Glenn C. Randall

Research Summary
Our laboratory investigates the roles of virus-host interactions in replication and pathogenesis. We study RNA viruses, including hepatitis C virus, dengue virus, Zika virus, and noroviruses. These are medically important viruses, causing cirrhosis/liver cancer, hemorrhagic fever, birth defects, and severe GI disease, respectively. We have identified ~100 host cofactors of viral replication. We now study the importance of these cellular genes in diverse steps of the viral life cycle, including entry, the regulation of viral protein translation and RNA replication, modulation of cellular lipid metabolism, the establishment of viral replication complexes, the secretion of infectious virus, and control of infection by the innate immune system.
Keywords
hepatitis C virus, dengue virus, virus-host interactions, noroviruses
Education
  • University of Illinois, Urbana, IL, B.S. Microbiology 05/1993
  • The University of Chicago, Chicago, IL, Ph.D. Virology 12/1999
  • Rockefeller University, New York, NY, Postdoc Virology 07/2005
Biosciences Graduate Program Association
Awards & Honors
  • 1993 - 1995 National Research Service Award NIH
  • 2002 - 2005 Postdoctoral Fellow American Cancer Society
  • 2006 - Outstanding New Investigator Award NIH DDRCC
  • 2007 - 2008 Herman Lopata Hepatitis C Liver Scholar American Liver Foundation
  • 2007 - 2009 Career Development Award Schweppe Foundation
  • 2008 - 2011 Career Development Award NIH GLRCE
  • 2010 - 2014 Research Scholar American Cancer Society
  • 2011 - Investigator in the Pathogenesis of Infectious Disease Finalist Burroughs Wellcome Fund
Publications
  1. Zhang Z, He G, Filipowicz NA, Randall G, Belov GA, Kopek BG, Wang X. Host Lipids in Positive-Strand RNA Virus Genome Replication. Front Microbiol. 2019; 10:286. View in: PubMed

  2. Baktash Y, Randall G. Live Cell Imaging of Hepatitis C Virus Trafficking in Hepatocytes. Methods Mol Biol. 2019; 1911:263-274. View in: PubMed

  3. Kincaid RP, Lam VL, Chirayil RP, Randall G, Sullivan CS. RNA triphosphatase DUSP11 enables exonuclease XRN-mediated restriction of hepatitis C virus. Proc Natl Acad Sci U S A. 2018 08 07; 115(32):8197-8202. View in: PubMed

  4. Randall G. Lipid Droplet Metabolism during Dengue Virus Infection. Trends Microbiol. 2018 08; 26(8):640-642. View in: PubMed

  5. Baktash Y, Madhav A, Coller KE, Randall G. Single Particle Imaging of Polarized Hepatoma Organoids upon Hepatitis C Virus Infection Reveals an Ordered and Sequential Entry Process. Cell Host Microbe. 2018 03 14; 23(3):382-394.e5. View in: PubMed

  6. Xiao F, Wang S, Barouch-Bentov R, Neveu G, Pu S, Beer M, Schor S, Kumar S, Nicolaescu V, Lindenbach BD, Randall G, Einav S. Interactions between the Hepatitis C Virus Nonstructural 2 Protein and Host Adaptor Proteins 1 and 4 Orchestrate Virus Release. MBio. 2018 03 13; 9(2). View in: PubMed

  7. Jordan TX, Randall G. Dengue Virus Activates the AMP Kinase-mTOR Axis To Stimulate a Proviral Lipophagy. J Virol. 2017 06 01; 91(11). View in: PubMed

  8. Bekerman E, Neveu G, Shulla A, Brannan J, Pu SY, Wang S, Xiao F, Barouch-Bentov R, Bakken RR, Mateo R, Govero J, Nagamine CM, Diamond MS, De Jonghe S, Herdewijn P, Dye JM, Randall G, Einav S. Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects. J Clin Invest. 2017 Apr 03; 127(4):1338-1352. View in: PubMed

  9. Jordan TX, Randall G. Flavivirus modulation of cellular metabolism. Curr Opin Virol. 2016 08; 19:7-10. View in: PubMed

  10. Shulla A, Randall G. (+) RNA virus replication compartments: a safe home for (most) viral replication. Curr Opin Microbiol. 2016 08; 32:82-88. View in: PubMed

  11. Zhang J, Zhang Z, Chukkapalli V, Nchoutmboube JA, Li J, Randall G, Belov GA, Wang X. Positive-strand RNA viruses stimulate host phosphatidylcholine synthesis at viral replication sites. Proc Natl Acad Sci U S A. 2016 Feb 23; 113(8):E1064-73. View in: PubMed

  12. Perin PM, Haid S, Brown RJ, Doerrbecker J, Schulze K, Zeilinger C, von Schaewen M, Heller B, Vercauteren K, Luxenburger E, Baktash YM, Vondran FW, Speerstra S, Awadh A, Mukhtarov F, Schang LM, Kirschning A, Müller R, Guzman CA, Kaderali L, Randall G, Meuleman P, Ploss A, Pietschmann T. Flunarizine prevents hepatitis C virus membrane fusion in a genotype-dependent manner by targeting the potential fusion peptide within E1. Hepatology. 2016 Jan; 63(1):49-62. View in: PubMed

  13. Shulla A, Randall G. Spatiotemporal analysis of hepatitis C virus infection. PLoS Pathog. 2015 Mar; 11(3):e1004758. View in: PubMed

  14. Chukkapalli V, Berger KL, Kelly SM, Thomas M, Deiters A, Randall G. Daclatasvir inhibits hepatitis C virus NS5A motility and hyper-accumulation of phosphoinositides. Virology. 2015 Feb; 476:168-179. View in: PubMed

  15. Chukkapalli V, Randall G. Hepatitis C virus replication compartment formation: mechanism and drug target. Gastroenterology. 2014 May; 146(5):1164-7. View in: PubMed

  16. Schoggins JW, Randall G. Lipids in innate antiviral defense. Cell Host Microbe. 2013 Oct 16; 14(4):379-85. View in: PubMed

  17. Dolan PT, Zhang C, Khadka S, Arumugaswami V, Vangeloff AD, Heaton NS, Sahasrabudhe S, Randall G, Sun R, LaCount DJ. Identification and comparative analysis of hepatitis C virus-host cell protein interactions. Mol Biosyst. 2013 Dec; 9(12):3199-209. View in: PubMed

  18. Czaja MJ, Ding WX, Donohue TM, Friedman SL, Kim JS, Komatsu M, Lemasters JJ, Lemoine A, Lin JD, Ou JH, Perlmutter DH, Randall G, Ray RB, Tsung A, Yin XM. Functions of autophagy in normal and diseased liver. Autophagy. 2013 Aug; 9(8):1131-58. View in: PubMed

  19. Oakland TE, Haselton KJ, Randall G. EWSR1 binds the hepatitis C virus cis-acting replication element and is required for efficient viral replication. J Virol. 2013 Jun; 87(12):6625-34. View in: PubMed

  20. Shulla A, Randall G. Hepatitis C virus-host interactions, replication, and viral assembly. Curr Opin Virol. 2012 Dec; 2(6):725-32. View in: PubMed

  21. Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA, Ahn HJ, Ait-Mohamed O, Ait-Si-Ali S, Akematsu T, Akira S, Al-Younes HM, Al-Zeer MA, Albert ML, Albin RL, Alegre-Abarrategui J, Aleo MF, Alirezaei M, Almasan A, Almonte-Becerril M, Amano A, Amaravadi R, Amarnath S, Amer AO, Andrieu-Abadie N, Anantharam V, Ann DK, Anoopkumar-Dukie S, Aoki H, Apostolova N, Arancia G, Aris JP, Asanuma K, Asare NY, Ashida H, Askanas V, Askew DS, Auberger P, Baba M, Backues SK, Baehrecke EH, Bahr BA, Bai XY, Bailly Y, Baiocchi R, Baldini G, Balduini W, Ballabio A, Bamber BA, Bampton ET, Bánhegyi G, Bartholomew CR, Bassham DC, Bast RC, Batoko H, Bay BH, Beau I, Béchet DM, Begley TJ, Behl C, Behrends C, Bekri S, Bellaire B, Bendall LJ, Benetti L, Berliocchi L, Bernardi H, Bernassola F, Besteiro S, Bhatia-Kissova I, Bi X, Biard-Piechaczyk M, Blum JS, Boise LH, Bonaldo P, Boone DL, Bornhauser BC, Bortoluci KR, Bossis I, Bost F, Bourquin JP, Boya P, Boyer-Guittaut M, Bozhkov PV, Brady NR, Brancolini C, Brech A, Brenman JE, Brennand A, Bresnick EH, Brest P, Bridges D, Bristol ML, Brookes PS, Brown EJ, Brumell JH, Brunetti-Pierri N, Brunk UT, Bulman DE, Bultman SJ, Bultynck G, Burbulla LF, Bursch W, Butchar JP, Buzgariu W, Bydlowski SP, Cadwell K, Cahová M, Cai D, Cai J, Cai Q, Calabretta B, Calvo-Garrido J, Camougrand N, Campanella M, Campos-Salinas J, Candi E, Cao L, Caplan AB, Carding SR, Cardoso SM, Carew JS, Carlin CR, Carmignac V, Carneiro LA, Carra S, Caruso RA, Casari G, Casas C, Castino R, Cebollero E, Cecconi F, Celli J, Chaachouay H, Chae HJ, Chai CY, Chan DC, Chan EY, Chang RC, Che CM, Chen CC, Chen GC, Chen GQ, Chen M, Chen Q, Chen SS, Chen W, Chen X, Chen X, Chen X, Chen YG, Chen Y, Chen Y, Chen YJ, Chen Z, Cheng A, Cheng CH, Cheng Y, Cheong H, Cheong JH, Cherry S, Chess-Williams R, Cheung ZH, Chevet E, Chiang HL, Chiarelli R, Chiba T, Chin LS, Chiou SH, Chisari FV, Cho CH, Cho DH, Choi AM, Choi D, Choi KS, Choi ME, Chouaib S, Choubey D, Choubey V, Chu CT, Chuang TH, Chueh SH, Chun T, Chwae YJ, Chye ML, Ciarcia R, Ciriolo MR, Clague MJ, Clark RS, Clarke PG, Clarke R, Codogno P, Coller HA, Colombo MI, Comincini S, Condello M, Condorelli F, Cookson MR, Coombs GH, Coppens I, Corbalan R, Cossart P, Costelli P, Costes S, Coto-Montes A, Couve E, Coxon FP, Cregg JM, Crespo JL, Cronjé MJ, Cuervo AM, Cullen JJ, Czaja MJ, D'Amelio M, Darfeuille-Michaud A, Davids LM, Davies FE, De Felici M, de Groot JF, de Haan CA, De Martino L, De Milito A, De Tata V, Debnath J, Degterev A, Dehay B, Delbridge LM, Demarchi F, Deng YZ, Dengjel J, Dent P, Denton D, Deretic V, Desai SD, Devenish RJ, Di Gioacchino M, Di Paolo G, Di Pietro C, Díaz-Araya G, Díaz-Laviada I, Diaz-Meco MT, Diaz-Nido J, Dikic I, Dinesh-Kumar SP, Ding WX, Distelhorst CW, Diwan A, Djavaheri-Mergny M, Dokudovskaya S, Dong Z, Dorsey FC, Dosenko V, Dowling JJ, Doxsey S, Dreux M, Drew ME, Duan Q, Duchosal MA, Duff K, Dugail I, Durbeej M, Duszenko M, Edelstein CL, Edinger AL, Egea G, Eichinger L, Eissa NT, Ekmekcioglu S, El-Deiry WS, Elazar Z, Elgendy M, Ellerby LM, Eng KE, Engelbrecht AM, Engelender S, Erenpreisa J, Escalante R, Esclatine A, Eskelinen EL, Espert L, Espina V, Fan H, Fan J, Fan QW, Fan Z, Fang S, Fang Y, Fanto M, Fanzani A, Farkas T, Farré JC, Faure M, Fechheimer M, Feng CG, Feng J, Feng Q, Feng Y, Fésüs L, Feuer R, Figueiredo-Pereira ME, Fimia GM, Fingar DC, Finkbeiner S, Finkel T, Finley KD, Fiorito F, Fisher EA, Fisher PB, Flajolet M, Florez-McClure ML, Florio S, Fon EA, Fornai F, Fortunato F, Fotedar R, Fowler DH, Fox HS, Franco R, Frankel LB, Fransen M, Fuentes JM, Fueyo J, Fujii J, Fujisaki K, Fujita E, Fukuda M, Furukawa RH, Gaestel M, Gailly P, Gajewska M, Galliot B, Galy V, Ganesh S, Ganetzky B, Ganley IG, Gao FB, Gao GF, Gao J, Garcia L, Garcia-Manero G, Garcia-Marcos M, Garmyn M, Gartel AL, Gatti E, Gautel M, Gawriluk TR, Gegg ME, Geng J, Germain M, Gestwicki JE, Gewirtz DA, Ghavami S, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012 Apr; 8(4):445-544. View in: PubMed

  22. Chukkapalli V, Heaton NS, Randall G. Lipids at the interface of virus-host interactions. Curr Opin Microbiol. 2012 Aug; 15(4):512-8. View in: PubMed

  23. Coller KE, Heaton NS, Berger KL, Cooper JD, Saunders JL, Randall G. Molecular determinants and dynamics of hepatitis C virus secretion. PLoS Pathog. 2012 Jan; 8(1):e1002466. View in: PubMed

  24. Polyak SJ, Morishima C, Scott JD, Gastaminza P, Cox A, de Araújo ES, Higgs MR, Loo YM, Golden-Mason L, Lindenbach BD, Baumert TF, Randall G, Gale M. A summary of the 18th International Symposium on Hepatitis C Virus and Related Viruses. Gastroenterology. 2012 Jan; 142(1):e1-5. View in: PubMed

  25. Jordan TX, Randall G. Manipulation or capitulation: virus interactions with autophagy. Microbes Infect. 2012 Feb; 14(2):126-39. View in: PubMed

  26. Heaton NS, Randall G. Dengue virus and autophagy. Viruses. 2011 08; 3(8):1332-41. View in: PubMed

  27. Berger KL, Randall G. Possibilities for RNA interference in developing hepatitis C virus therapeutics. Viruses. 2010 Aug; 2(8):1647-65. View in: PubMed

  28. Te HS, Randall G, Jensen DM. Mechanism of action of ribavirin in the treatment of chronic hepatitis C. Gastroenterol Hepatol (N Y). 2007 Mar; 3(3):218-25. View in: PubMed

  29. Khadka S, Vangeloff AD, Zhang C, Siddavatam P, Heaton NS, Wang L, Sengupta R, Sahasrabudhe S, Randall G, Gribskov M, Kuhn RJ, Perera R, LaCount DJ. A physical interaction network of dengue virus and human proteins. Mol Cell Proteomics. 2011 Dec; 10(12):M111.012187. View in: PubMed

  30. Berger KL, Kelly SM, Jordan TX, Tartell MA, Randall G. Hepatitis C virus stimulates the phosphatidylinositol 4-kinase III alpha-dependent phosphatidylinositol 4-phosphate production that is essential for its replication. J Virol. 2011 Sep; 85(17):8870-83. View in: PubMed

  31. Heaton NS, Randall G. Multifaceted roles for lipids in viral infection. Trends Microbiol. 2011 Jul; 19(7):368-75. View in: PubMed

  32. Heaton NS, Randall G. Dengue virus-induced autophagy regulates lipid metabolism. Cell Host Microbe. 2010 Nov 18; 8(5):422-32. View in: PubMed

  33. Heaton NS, Perera R, Berger KL, Khadka S, Lacount DJ, Kuhn RJ, Randall G. Dengue virus nonstructural protein 3 redistributes fatty acid synthase to sites of viral replication and increases cellular fatty acid synthesis. Proc Natl Acad Sci U S A. 2010 Oct 05; 107(40):17345-50. View in: PubMed

  34. Berger KL, Randall G. Potential roles for cellular cofactors in hepatitis C virus replication complex formation. Commun Integr Biol. 2009 Nov; 2(6):471-3. View in: PubMed

  35. Coller KE, Berger KL, Heaton NS, Cooper JD, Yoon R, Randall G. RNA interference and single particle tracking analysis of hepatitis C virus endocytosis. PLoS Pathog. 2009 Dec; 5(12):e1000702. View in: PubMed

  36. Berger KL, Cooper JD, Heaton NS, Yoon R, Oakland TE, Jordan TX, Mateu G, Grakoui A, Randall G. Roles for endocytic trafficking and phosphatidylinositol 4-kinase III alpha in hepatitis C virus replication. Proc Natl Acad Sci U S A. 2009 May 05; 106(18):7577-82. View in: PubMed

  37. Tan Z, Randall G, Fan J, Camoretti-Mercado B, Brockman-Schneider R, Pan L, Solway J, Gern JE, Lemanske RF, Nicolae D, Ober C. Allele-specific targeting of microRNAs to HLA-G and risk of asthma. Am J Hum Genet. 2007 Oct; 81(4):829-34. View in: PubMed

  38. Randall G, Panis M, Cooper JD, Tellinghuisen TL, Sukhodolets KE, Pfeffer S, Landthaler M, Landgraf P, Kan S, Lindenbach BD, Chien M, Weir DB, Russo JJ, Ju J, Brownstein MJ, Sheridan R, Sander C, Zavolan M, Tuschl T, Rice CM. Cellular cofactors affecting hepatitis C virus infection and replication. Proc Natl Acad Sci U S A. 2007 Jul 31; 104(31):12884-9. View in: PubMed

  39. Randall G, Chen L, Panis M, Fischer AK, Lindenbach BD, Sun J, Heathcote J, Rice CM, Edwards AM, McGilvray ID. Silencing of USP18 potentiates the antiviral activity of interferon against hepatitis C virus infection. Gastroenterology. 2006 Nov; 131(5):1584-91. View in: PubMed

  40. Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grässer FA, van Dyk LF, Ho CK, Shuman S, Chien M, Russo JJ, Ju J, Randall G, Lindenbach BD, Rice CM, Simon V, Ho DD, Zavolan M, Tuschl T. Identification of microRNAs of the herpesvirus family. Nat Methods. 2005 Apr; 2(4):269-76. View in: PubMed

  41. Chen YL, Graham MD, de Pablo JJ, Randall GC, Gupta M, Doyle PS. Conformation and dynamics of single DNA molecules in parallel-plate slit microchannels. Phys Rev E Stat Nonlin Soft Matter Phys. 2004 Dec; 70(6 Pt 1):060901. View in: PubMed

  42. Randall G, Rice CM. Interfering with hepatitis C virus RNA replication. Virus Res. 2004 Jun 01; 102(1):19-25. View in: PubMed

  43. Zhang J, Randall G, Higginbottom A, Monk P, Rice CM, McKeating JA. CD81 is required for hepatitis C virus glycoprotein-mediated viral infection. J Virol. 2004 Feb; 78(3):1448-55. View in: PubMed

  44. Randall G, Grakoui A, Rice CM. Clearance of replicating hepatitis C virus replicon RNAs in cell culture by small interfering RNAs. Proc Natl Acad Sci U S A. 2003 Jan 07; 100(1):235-40. View in: PubMed

  45. Randall G, Lagunoff M, Roizman B. Herpes simplex virus 1 open reading frames O and P are not necessary for establishment of latent infection in mice. J Virol. 2000 Oct; 74(19):9019-27. View in: PubMed

  46. Randall G, Roizman B. Transcription of the derepressed open reading frame P of herpes simplex virus 1 precludes the expression of the antisense gamma(1)34.5 gene and may account for the attenuation of the mutant virus. J Virol. 1997 Oct; 71(10):7750-7. View in: PubMed

  47. Randall G, Lagunoff M, Roizman B. The product of ORF O located within the domain of herpes simplex virus 1 genome transcribed during latent infection binds to and inhibits in vitro binding of infected cell protein 4 to its cognate DNA site. Proc Natl Acad Sci U S A. 1997 Sep 16; 94(19):10379-84. View in: PubMed

  48. Lagunoff M, Randall G, Roizman B. Phenotypic properties of herpes simplex virus 1 containing a derepressed open reading frame P gene. J Virol. 1996 Mar; 70(3):1810-7. View in: PubMed