Principal Investigator – Joint Appointee
Dr Antonio Bertoletti is an Infectious Diseases Doctor who has always been fascinated by the pathogenesis of viral infections. He began working in the field of viral hepatitis as a medical student at the University of Parma (Italy) and during his MD specialization (1989-93). He worked two years (1989-91) at The Scripps Research Institute (La Jolla) characterizing for the first time the Hepatitis B virus (HBV) specific cytotoxic T cell response in man. He worked in Italy (University of Parma 1991-95), in the MRC Unit in the Gambia (1995-97) and then in London at Institute of Hepatology-University College of London (1997-2005). He moved to Singapore in 2005 where he was the Director of Infection and Immunity Program at the Singapore Institute for Clinical Sciences (A*STAR) until 2013 before moving in 2013 at the Emerging Viral Disease Program at Duke-NUS Medical School. He keeps an Adjunct Position as Research Director, Viral Hepatitis at the Singapore Institutes for Clinical Sciences and he is also Honorary Professor of School of Immunity and Infection, College of Medical and Dental Science, University of Birmingham, Edgbaston, UK.
He was awarded in 2013 of the Singapore Translational Research Grant Award (STAR Award 2013-18) and he is the current Vice-President of the Singapore Society of Immunology. The research in his laboratories (Duke-NUS Emerging Viral Diseases Program and SICS- A-STAR) is focus on the development of new immunological based therapies (TCR-redirected T cells, HLA-peptide specific antibodies) for the treatment of HBV and Hepatocellularcarcinoma and on the characterization of human intrasinusoidal hepatic immune system.
Hepatitis B virus (HBV) infection is a predominant Asian health problem: of the 350 million people with chronic HBV infection (CHB) worldwide, approximately 75% live in Asia. Understanding the immune pathogenesis and developing immune-based therapies to cure this chronic viral infection and its major complication, hepatocellular carcinoma (HCC), is the main focus of their research. The laboratory relies on state-of-the-art methods (high-dimensional flow cytometry, gene expression profiling, laser micro-dissection of affected tissues) to find ways to understand HBV pathogenesis and overcome the immunological defects that cause viral persistence in CHB patients and HCC oncogenesis. They developed techniques and unique tools that allow them to genetically engineer functional T lymphocytes bearing T-cell receptors (TCRs) capable of recognizing and destroying HBV-and HCC cells. They are also interested to study the functionality of immune cells in the liver microenvironment. Finally, they demonstrated that patients with HBV-related HCC have HCC metastasis carrying the HBV peptide/MHC complex recognized by their genetically engineered T cells leading to a first-in-man clinical trial testing the clinical efficacy of TCR-redirected T cells in HBV-related HCC. Their goal is to further develop these therapeutic strategies and, ultimately, bring the most promising approaches to the clinic, thereby offering new and effective treatment options to patients with CHB and HCC.
Yeap WH, Wong KL, Shimasaki N, Teo EC, Quek JK, Yong HX, Diong CP, Bertoletti A, Linn YC, Wong SC. ''CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes''. Sci Rep. 27 Sep 2016. 6:34310. doi: 10.1038/srep34310.
Koh S, Shimasaki N, Bertoletti A. ''Redirecting T Cell Specificity Using T Cell Receptor Messenger RNA Electroporation''. Methods Mol Biol. 29 May 2016. 1428:285-96. doi: 10.1007/978-1-4939-3625-0_19.
Bertoletti A, Ferrari C. ''Adaptive immunity in HBV infection''. J Hepatol. 01 Apr 2016. 64(1 Suppl):S71-83. doi: 10.1016/j.jhep.2016.01.026.
Bertoletti A. ''T cell fitness in the liver: How can T cells keep it up?''. J Hepatol. 01 Mar 2016. 64(6):1208-10. doi: 10.1016/j.jhep.2016.02.035.
Yang N, Bertoletti A. ''Advances in therapeutics for chronic hepatitis B''. Hepatol Int. 12 Sep 2015. 10(2):277-85. doi: 10.1007/s12072-015-9661-x.
Hudspeth K, Donadon M, Cimino M, Pontarini E, Tentorio P, Preti M, Hong M, Bertoletti A, Bicciato S, Invernizzi P, Lugli E, Torzilli G, Gershwin ME, Mavilio D. ''Human liver-resident CD56bright/CD16neg NK cells are retained within hepatic sinusoids via the engagement of CCR5 and CXCR6 pathways''. J Autoimmun. 30 Aug 2015. 66:40-50. doi: 10.1016/j.jaut.2015.08.011.
Tan A, Koh S, Bertoletti A. ''Immune Response in Hepatitis B Virus Infection''. Cold Spring Harb Perspect Med. 01 Jul 2015. 5(8):a021428. doi: 10.1101/cshperspect.a021428.
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