January 24, 2013 -- 1. A*STAR’s Singapore Immunology Network (SIgN) and the Immunology Frontier Research Center (IFReC) of Osaka University jointly organised the second Network of Immunology Frontiers (NIF) Winter School on Advanced Immunology in Singapore from 20th to 25th January 2013. This international school on advanced immunology is part of a greater vision to make Asia a global hub of outstanding immunology research.
2. Twenty leading immunologist from around the world delivered lectures at the school which was attended by 54 postdoctoral and PhD students from 17 different countries including USA, UK, China, Australia, Japan and Singapore. A*STAR Chairman, Mr Lim Chuan Poh, was the guest-of-honour.
3. The highlight of this event would be the visit to A*STAR’s SIgN cutting-edge technology facilities on the last day of the program, which include the 2-Photon Intravital Bioimaging, Flow Cytometry, CyTOF technology. A hands-on demonstration session of these technologies would be conducted for the students.
4. For more information about the NIF (SIgN-IFReC) Winter School on Advanced Immunology, please visit http://ifrec-sign-winterschool.org/index.html
AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH (A*STAR)
Annex A – Speakers’ highlights: Biographies and Talk abstracts
Annex B – Program on Friday at A*STAR’s SIgN
Annex C – Map of SIgN
Annex D – Group photo of NIF 2013 participants
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Dr. Sarah Chang
Corporate Communications, Agency for Science, Technology and Research
Tel: (65) 6826 6442
About the Singapore Immunology Network (SIgN)
The Singapore Immunology Network (SIgN), officially inaugurated on 15 January 2008, is a research consortium under the Agency for Science, Technology and Research (A*STAR)’s Biomedical Research Council. The mandate of SIgN is to advance human immunology research and participate in international efforts to combat major health problems. Since its launch, SIgN has grown rapidly and currently includes 200 scientists from 25 different countries around the world working under 26 renowned principal investigators. At SIgN, researchers investigate immunity during infection and various inflammatory conditions including cancer and are supported by cutting edge technological research platforms and core services.
Through this, SIgN aims to build a strong platform in basic human immunology research for better translation of research findings into clinical applications. SIgN also sets out to establish productive links with local and international institutions, and encourage the exchange of ideas and expertise between academic, industrial and clinical partners and thus contribute to a vibrant research environment in Singapore.
For more information about SIgN, please visit www.sign.a-star.edu.sg
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences and physical sciences and engineering research institutes, and six consortia & centres, located in Biopolis and Fusionopolis as well as their immediate vicinity.
A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, and with other local and international partners.
For more information about A*STAR, please visit www.a-star.edu.sg
Prof. Olivera J. FINN
Designation Distinguished Professor, Chair
Affiliation Department of Immunology, University of Pittsburgh, School of Medicine, Pittsburgh, US; Chair of the IUIS Gender equality and Career development committee (International Union of Immunological Societies)
Olivera J. Finn, Ph.D. is Distinguished Professor and Chair of the Department of Immunology at the University of Pittsburgh School of Medicine and Co-Leader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute. She has an extensive track record of accomplishments in tumor immunology and cancer vaccines research reported in over 140 papers and numerous reviews and book chapters. She was the discoverer of the MUC1 antigen and has published over 150 papers in prestigious journals on the preclinical work leading to the development and evaluation of MUC1 cancer vaccines. She has been a co-investigator on seven clinical trials of various MUC1 vaccines in pancreatic, colon, breast, prostate and lung cancer. Dr. Finn also discovered cyclin B1 tumor antigen and published several papers on its potential as a cancer vaccine. She is on editorial boards of many cancer journals and advisory boards of many cancer centers and several companies. She is a member of the American Cancer Society Council. Dr. Finn has been active in several professional organizations. She is a member of the American Association of Immunologists (AAI) and served as AAI President in 2007-2008. She is a member of the American Association for Cancer Research (AACR) and served as Chair of the AACR Cancer Immunology Working Group 2010-2011. She also served as Councilor of the International Union of Immunology Societies (IUIS) and now chairs the IUIS Gender Equality and Career Development Committee. She has trained 40 PhD and MD/PhD students and numerous postdoctoral fellows.
Talk Abstract - Tumor Immunosurveillance
Numerous human tumor associated antigens have been characterized and a large number of them are effective in preventing tumor growth in appropriate animal models(1). Many have been tested as components of vaccines in Phase I and II trials in cancer patients. Because the cancer vaccine field focuses primarily on therapy of advanced cancer, limited attention has been given to antigens or forms of antigens that are less likely to be expressed on normal tissues. Our work defines the difference between self/tumor antigens to which tolerance is maintained and abnormal self/ tumor antigens perceived by the immune system as foreign and thus not subject to tolerance or autoimmunity(2, 3). These abnormal-self molecules are candidate antigens for safe and effective cancer vaccines. Our recent findings implicate these antigens in the immunosurveillance of cancer as well as diseases other than cancer, such as viral infections and chronic inflammatory diseases(4, 5). Unpublished results will be presented to show that viral infections can generate adaptive immune memory for abnormal self antigens that serve as tumor associated antigens. An example of an abnormal self/tumor antigen is the mucin MUC1(6). Data will be presented showing induction of immunity to the tumor MUC1 following non-malignant events and how that information has been used to run a clinical trial of a MUC1 vaccine for cancer prevention.
1. Finn OJ. Cancer immunology. N Engl J Med 2008; 358:2704-15.
2. Ryan SO, Vlad AM, Islam K, Gariepy J, Finn OJ. Tumor-associated MUC1 glycopeptide epitopes are not subject to self- tolerance and improve responses to MUC1 peptide epitopes in MUC1 transgenic mice. Biol Chem 2009; 390:611-8.
3. Ryan SO, Turner MS, Gariepy J, Finn OJ. Tumor antigen epitopes interpreted by the immune system as self or abnormal-self differentially affect cancer vaccine responses. Cancer Res 2010; 70:5788-96.
4. Cramer DW, Titus-Ernstoff L, McKolanis JR, Welch WR, Vitonis AF, Berkowitz RS, et al. Conditions associated with antibodies against the tumor-associated antigen MUC1 and their relationship to risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev 2005; 14:1125-31.
5. Cramer DW, Finn OJ. Epidemiologic perspective on immune-surveillance in cancer. Curr Opin Immunol; 23:265-71.
6. Vlad AM, Kettel JC, Alajez NM, Carlos CA, Finn OJ. MUC1 immunobiology: from discovery to clinical applications. Adv Immunol 2004; 82:249-93.
Prof. Xuetao CAO
Designation President and Professor of Immunology
Affiliation Chinese Academy of Medical Sciences, Beijing, China; President of FIMSA (Federation of Immunological Societies of Asia-Oceania)
Dr. Xuetao Cao, born in 1964, received his Ph.D. from Second Military Medical University (Shanghai, China) in 1990. He became Professor in Immunology in 1992 at the Second Military Medical University and the Director of the Institute of Immunology at the same University in 2001. He is now Professor and Director of National Key Laboratory of Medical Immunology (2006.5-), and President of Chinese Academy of Medical Sciences, Beijing, China (2011.8-). He is the President of Chinese Society for Immunology (2006.11-), Chief Scientist of 973 National Program of Immunology in China. He is currently President of FIMSA and member of 54th IUIS committee. He was elected as member of Chinese Academy of Engineering in 2005. He is the editorial board member of Annu Rev Immunol, Science Translational Medicine, J Immunol, JBC, Eur J Immunol, and Editor-in-Chief of Cell Mol Immunol, Associate Editor of Gene Therapy. His major interests are immunobiology of APCs (dendritic cells, macrophages), innate signaling and immune regulation, cancer immunotherapy. His group identified a new regulatory dendritic cell (DC) subset and found that splenic stroma could drive mature DC to differentiate into regulatory DC. His group proposed several new approaches for DC-based immunotherapy and gene therapy of cancer, and completed the Phase II clinical trial of DC vaccine approved by China FDA for the treatment of advanced colon cancer patients. His group has independently identified and functionally characterized more than 20 molecules from human DC. In recent years he is investigating the mechanisms for immune recognition and innate receptor TLR/RIG-I signaling. As corresponding author, he published 202 original papers in peer-reviewed journals including Nat Immunol, Immunity, Cancer Cell, J Exp Med, Blood, J Biol Chem, J Immunol, Cancer Res, etc.
Talk Abstract - Regulation of PRR-Triggered Innate Response and Inflammation
Innate immunity is the first line of host defense against infection. Pattern recognition receptors (PRRs) including Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs) are main sensors of the invading pathogens by recognizing pathogen-associated molecular patterns (PAMPs), the conserved and specific molecular signatures on pathogens, and RNA viruses. TLR ligation triggers distinct but shared signaling pathways that lead to effector mechanisms in innate immune responses. The TLR specificity and activation are strictly and finely tuned at multiple levels of the signal transduction pathways, resulting in complex signaling platforms. Many molecules, ranging from membrane and cytosol to nucleus, contribute to TLR ligand discrimination or receptor signaling, and play different roles in the regulation of TLR response via different mechanisms such as cross-regulation, protein modification, helper cofactors, posttranscriptional and epigenetic regulation. Better understanding of the mechanisms underlying the control of TLR signaling may provide new targets for therapeutic intervention to infections and inflammatory diseases. In addition, RIG-I is a critical RNA virus sensor that serves to initiate antiviral innate immunity. Insufficient IFN production causes chronic infection, while excessive IFN causes autoimmune and/or inflammatory diseases. Thus, precise control of RIG-I signaling is critical for efficient viral clearance without harmful immunopathology. Herein, I will summarize the most recent literatures that provide new insights into the cross-regulation of TLR/RIG-I signaling-triggered innate immune response.
Prof. Tomohiro KUROSAKI
Designation Principal Investigator
Affiliation Immunology Frontier Research Center (WPI-IFReC), Osaka University, Japan; Laboratory for Lymphocyte Differentiation, RIKEN; Research Centre for Allergy and Immunology, Japan
1980 Okayama University, Medical School (M.D.)
1987 Kyoto University, Graduate School of Medicine (Ph.D.)
1989-1992 Research Associate, Laboratory of Biochemical Genetics, Sloan-Kettering Institute, New York, NY
1992-1996 Senior Research Scientist, Department of Cardiovascular Molecular
Biology, Lederle Laboratories, Pearl River, NY
1996-2004 Professor, Kansai Medical University, Institute for Liver Research,
Department of Molecular Genetics
2004-present Group Director, Laboratory for Lymphocyte Differentiation, RIKEN
Research Center for Allergy and Immunology
2008-present Professor, Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University
Current Research Interest: B lymphocyte biology
Talk Abstract - Humoral Memory Responses
Memory B cells are a key cellular component for generating robust secondary IgG responses. By analyzing location of memory B and T cells and their functions, we propose three potential mechanisms of why such robust responses can be generated. First, IgG1 memory B cells can be found in association with contracted germinal centers (GCs). The retention of IgG1 memory B cells in such location may expedite reencounter with antigens. Second, reorganization of transcription factors inside B cells, caused by antigen experience, contributes to predisposition of IgG1 memory B cells toward plasma cell differentiation. Finally, Tfh memory T cells reside close to IgG1 memory B cells, again expediting cognate T-B interactions very rapidly. In addition, these Tfh memory T cells quickly upregulate Bcl6 by antigen presentation through memory B cells.
Prof. Shizuo AKIRA
Designation Professor, Director
Affiliation Immunology Frontier Research Center (WPI-IFReC), Osaka University, Japan
Shizuo Akira is a director and professor of WPI Immunology Frontier Research Center, and also a professor in Institute for Microbial Diseases at Osaka University, Japan. He received his M.D. and Ph.D. from Osaka University. After two years of postdoctoral working in Department of Immunology, University of California at Berkeley, he started to study on IL-6 gene regulation and signaling in the Institute for Molecular and Cellular Biology, Osaka University, and cloned transcription factors, NF-IL6(C/EBP beta) and STAT3. He was a professor in Department of Biochemistry, Hyogo College of Medicine from 1996 to 1999, where he became involved in Toll-like receptors research. By generating TLR family knockout mice, he identified ligands of many TLR members. He also demonstrated that the difference in signaling pathway among TLRs is due to selective usage of adaptor molecules such as MyD88 and TRIF. He demonstrated that pathogen-derived RNA is recognized by cytoplasmic receptor family, besides TLRs, and clarified the molecular mechanism of antiviral response against RNA viruses. His current research interests are molecular mechanisms of innate immunity and inflammation, which are studied mainly by generating knockout mice.
Talk Abstract - mRNA Stability in the Immune Response
Immune responses are accompanied by dynamic changes in gene expression. Gene expression is controlled at multiple points, including signal transduction, transcription and mRNA stability. So far, transcriptional regulation has been extensively studied. Many transcription factors including NF-?B and AP-1 are involved in induction of genes involved in inflammatory and immune responses. However, recent studies have revealed that control of gene expression at the mRNA level is as important as transcriptional control in the immune response. Gene expression profiles obtained from human Jurkat T cells stimulated with PMA plus ionomycin revealed that regulation of mRNA stability may account for as much as 50% of all measurements of changes in total cellular polyA mRNA. We have recently identified a novel gene named Zc3h12a which has a CCCH-type zinc finger domain. The knockout mice developed spontaneous autoimmune diseases accompanied by splenomegaly and lymphadenopathy. Subsequent studies showed that Zc3h12a is a nuclease involved in destabilization of IL-6 and IL-12mRNA via the stem loop structure present in the 3’UTR of these genes. We renamed it Regulatory RNase-1 (Regnase-1) based on the function. As an example showing the importance of mRNA stability, I would like to discuss the role of Regnase-1 in the immune response.
Program Outline on Friday, 25 Jan 2013 at A*STAR’s SIgN
10:30 am - 11:15 am
Regulation of PRR-Triggered Innate Response and Inflammation
Chinese Academy of Medical Sciences
11:15 am - 12:00 pm
Olivera J. FINN
University of Pittsburgh School of Medicine
12:00 pm - 12:45 pm
Introduction to SIgN & Institute Tour
12:45 pm - 1:30 pm
1:30 pm - 4:00 pm
Cutting-Edge Technology Demonstrations
BD Technology in a Milestone by BD Singapore
Flow Cytometry in Detecting Infectious Diseases by BD USA
Flow Cytometry in SIgN Research
Case Study: Designing Experiments by BD Singapore
4:00 pm - 4:15 pm
4:15 pm - 5:00 pm
Cutting-Edge Technology Demonstrations
CyTOF Data Analysis by Dr. Evan NEWELL & Dr. Anis LARBI (SIgN, A*STAR)
Bioimaging Analysis by Dr. Lai Guan NG (SIgN, A*STAR)
5:00 pm - 5:30pm
Closing Remark by Paola CASTAGNOLI
Scientific Director, SIgN & Chair of NIF 2013
For more details on program outline on 20th to 24th Jan 2013, please visit http://ifrec-sign-winterschool.org/program.html