret, R., Beran, R.K., Pyle, A.M., Penin, F., and Rice, C.M.  The C-terminus of hepatitis C virus NS4A encodes an electrostatic switch that regulates NS5A hyperphosphorylation and viral replication.  J Virol 2007, 81(17): 8905-18.

Beran, R.K., Bruno, M.M., Bowers, H.A., Jankowsky, E., and Pyle A.M. Robust translocation along a molecular monorail: the NS3 helicase from hepatitis C virus traverses unusually large disruptions in its track.  J Mol Biol 2006, 358(4):974-82.

Dumont, S., Cheng, W., Serebrov, V., Beran, R.K., Tinoco, I. Jr., Pyle, A.M., and Bustamante, C.  RNA translocation and unwinding mechanism of HCV NS3 helicase and its coordination by ATP.  Nature 2006, 439(7072):105-8.

Prud'homme Genereux, A., Beran, R.K., Iost, I., Ramey, C.S., Mackie, G.A., and Simons, R.W.  Physical and functional interactions among RNase E, polynucleotide phosphorylase and the cold-shock protein, CsdA: evidence for a 'cold shock degradosome'.  Mol Microbiol 2004; 54(5):1409-21.

Beran, R.K., Prud’homme Genereux, A., Baker, K.E. Miao, X., Simons, R.W., and Mackie, G.A. mRNA decay in Escherichia coli: enzymes, mechanisms, and adaptation.  In Translation Mechanisms.  Brakier-Gingras, L., Lapointe, J. (ed.). Landes Bioscience, 2002, Ch. 9.

Beran, R.K. and Simons, R.W.  Cold-temperature induction of Escherichia coli polynucleotide phosphorylase occurs by reversal of its autoregulation.  Mol Microbiol 2001, 39(1):112-25.

Selected Talks

2019:    Invited speaker/consultant to the Institute of Organic Chemistry and Biochemistry, Prague,

                   Czech Republic. Talk title: “Characterizing Interplay between Hepatitis B Virus X Protein

                   and Smc5/6”.

2018:    International HBV Meeting, Taormina, Italy. Talk title: “Spatiotemporal Analysis of Hepatitis

                   B Virus X Protein (HBx) in HBV-Infected Primary Human Hepatocytes”.

2017:    Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS 2017), Paris,

                   France. Talk title: “Characterizing interplay between Hepatitis B X protein, Smc5/6, and

                   ND10”.

2017:    EASL: The International Liver Congress, Amsterdam, Netherlands. Talk title:  “Hepatitis B

                   Viral X RNA is Present in Cell Culture-Derived Virus Preparations and Plasma from

                   Chronically Infected Patients”

2016:    International HBV Meeting, Yonsei University, Seoul, South Korea. Talk title: “Hepatitis B

                   Viral X RNA is Detected Very Early After Infection of Primary Human Hepatocytes and

                   Prior to the  Expression of the Other HBV Genes”

2011:     Invited speaker at St. Mary’s College, Moraga, CA, seminar title: “Hepatitis C Virus: Where

                    it Lives, How it Replicates, and How it Assembles”

2009:    Invited from Yale to speak at Gilead Sciences, Foster City, CA: 

                    NS3-4A: A finely tuned machine that is required for hepatitis C viral replication and

                    infectivity”

2009:   Invited speaker at University of Washington, Seattle, WA Microbiology

                    departmental seminar series, “NS3-4A: A finely tuned machine that is required for

                    hepatitis C viral replication and infectivity”

2008:    Invited from Yale to speak at Gilead Sciences, Foster City, CA “Regulation of hepatitis C 

                    viral NS3-4A function”

2000:    FASEB Conference for Post-transcriptional Control of Gene Expression, Copper Mountain,

                    CO, seminar title: Cold-temperature reversal of Escherichia coli  polynucleotide

                    phosphorylase translational repression”

 

Selected Posters

2019:    EMBO Structural Maintenance of Chromosomes workshop, Vienna, Austria. Poster title:

                  “Structure-Function Analysis of the Smc5/6 Complex,a Host Restriction Factor Against

                   Hepatitis B Virus”

2018:    EASL: The International Liver Congress, Paris, France. Poster title:  “Inhibition of Hepatitis

                   B Virus X Protein Leads to the Reappearance of the Smc5/6 Complex in HBV-Infected

                   Primary Human Hepatocytes”

2017:    EASL: The International Liver Congress, Amsterdam, Netherlands. Poster title:  “Hepatitis B

                   Viral X RNA is Present in Cell Culture-Derived Virus Preparations and Plasma from

                   Chronically Infected Patients”

2016:    AASLD: The Liver Meeting, Boston, MA.  Poster title: “Hepatitis B Viral X RNA is Detected

                   Very Early After Infection of Primary Human Hepatocytes and Prior to the Expression

                   of the Other HBV Genes”

2013:    Viruses and Cells 2013, Gordon Research Conference, Barga, Italy.  Poster title: “A Novel

                   Small Molecule Multi-Genotypic Inhibitor of Hepatitis C Viral Infectivity” 

2012:     19th International Symposium on Hepatitis C Virus and Related Viruses, Venice, Italy.  Poster

                    title: “Hepatitis C Viral Entry Inhibitors Promote a Sustained Viral Suppression by

                    Replication Inhibitors in Persistently-Infected Huh7 Cultures”

2011:      18th International Symposium on Hepatitis C Virus and Related Viruses, Seattle, WA.  Poster

                    title: “Differential Reduction of Hepatitis C Viral Load by Viral Entry and Replication 

                    Inhibitors in Persistently-Infected Cell Cultures”

2011:     18th International Symposium on Hepatitis C Virus and Related Viruses, Seattle, WA.  Poster

                    title: “Cellular growth kinetics distinguish a Cyclophilin inhibitor from an HSP90

                    inhibitor as a selective inhibitor of hepatitis C virus”

2010:    FASEB Viral Structure and Assembly conference, Saxton River, VT.  Poster title:

                  “Differential Reduction of Hepatitis C Viral Load by Viral Entry and Replication

                   Inhibitors in Persistently- Infected Cell Cultures”

 

Teaching Experience

Winter 2000: Teaching assistant for Advanced Molecular Genetics, Department of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles. Taught two weekly classes with a total of 60 undergraduate students.

Fall 1998: Teaching assistant for Introductory Bacteriology Laboratory, Department of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles. Taught a biweekly class of 30 undergraduate students.

Management And Non-Research Leadership Experience

Managed various research associates at Gilead since 2010. 

Leading the Biology Department's Ergonomic Task Force since 2017 (Gilead). 

Serving as the Biosafety Officer for the Viral Hepatitis group since 2010 (Gilead). 

 

Honors

2019: Gilead Sciences Thanks Award 

2011: Gilead Sciences Thanks Award 

2010: Gilead Sciences Values at Work Award 

2007: Gilead Sciences Molecular Virology Postdoctoral Fellowship Award (3 years of full post-doc

                 Funding while at Yale)

2005: NIH Ruth Kirschstein Career Development Postdoctoral Fellowship Award (2 years of full

                 post-doc funding at Yale)

1999: Edwin Pauley Pre-doctoral Fellowship Award (2 years of full grad student funding at UCLA)

1997: Magna Cum Laude, University of California, San Diego

1997: Phi Beta Kappa, University of California, San Diego

Volunteer Work

2011, 2020: Volunteered to give community talks for non-scientists in the San Francisco Bay Area to raise awareness and understanding of HCV/HBV.

2005-2009: Was a founding member of the Connecticut chapter of the Surfrider Foundation, served as a board member, organized and participated in beach clean-ups, and wrote a grant proposal which was funded by Patagonia to purchase and distribute cigarette-butt holders to Long Island Sound beach-goers.

 

Personal

I’m a native of the San Francisco Bay Area. Besides studying viruses, I enjoy hiking, camping, surfing, and traveling. I also enjoy watching operas, visiting art museums in Europe, and studying foreign languages.

 

Website

https://www.linkedin.com/in/rudolfkfberan/          

 

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