Sharon Lewin

Sharon Ruth Lewin AO, FRACP, FAHMS is an Australian Infectious Disease physician and researcher, and the inaugural director of The Peter Doherty Institute for Infection and Immunity, a joint venture between the University of Melbourne and the Royal Melbourne Hospital. She leads a multi-disciplinary research team working on mechanisms of HIV latency, clinical trials advancing potential HIV cure strategies and how HIV is affected by co-infections such as Hepatitis B. Lewin has extensive experience in scientific leadership, and is a strong advocate for community engagement and partnership in research.

Sharon Ruth Lewin
Sharon Lewin in November 2017, ASHM Conference in Canberra, Australia
Born
Melbourne, Australia
Alma materMonash University (MBBS) Monash University (PhD)
Known forHIV persistence and latency, HIV/HBV co-infection
AwardsFrank Fenner Award (2011)

Melburnian of the Year (2014) Peter Wills Medal (2015)

Officer of the Order of Australia (AO, 2019)
Scientific career
FieldsMedicine, Immunology, Virology
InstitutionsThe Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital

Monash University, Department of Infectious Diseases Alfred Hospital, Infectious Diseases

Burnet Institute

Research and accomplishments

Lewin began her research career just as highly active antiretroviral treatment emerged as a transformative influence on the lives of people living with HIV. Drawn to study HIV because of its enormous global challenge, along with the complex social issues, complex medicine and potentially transformative science, Lewin's research interests have developed from questions arising during the clinical care of people living with HIV. Detecting, quantifying and potentially reactivating latent HIV is a central theme of Lewin's research, which spans basic virology, cellular immunology and clinical research. Her research laboratory is run together with immunologist and clinician Associate Professor Paul Cameron, with whom she has developed a long-standing collaboration and partnership. Lewin has authored over 250 peer-reviewed publications.

While completing her postdoctoral training with David Ho at the Aaron Diamond AIDS Research Centre, Lewin developed a highly sensitive PCR method to detect unspliced HIV RNA, an early product of viral transcription, in people receiving antiretroviral drugs.[1] Over 20 years later, this method still informs studies of residual HIV replication, HIV latency and viral reactivation. Lewin's laboratory has developed models of HIV latency which are used to further tease out the mechanisms involved, and to assess the impact of latency reversal agents. Lewin's lab has shown that triggering the CCR7 receptor on resting CD4 T cells can induce latency,[2] acting through the activation of the cellular cytoskeleton, particularly actin remodelling.[3] This chemokine-induced latency model has been used in a comprehensive comparison of in vitro models for evaluating latency reversal agents.[4] Lewin's laboratory has also described the role of myeloid dendritic cells[5] and other antigen-presenting cells[6] in establishing HIV latency.

Lewin's team have made contributions to the knowledge of the HIV reservoir during antiretroviral treatment. This includes studies of naive CD4 T cells, where longitudinal and cross-sectional studies have shown that both CD31+ and CD31- naive CD4 T cells contribute to the ongoing HIV reservoir[7] and that HIV DNA is preferentially found in CD4 T cells expressing the chemokine receptors CXCR3 and CCR6.[8] Lewin's group has also studied immune reconstitution after antiretroviral treatment begins, exposing some of the factors associated with faster reconstitution[9] and has demonstrated7 a link between immune reconstitution and variants in the IL-7R gene.[10][11]

Lewin's research has elucidated some of the basic immunology of Hepatitis B infection alone[12] and in co-infection with HIV.[13] Ongoing research is providing a deeper understanding of the clinical consequences of co-infection with Hepatitis B and HIV, both in Australian participants[14][15] and through a long-standing collaboration with Thai researchers.[16][17][18][19]

Lewin's clinical research efforts have focussed on potential HIV cure strategies, particularly those using the epigenetic modifiers including histone deacetylase inhibitors (HDACis).[20][21] In vitro experiments showed that HDACis such as entinostat,[22] metacept-1 and -3[23] could activate latent HIV in primary T cells. Following a sabbatical working with Christine Katlama and Brigitte Autran at the Hopital Pitié-Salpêtrière and Université Pierre et Marie Curie (UPMC), Paris, Lewin began to focus more on moving potential cure strategies into clinical trials.[24] Lewin's lab conducted the first multi-dose proof-of-concept HDACi trial in HIV positive participants, administering vorinostat daily over a 14-day period and assessing safety and impact on HIV transcription and reservoirs.[25] The trial and follow-on study[26] showed that while vorinostat was safe and able to increase HIV transcription in most participants, it did not reduce the HIV reservoir.[25] A dose-escalation study conducted in Melbourne, Australia and San Francisco, California, USA of the anti-alcohol compound Disulfiram also showed the ability to increase levels of cell-associated unspliced HIV RNA.[27] Both vorinostat and Disulfiram are now being investigated as part of a combination approach to latency activation ('kick' or 'tickle') followed by a second intervention to remove cells harbouring reactivated virus ('kill' or 'tease').

Lewin has been invited to present at international conferences, and gave the opening plenary at the International AIDS Conference in Vienna in 2010 to an audience of over 10,000. Lewin is also an international scientific advocate, was local co-chair for the International AIDS Conference (AIDS 2014) in Melbourne, a member of WHO and UNAIDS strategic advisory groups and lead co-author of the 2016 International AIDS Society global scientific strategy to achieve an HIV cure.[28] Lewin is a founding council member of the Academy of Health and Medical Sciences, elected member of the Governing Council of the International AIDS Society representing the Asia Pacific region, member of the council of the National Health and Medical Research Council (NHMRC) of Australia and chairs the Health Translation Advisory Committee. She chairs the Ministerial Advisory Committee on Blood Borne Viruses and Sexually Transmitted Infections, the peak advisory group to the Minister of Health of Australia.

Awards and honours
  • David Rosenthal Memorial Prize for top student in 3rd year medicine and 2nd year anatomy (1984)
  • Robert Power Prize in Surgery[29] (1986)
  • Sophie Davis Memorial Prize[30] (1986)
  • The Ian Gust Prize, Macfarlane Burnet Centre for Medical Research (1993)
  • Frank Fenner Award, Burnet Institute[31] (2011)
  • Victorian AIDS Council/Gay Men's Health Centre Annual Research Award[32] (2011)
  • The 20th Annual B. Frank Polk HIV Research Lecture, Johns Hopkins University[33] (2014)
  • The Gertrude Ellon Distinguished Lecture in Virology, Miami (2014)
  • Foundation Fellow of the Australian Academy of Health and Medical Sciences[34] (2014)
  • Melburnian of the Year[35] (2014)
  • RD Wright Lecturer[36] (2015)
  • Peter Wills Medal[37] (2015)
  • The In Style Magazine and Audi Women of Style Award in Science[38] (2016)
  • Nadine Watson Lecturer[39] (2017)
  • Officer of the Order of Australia (2019) "For distinguished service to medical research, and to education, in the field of infectious diseases, particularly HIV/AIDS."[40]

References
  1. Lewin, S. R.; Vesanen, M.; Kostrikis, L.; Hurley, A.; Duran, M.; Zhang, L.; Ho, D. D.; Markowitz, M. (July 1999). "Use of Real-Time PCR and Molecular Beacons To Detect Virus Replication in Human Immunodeficiency Virus Type 1-Infected Individuals on Prolonged Effective Antiretroviral Therapy". Journal of Virology. 73 (7): 6099–6103. doi:10.1128/JVI.73.7.6099-6103.1999. ISSN 0022-538X. PMC 112674. PMID 10364365.
  2. Saleh, Suha; Solomon, Ajantha; Wightman, Fiona; Xhilaga, Miranda; Cameron, Paul U.; Lewin, Sharon R. (2007-12-15). "CCR7 ligands CCL19 and CCL21 increase permissiveness of resting memory CD4+ T cells to HIV-1 infection: a novel model of HIV-1 latency". Blood. 110 (13): 4161–4164. doi:10.1182/blood-2007-06-097907. ISSN 0006-4971. PMID 17881634.
  3. Cameron, Paul U.; Saleh, Suha; Sallmann, Georgina; Solomon, Ajantha; Wightman, Fiona; Evans, Vanessa A.; Boucher, Genevieve; Haddad, Elias K.; Sekaly, Rafick-Pierre (2010-09-28). "Establishment of HIV-1 latency in resting CD4+ T cells depends on chemokine-induced changes in the actin cytoskeleton". Proceedings of the National Academy of Sciences. 107 (39): 16934–16939. Bibcode:2010PNAS..10716934C. doi:10.1073/pnas.1002894107. ISSN 0027-8424. PMC 2947912. PMID 20837531.
  4. Spina, Celsa A.; Anderson, Jenny; Archin, Nancie M.; Bosque, Alberto; Chan, Jonathan; Famiglietti, Marylinda; Greene, Warner C.; Kashuba, Angela; Lewin, Sharon R. (2013-12-26). "An In-Depth Comparison of Latent HIV-1 Reactivation in Multiple Cell Model Systems and Resting CD4+ T Cells from Aviremic Patients". PLOS Pathogens. 9 (12): e1003834. doi:10.1371/journal.ppat.1003834. ISSN 1553-7374. PMC 3873446. PMID 24385908.
  5. Evans, Vanessa A.; Kumar, Nitasha; Filali, Ali; Procopio, Francesco A.; Yegorov, Oleg; Goulet, Jean-Philippe; Saleh, Suha; Haddad, Elias K.; Pereira, Candida da Fonseca (2013-12-05). "Myeloid Dendritic Cells Induce HIV-1 Latency in Non-proliferating CD4+ T Cells". PLOS Pathogens. 9 (12): e1003799. doi:10.1371/journal.ppat.1003799. ISSN 1553-7374. PMC 3855553. PMID 24339779.
  6. Kumar, Nitasha A.; Cheong, Karey; Powell, David R.; da Fonseca Pereira, Candida; Anderson, Jenny; Evans, Vanessa A.; Lewin, Sharon R.; Cameron, Paul U. (2015-09-11). "The role of antigen presenting cells in the induction of HIV-1 latency in resting CD4+ T-cells". Retrovirology. 12: 76. doi:10.1186/s12977-015-0204-2. ISSN 1742-4690. PMC 4567795. PMID 26362311.
  7. Wightman, Fiona; Solomon, Ajantha; Khoury, Gabriela; Green, Justin A.; Gray, Lachlan; Gorry, Paul R.; Ho, Yung Shwen; Saksena, Nitin K.; Hoy, Jennifer (2010-12-01). "Both CD31+ and CD31- Naive CD4+ T Cells Are Persistent HIV Type 1-Infected Reservoirs in Individuals Receiving Antiretroviral Therapy". The Journal of Infectious Diseases. 202 (11): 1738–1748. doi:10.1086/656721. ISSN 0022-1899. PMID 20979453.
  8. Khoury, Gabriela; Anderson, Jenny L.; Fromentin, Rémi; Hartogenesis, Wendy; Smith, Miranda Z.; Bacchetti, Peter; Hecht, Frederick M.; Chomont, Nicolas; Cameron, Paul U. (2016-06-19). "Persistence of integrated HIV DNA in CXCR3 + CCR6 + memory CD4+ T cells in HIV-infected individuals on antiretroviral therapy". AIDS. 30 (10): 1511–1520. doi:10.1097/qad.0000000000001029. ISSN 0269-9370. PMC 4889535. PMID 26807971.
  9. Rajasuriar, Reena; Gouillou, Maelenn; Spelman, Tim; Read, Tim; Hoy, Jennifer; Law, Matthew; Cameron, Paul U.; Petoumenos, Kathy; Lewin, Sharon R. (2011-06-02). "Clinical Predictors of Immune Reconstitution following Combination Antiretroviral Therapy in Patients from the Australian HIV Observational Database". PLOS ONE. 6 (6): e20713. Bibcode:2011PLoSO...620713R. doi:10.1371/journal.pone.0020713. ISSN 1932-6203. PMC 3107235. PMID 21674057.
  10. Rajasuriar, R.; Booth, D. R.; Gouillou, M.; Spelman, T.; James, I.; Solomon, A.; Chua, K.; Stewart, G.; Deeks, S. (January 2012). "The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART". Genes and Immunity. 13 (1): 83–93. doi:10.1038/gene.2011.65. ISSN 1466-4879. PMID 21938017.
  11. Rajasuriar, Reena; Booth, David; Solomon, Ajantha; Chua, Kyra; Spelman, Tim; Gouillou, Maelenn; Schlub, Timothy E.; Davenport, Miles; Crowe, Suzanne (2010-10-15). "Biological Determinants of Immune Reconstitution in HIV-Infected Patients Receiving Antiretroviral Therapy: The Role of Interleukin 7 and Interleukin 7 Receptor α and Microbial Translocation". The Journal of Infectious Diseases. 202 (8): 1254–1264. doi:10.1086/656369. ISSN 0022-1899. PMID 20812848.
  12. Chang, J. Judy; Thompson, Alexander J. V.; Visvanathan, Kumar; Kent, Stephen J.; Cameron, Paul U.; Wightman, Fiona; Desmond, Paul; Locarnini, Stephen A.; Lewin, Sharon R. (2007-11-01). "The phenotype of hepatitis B virus–specific T cells differ in the liver and blood in chronic hepatitis B virus infection". Hepatology. 46 (5): 1332–1340. doi:10.1002/hep.21844. ISSN 1527-3350. PMID 17924445.
  13. Chang, J. Judy; Wightman, Fiona; Bartholomeusz, Angeline; Ayres, Anna; Kent, Stephen J.; Sasadeusz, Joseph; Lewin, Sharon R. (2005-03-01). "Reduced Hepatitis B Virus (HBV)-Specific CD4+ T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy". Journal of Virology. 79 (5): 3038–3051. doi:10.1128/jvi.79.5.3038-3051.2005. ISSN 0022-538X. PMC 548440. PMID 15709024.
  14. Lewin, Sharon R.; Ribeiro, Ruy M.; Walters, Tomos; Lau, George K.; Bowden, Scott; Locarnini, Stephen; Perelson, Alan S. (2001-11-01). "Analysis of hepatitis B viral load decline under potent therapy: Complex decay profiles observed". Hepatology. 34 (5): 1012–1020. doi:10.1053/jhep.2001.28509. ISSN 1527-3350. PMID 11679973.
  15. Audsley, Jennifer; Robson, Christopher; Aitchison, Stacey; Matthews, Gail V.; Iser, David; Sasadeusz, Joe; Lewin, Sharon R. (2016-01-01). "Liver Fibrosis Regression Measured by Transient Elastography in Human Immunodeficiency Virus (HIV)-Hepatitis B Virus (HBV)-Coinfected Individuals on Long-Term HBV-Active Combination Antiretroviral Therapy". Open Forum Infectious Diseases. 3 (1): ofw035. doi:10.1093/ofid/ofw035. PMC 4800457. PMID 27006960.
  16. Matthews, Gail V.; Avihingsanon, Anchalee; Lewin, Sharon R.; Amin, Janaki; Rerknimitr, Rungsun; Petcharapirat, Panusit; Marks, Pip; Sasadeusz, Joe; Cooper, David A. (2008-10-01). "A randomized trial of combination hepatitis B therapy in HIV/HBV coinfected antiretroviral naïve individuals in Thailand". Hepatology. 48 (4): 1062–1069. doi:10.1002/hep.22462. ISSN 1527-3350. PMID 18697216.
  17. Crane, Megan; Sirivichayakul, Sunee; Chang, J. Judy; Avihingsanon, Anchalee; Ubolyam, Sasiwimol; Buranapraditkun, Supranee; Thantiworasit, Pattarawat; Wightman, Fiona; Locarnini, Stephen (2010-03-15). "No Increase in Hepatitis B Virus (HBV)-Specific CD8+ T Cells in Patients with HIV-1-HBV Coinfections following HBV-Active Highly Active Antiretroviral Therapy". Journal of Virology. 84 (6): 2657–2665. doi:10.1128/jvi.02124-09. ISSN 0022-538X. PMC 2826062. PMID 20053751.
  18. Crane, Megan; Avihingsanon, Anchalee; Rajasuriar, Reena; Velayudham, Pushparaj; Iser, David; Solomon, Ajantha; Sebolao, Baotuti; Tran, Andrew; Spelman, Tim (2014-09-01). "Lipopolysaccharide, Immune Activation, and Liver Abnormalities in HIV/Hepatitis B Virus (HBV)–Coinfected Individuals Receiving HBV-Active Combination Antiretroviral Therapy". The Journal of Infectious Diseases. 210 (5): 745–751. doi:10.1093/infdis/jiu119. ISSN 0022-1899. PMID 24585898.
  19. Punyawudho, Baralee; Thammajaruk, Narukjaporn; Thongpeang, Parawee; Matthews, Gail; Lewin, Sharon R.; Burger, David; Ruxrungtham, Kiat; Avihingsanon, Anchalee (2015). "Population pharmacokinetics of tenofovir in HIV/HBV co-infected patients". International Journal of Clinical Pharmacology and Therapeutics. 53 (11): 947–954. doi:10.5414/cp202386. PMID 26308175.
  20. Rasmussen, Thomas Aagaard; Søgaard, Ole Schmeltz; Brinkmann, Christel; Wightman, Fiona; Lewin, Sharon R.; Melchjorsen, Jesper; Dinarello, Charles; Østergaard, Lars; Tolstrup, Martin (2013-05-14). "Comparison of HDAC inhibitors in clinical development". Human Vaccines & Immunotherapeutics. 9 (5): 993–1001. doi:10.4161/hv.23800. ISSN 2164-5515. PMC 3899169. PMID 23370291.
  21. Wightman, Fiona; Ellenberg, Paula; Churchill, Melissa; Lewin, Sharon R. (January 2012). "HDAC inhibitors in HIV". Immunology and Cell Biology. 90 (1): 47–54. doi:10.1038/icb.2011.95. ISSN 0818-9641. PMID 22083528.
  22. Wightman, Fiona; Lu, Hao K.; Solomon, Ajantha E.; Saleh, Suha; Harman, Andrew N.; Cunningham, Anthony L.; Gray, Lachlan; Churchill, Melissa; Cameron, Paul U. (2013). "Entinostat is a histone deacetylase inhibitor selective for class 1 histone deacetylases and activates HIV production from latently infected primary T cells". AIDS. 27 (18): 2853–2862. doi:10.1097/qad.0000000000000067. PMC 4079759. PMID 24189584.
  23. Shehu-Xhilaga, Miranda; Rhodes, David; Wightman, Fiona; Liu, Hong B; Solomon, Ajantha; Saleh, Suha; Dear, Anthony E; Cameron, Paul U; Lewin, Sharon R (2009). "The novel histone deacetylase inhibitors metacept-1 and metacept-3 potently increase HIV-1 transcription in latently infected cells". AIDS. 23 (15): 2047–2050. doi:10.1097/qad.0b013e328330342c. PMID 19609198.
  24. Lewin, Sharon R; Rouzioux, Christine (2011). "HIV cure and eradication: how will we get from the laboratory to effective clinical trials?". AIDS. 25 (7): 885–897. doi:10.1097/qad.0b013e3283467041. PMID 21422987.
  25. Elliott, Julian H.; Wightman, Fiona; Solomon, Ajantha; Ghneim, Khader; Ahlers, Jeffrey; Cameron, Mark J.; Smith, Miranda Z.; Spelman, Tim; McMahon, James (2014-11-13). "Activation of HIV Transcription with Short-Course Vorinostat in HIV-Infected Patients on Suppressive Antiretroviral Therapy". PLOS Pathogens. 10 (11): e1004473. doi:10.1371/journal.ppat.1004473. ISSN 1553-7374. PMC 4231123. PMID 25393648.
  26. Mota, Talia M.; Rasmussen, Thomas A.; Rhodes, Ajantha; Tennakoon, Surekha; Dantanarayana, Ashanti; Wightman, Fiona; Hagenauer, Michelle; Roney, Janine; Spelman, Tim (2017-05-15). "No adverse safety or virological changes 2 years following vorinostat in HIV-infected individuals on antiretroviral therapy". AIDS. 31 (8): 1137–1141. doi:10.1097/qad.0000000000001442. ISSN 0269-9370. PMC 5496768. PMID 28301423.
  27. Elliott, Julian H; McMahon, James H; Chang, Christina C; Lee, Sulggi A; Hartogensis, Wendy; Bumpus, Namandje; Savic, Rada; Roney, Janine; Hoh, Rebecca (2015). "Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study". The Lancet HIV. 2 (12): e520–e529. doi:10.1016/s2352-3018(15)00226-x. PMC 5108570. PMID 26614966.
  28. Deeks, Steven G; Lewin, Sharon R; Ross, Anna Laura; Ananworanich, Jintanat; Benkirane, Monsef; Cannon, Paula; Chomont, Nicolas; Douek, Daniel; Lifson, Jeffrey D (2016). "International AIDS Society global scientific strategy: towards an HIV cure 2016" (PDF). Nature Medicine. 22 (8): 839–850. doi:10.1038/nm.4108. hdl:10044/1/45370. PMC 5322797. PMID 27400264.
  29. srivithp. "Prizes for medical students at Central Clinical School". www.med.monash.edu. Retrieved 2017-08-25.
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  31. Institute, Burnet. "2011 Fenner Award presented | Burnet Institute". www.burnet.edu.au. Retrieved 2017-08-25.
  32. Victorian AIDS Council Gay Men's Health Centre (25 August 2017). "Annual Report 2010-2011" (PDF).
  33. "Johns Hopkins Center for AIDS Research Newsletter May 2014" (PDF).
  34. "Fellowship of the Australian Academy of Health and Medical Sciences" (PDF). Australian Academy of Health and Medical Sciences. October 2016. Retrieved 11 September 2019.
  35. "2014 Melburnian of the Year - City of Melbourne". www.melbourne.vic.gov.au. Retrieved 2017-08-25.
  36. "R Douglas Wright Lecture 2015". Retrieved 2017-08-25.
  37. "Previous Award Winners - RESEARCH AUSTRALIA". RESEARCH AUSTRALIA. Retrieved 2017-08-25.
  38. "Instyle And Audi Celebrate Eighth Annual Awards - B&T". B&T. 2016-05-13. Retrieved 2017-08-25.
  39. "Leaders in Science and Society Seminars — Garvan Institute of Medical Research". www.garvan.org.au. Retrieved 2017-08-25.
  40. "Australia Day 2019 Honours List" (PDF). Governor General of the Commonwealth of Australia. 2019-01-26. Retrieved 2019-01-27.
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