Wikipedia

Sharon Lewin

Sharon Ruth Lewin AO, FAA, FRACP, FAHMS is an Australian physician who is the inaugural Director of The Peter Doherty Institute for Infection and Immunity (Doherty Institute). She is also a Professor of Medicine at The University of Melbourne, a National Health and Medical Research Council (NHMRC) Practitioner Fellow, Director of the Cumming Global Centre for Pandemic Therapeutics, and President of the International AIDS Society (IAS).

Sharon Ruth Lewin
Lewin in November 2017
Born
Melbourne, Australia
Alma materMonash University
Known forHIV persistence and latency, HIV/HBV co-infection, COVID-19
SpouseRobert Milstein[1]
Awards
  • Peter Wills Medal (2015)
  • Officer of the Order of Australia (2019)
  • Robert C. Gallo Award for Scientific Excellence and Leadership in Medical Virology (2020)
  • Medal for Outstanding Female Researcher (2022)
Scientific career
FieldsMedicine, immunology, V\virology
InstitutionsThe Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital
Monash University, Department of Infectious Diseases
Alfred Hospital
Burnet Institute
Scholia has a profile for Sharon R. Lewin (Q37618308).

Research and accomplishments edit

Lewin began her research career just as an antiretroviral treatment emerged for people living with HIV.[citation needed] Drawn to study HIV because of its global challenge, along with the complex social issues, 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 Paul Cameron.[citation needed]

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.[2] 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.[citation needed] Lewin's lab has shown that triggering the CCR7 receptor on resting CD4 T cells can induce latency,[3] acting through the activation of the cellular cytoskeleton, particularly actin remodelling.[4] This chemokine-induced latency model has been used in a comprehensive comparison of in vitro models for evaluating latency reversal agents.[5] Lewin's laboratory has also described the role of myeloid dendritic cells[6] and other antigen-presenting cells[7] 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[8] and that HIV DNA is preferentially found in CD4 T cells expressing the chemokine receptors CXCR3 and CCR6.[9] Lewin's group has also studied immune reconstitution after antiretroviral treatment begins, exposing some of the factors associated with faster reconstitution[10] and has demonstrated a link between immune reconstitution and variants in the IL-7R gene.[11][12]

Lewin's research has elucidated some of the basic immunology of Hepatitis B infection alone[13] and in co-infection with HIV.[14] Ongoing research is providing a deeper understanding of the clinical consequences of co-infection with Hepatitis B and HIV, both in Australian participants[15][16] and through a long-standing collaboration with Thai researchers.[17][18][19][20]

Lewin's clinical research efforts have focussed on potential HIV cure strategies, particularly those using the epigenetic modifiers including histone deacetylase inhibitors (HDACis).[21][22] In vitro experiments showed that HDACis such as entinostat,[23] metacept-1 and -3[24] 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.[25] 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.[26] The trial and follow-on study[27] showed that while vorinostat was safe and able to increase HIV transcription in most participants, it did not reduce the HIV reservoir.[26] 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.[28] 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 gave the opening plenary at the International AIDS Conference in Vienna in 2010.[citation needed] Lewin 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.[29] 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, she became President of the International AIDS Society in 2022 for a two-year tenure,[30] 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.[citation needed]

Awards and honours edit

References edit

  1. ^ Monash University Distinguished Alumni Sharon Lewin
  2. ^ 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.
  3. ^ Saleh, Suha; Solomon, Ajantha; Wightman, Fiona; Xhilaga, Miranda; Cameron, Paul U.; Lewin, Sharon R. (15 December 2007). "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.
  4. ^ Cameron, Paul U.; Saleh, Suha; Sallmann, Georgina; Solomon, Ajantha; Wightman, Fiona; Evans, Vanessa A.; Boucher, Genevieve; Haddad, Elias K.; Sekaly, Rafick-Pierre (28 September 2010). "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.
  5. ^ Spina, Celsa A.; Anderson, Jenny; Archin, Nancie M.; Bosque, Alberto; Chan, Jonathan; Famiglietti, Marylinda; Greene, Warner C.; Kashuba, Angela; Lewin, Sharon R. (26 December 2013). "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.
  6. ^ Evans, Vanessa A.; Kumar, Nitasha; Filali, Ali; Procopio, Francesco A.; Yegorov, Oleg; Goulet, Jean-Philippe; Saleh, Suha; Haddad, Elias K.; Pereira, Candida da Fonseca (5 December 2013). "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.
  7. ^ Kumar, Nitasha A.; Cheong, Karey; Powell, David R.; da Fonseca Pereira, Candida; Anderson, Jenny; Evans, Vanessa A.; Lewin, Sharon R.; Cameron, Paul U. (11 September 2015). "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.
  8. ^ Wightman, Fiona; Solomon, Ajantha; Khoury, Gabriela; Green, Justin A.; Gray, Lachlan; Gorry, Paul R.; Ho, Yung Shwen; Saksena, Nitin K.; Hoy, Jennifer (1 December 2010). "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.
  9. ^ Khoury, Gabriela; Anderson, Jenny L.; Fromentin, Rémi; Hartogenesis, Wendy; Smith, Miranda Z.; Bacchetti, Peter; Hecht, Frederick M.; Chomont, Nicolas; Cameron, Paul U. (19 June 2016). "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.
  10. ^ Rajasuriar, Reena; Gouillou, Maelenn; Spelman, Tim; Read, Tim; Hoy, Jennifer; Law, Matthew; Cameron, Paul U.; Petoumenos, Kathy; Lewin, Sharon R. (2 June 2011). "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.
  11. ^ 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.
  12. ^ Rajasuriar, Reena; Booth, David; Solomon, Ajantha; Chua, Kyra; Spelman, Tim; Gouillou, Maelenn; Schlub, Timothy E.; Davenport, Miles; Crowe, Suzanne (15 October 2010). "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.
  13. ^ 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. (1 November 2007). "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. S2CID 9902334.
  14. ^ Chang, J. Judy; Wightman, Fiona; Bartholomeusz, Angeline; Ayres, Anna; Kent, Stephen J.; Sasadeusz, Joseph; Lewin, Sharon R. (1 March 2005). "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.
  15. ^ Lewin, Sharon R.; Ribeiro, Ruy M.; Walters, Tomos; Lau, George K.; Bowden, Scott; Locarnini, Stephen; Perelson, Alan S. (1 November 2001). "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. S2CID 206249432.
  16. ^ Audsley, Jennifer; Robson, Christopher; Aitchison, Stacey; Matthews, Gail V.; Iser, David; Sasadeusz, Joe; Lewin, Sharon R. (1 January 2016). "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.
  17. ^ Matthews, Gail V.; Avihingsanon, Anchalee; Lewin, Sharon R.; Amin, Janaki; Rerknimitr, Rungsun; Petcharapirat, Panusit; Marks, Pip; Sasadeusz, Joe; Cooper, David A. (1 October 2008). "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.
  18. ^ Crane, Megan; Sirivichayakul, Sunee; Chang, J. Judy; Avihingsanon, Anchalee; Ubolyam, Sasiwimol; Buranapraditkun, Supranee; Thantiworasit, Pattarawat; Wightman, Fiona; Locarnini, Stephen (15 March 2010). "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.
  19. ^ Crane, Megan; Avihingsanon, Anchalee; Rajasuriar, Reena; Velayudham, Pushparaj; Iser, David; Solomon, Ajantha; Sebolao, Baotuti; Tran, Andrew; Spelman, Tim (1 September 2014). "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.
  20. ^ 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.
  21. ^ Rasmussen, Thomas Aagaard; Søgaard, Ole Schmeltz; Brinkmann, Christel; Wightman, Fiona; Lewin, Sharon R.; Melchjorsen, Jesper; Dinarello, Charles; Østergaard, Lars; Tolstrup, Martin (14 May 2013). "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.
  22. ^ 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. S2CID 21811612.
  23. ^ 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.
  24. ^ 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. S2CID 39280869.
  25. ^ 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. S2CID 23266836.
  26. ^ a b Elliott, Julian H.; Wightman, Fiona; Solomon, Ajantha; Ghneim, Khader; Ahlers, Jeffrey; Cameron, Mark J.; Smith, Miranda Z.; Spelman, Tim; McMahon, James (13 November 2014). "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.
  27. ^ Mota, Talia M.; Rasmussen, Thomas A.; Rhodes, Ajantha; Tennakoon, Surekha; Dantanarayana, Ashanti; Wightman, Fiona; Hagenauer, Michelle; Roney, Janine; Spelman, Tim (15 May 2017). "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.
  28. ^ 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.
  29. ^ 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.
  30. ^ "Sharon Lewin assumes IAS Presidency". www.iasociety.org. Retrieved 11 May 2023.
  31. ^ Natoli, Andrea (6 April 2016). "2015 Peter Wills Medal: Prof Sharon Lewin". RESEARCH AUSTRALIA. Retrieved 15 March 2024.
  32. ^ "Australia Day 2019 Honours List" (PDF). Governor General of the Commonwealth of Australia. 26 January 2019. Retrieved 27 January 2019.
  33. ^ "Professor Sharon Lewin presented with GVN Robert C Gallo Award". www.doherty.edu.au. The Doherty Institute. 22 September 2020. Retrieved 15 March 2024.
  34. ^ "Sharon Lewin AO, FRACP PhD FAHMS and RMIT University win 2020 Melbourne Achiever Award". Committee For Melbourne. Retrieved 15 March 2024.
  35. ^ "PROFESSOR SHARON LEWIN AO". rotaryclubofmelbourne.org.au. Retrieved 15 March 2024.
  36. ^ Rowney, Katie (6 September 2022). "Professor Sharon Lewin awarded Medal for Outstanding Female Researcher - AAHMS". aahms.org. Retrieved 15 March 2024.
  37. ^ "Sharon Lewin". www.science.org.au. Retrieved 25 May 2023.
  38. ^ "La Trobe awards Hon Docs to global health pioneers". La Trobe University. 25 October 2023. Retrieved 1 November 2023.
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