SECTIONS
Epigenetics (-omics) in Development
Haruhiko Koseki, MD, PhD
"The role of PRC1 for ES cell maintenance"
Haruhiko Koseki, MD, PhD, Group Director of RIKEN Center for Allergy and Immunology (RCAI). Dr. Koseki’s work is focused on the functions of mammalian Polycomb group proteins in development and homeostasis and molecular mechanisms underlying Polycomb repression in mammals. Dr. Koseki has recently put particular emphasis to understand the role of Polycomb group proteins in various stem cells that include ES cells. Dr. Koseki received his Ph.D. degree from Chiba University School of Medicine. Following his postdoctoral research at Max-Planck Institute of Immunobiology in Freiburg, he joined the faculty of Chiba University Medical School in 1994, where he rose to the rank of Full Professor. Dr. Koseki moved to Yokohama Institute of RIKEN in 2004 to establish the RCAI.
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Hiroyuki Sasaki, MD, PhD
"Epigenetic regulation of imprinted genes and retrotransposons in the mammalian germline"
Hiroyuki Sasaki , MD, PhD, Professor and Chairperson of Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, Japan. Dr. Sasaki graduated from School of Medicine, Kyushu University, and began his research career investigating the molecular pathology of several human genetic disorders. After he received his Ph.D. from Kyushu University Graduate School in 1987, he switched his research to epigenetics. Following his postdoctoral research at the Babraham Institute and Wellcome/CRC Institute, he was appointed as an Associate Professor at the Institute of Genetic Information, Kyushu University, in 1993. Dr. Sasaki then moved to the National Institute of Genetics and obtained the current positions in 1998. Dr. Sasaki investigates the epigenetic mechanisms involved in genomic imprinting and germ cell development and also studies the epigenetic basis of some human diseases. His current research also focuses on the link between epigenetic mechanisms and small RNA regulatory pathways. Dr. Sasaki received the Japan Society of Human Genetics Junior Faculty Research Award (1997). He has served on the Councilors of the Japan Society of Human Genetics (2006-), the Organizers of the Mouse Molecular Genetics Meeting (2005-), and the Associate Editors of Journal of Biochemistry (2000-2003) and Human Molecular Genetics (2008-). Dr. Sasaki has been the Vice President of the Japanese Society for Epigenetics (2006-).
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Dr. Rakesh Mishra
"Epigenetic regulatory elements and genomic organization in development: an evolutionarily conserved theme from flies to mammals"
Dr Rakesh Mishra, PhD (India) received his D.Phil. (Organic Chemistry, Nucleic Acids Synthesis) in 1986 from the University of Allahabad. He started his carrier in biology by studying non-B DNA conformations and DNA topology at Molecular Biophysics Unit of the Indian Institute of Science, Bangalore, and initiation of transcription at the Centre for Cellular and Molecular Biology, Hyderabad. He used this expertise to extend application of oligonucleotides against protozoan parasites and for knock out of small nucleolar RNAs in Xenopus oocytes to study the role of such RNAs. He then became interested in chromatin organization and decided to take a genetic approach using homeotic gene complex of Drosophila melanogaster at the University of Geneva. He joined CCMB as senior Scientist in March 2001. At CCMB his lab has studied role of chromatin organization in regulation of genes and the epigenetic mechanisms involved in this process (Mole. Cell. Biol. 27, 4796-4806, 2007, BioEssays 28, 445, 2006; Genetics 168, 1371-1384, 2004). Taking biochemical, genetic and comparative genomics approach they revealed the chromatin mediated establishment and maintenance of epigenetic mechanisms. In particular his work has contributed to an understanding how specific Polycomb group proteins are recruited to established epigenetic cellular memory (Mol. Cell. Biol. 26, 1434, 2006; Genes & Dev 19, 1755, 2005; BioEssays 27, 119, 2005; Mech Dev 120, 681, 2003; Mol. Cell. Biol. 21, 1311, 2001; Mol Cell 1, 1065, 1998). Taking a comparative genomics approach, he has identified unprecedented conservation in non-coding regions of vertebrate hox complexes (BMC Genomics, 5, 75, 2004). These elements are turning out to be novel regulatory elements operating on many developmentally regulated genes. Most recent results suggest that these novel elements may be transcribed and that the non-coding RNA product may be the key to these ultra conserved regulatory elements. In order to look for the packaging code in the genome and finding novel functional elements, he has analysed non-coding regions of the human genome (Bioinformatics 19, 681, 2003; Genome Biology 4, R13, 2003; Bioinformatics 19, 549, 2003). In vivo assays have recently shown that several repeats are involved in chromatin-mediated higher order regulatory mechanisms and organization of the genome. In past few years he has presented his work in over 50 international conferences, including European and American Drosophila meetings, Cold Spring Harbour Symposia and Gordon Research Conferences.
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Dr. En Li
"Function of DNA methylation and protein modifications in development and stem cells"
Dr. En Li is currently Vice President of Novartis Institutes for BioMedical Research (NIBR), and Head of the newly established Novartis R&D center in China - NIBR Shanghai. He joined Novartis as Vice President and Global Head, Models of Disease Center and Epigenetics Program in 2003. Prior to that, he was an Associate Professor of Medicine at Harvard Medical School and a faculty member of the Cardiovascular Research Center and Center Cancer, Massachusetts General Hospital. He received a Bachelor of Science degree in Biochemistry from Beijing University in 1984 and a Ph.D. degree in Biology from MIT in 1992. Dr. Li’s an established scientific expert in the field of Epigenetics. While he was at Harvard Medical School, his laboratory discovered a family of DNA cytosine methyltransferases that establish DNA methylation patterns in the human genome and their roles in animal development and human diseases. He also made important contribution to the field of mammalian development. His research interests include cancer genetics and epigenetics, stem cell biology, and TGF-ß and BMP signaling in mammalian development. He has published more than 100 research papers and review articles in major scientific journals.
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Henk Stunnenberg
"Time-lapse of gene expression and histone modifications during differentiation "
Prof. Dr. Stunnenberg was appointed in 1996 as full professor and head of the Department of Molecular Biology and has appointments at the Science and Medical Faculty, University Nijmegen, The Netherlands. He is the founder and main organizer of the biennial EMBL meeting on transcription and a member of EMBO since 1992. He was a group leader at the EMBL gene expression program from 1985 to 1996, Heidelberg where he studied regulation of gene expression at the transcription factor level and in particular the action of nuclear receptors. He was amongst the first to identify the oncogene v-ErbA as a dominant negative transcription factor, to identify a Retinoic Acid Receptor Response element, and RXR as the heterodimer partner. He has also contributed very significantly to deciphering basal transcription processes.
More recently his group has turned its attention to the role of chromatin and chromatin-associated factors in gene regulation during development, differentiation and disease.He is the coordinator of the EU-FP6 Integrated Project HEROIC which focuses on Epigenetic Regulatory Organisation In Chromatin of mouse Embryonic Stem cells. His group is performing high accuracy and high-throughput mass spectrometry approaches are used in complex-walking and examination of post-translational modification, to identify and characterize protein complexes that write, read and interpret the histone code; DNA methylation profiling at high resolution (MeDIP-on-chip) and ChIP-Solexa profiling.
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Huck-Hui Ng, Ph.D
"Transcriptional regulatory network in ES cells"
Huck-Hui Ng, PhD Sr. Group Leader, Stem Cell and Developmental Biology group of Genome Institute of Singapore. Dr Ng’s research interest is to understanding the mechanisms underlying self-renewal and pluripotency of embryonic stem cells. Dr. Ng received his BSc from National University of Singapore and PhD. from University of Edinburgh under the supervision of Adrian Bird. During that time, he and other co-workers discovered the link between methyl-CpG binding proteins and histone deacetylases. He then carried out his postdoctoral training at the Harvard Medical School with Kevin Struhl to work on the biological roles of histone modifiers. There after, he joined the Genome Institute of Singapore to setup his laboratory to study transcriptional regulation in stem cells. He and other colleagues identified novel regulators that maintain self-renewal of embryonic stem cells and mapped out the regulatory networks governed by key transcription factors.
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Nuclear architecture: basic and translational perspectives
Rudolf Grosschedl, Ph.D
"Role of histone modifications in transcription and cell lineage regulation"
Rudolf Grosschedl, PhD, Professor and Director of the Max-Planck-Institute of Immunobiology in Freiburg, Germany. Dr. Grosschedl’s research is focused on the regulation of higher-order chromatin structure and the differentiation of hematopoietic stem cells and lymphoid progenitor cells in response to extracellular signals. Dr. Grosschedl also studies the transcriptional responses to Wnt signals. Dr. Grosschedl received his MS degree from Freiburg University, Germany and his PhD degree from Zurich University, Switzerland. After his postdoctoral research at the Whitehead Institute/Massachusetts Institute of Technology, Cambridge, USA, he joined the faculty of the University of California at San Francisco in 1986, where he rose to the rank of full professor. In 1988 he was nominated as a member of the Howard Hughes Medical Institute. In 1999, Dr. Grosschedl moved to the University of Munich to head the Gene Center. In 2004 Dr. Grosschedl was appointed as Director of the Max-Planck-Institute of Immunobiology in Freiburg, Germany. Dr. Grosschedl received several awards and honors, including the scholarship of the Leukemia Society of America in 1987 and he was elected as a member of the European Molecular Organization in 2000. He served on NIH study sections and is member of the editorial boards of Genes & Development (1992-present), Molecular and Cellular Biology (1990-2004) and Immunological Reviews (2002-2004). Since 1999, he serves as member of the advisory board of the biotech company Atugen/ Silence Therapeutics and is on the board of the European Transcriptome, Regulome & Cellular Commitment Consortium, Rotterdam, Netherlands.
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Sung Hee Baek
"Chromatin modifiers in prostate cancer and
metastasis"
Sung Hee Baek, PhD, Associate Professor of Seoul National University. Dr. Baek’s work is focused on the epigenetic regulatory mechanism of cancer metastasis. In addition, Dr. Baek studies transcriptional regulatory mechanism of nuclear receptors and chromatin remodeling complexes in prostate and breast cancer metastasis. Dr. Baek received her BS degree from Seoul National University, and her MS and Ph.D. degrees from the same University. Following her postdoctoral research in Michael G. Rosenfeld’s lab at HHMI, University of California, San Diego, and following research assistant professor at HHMI, she joined the faculty of Seoul National University in 2003, and now works as an associate professor. Dr. Baek received numerous awards and honors, including the 4th L’OREAL-UNESCO for Women in Science Award (2005), the 2nd Macrogen New Investigator Award (2005), The 1st Jin-Pok Kim’s Award for the Best Cancer Research (2006), the 3rd Macrogen for Women in Science Award (2007), and the 3rd AMORE-PACIFIC New Investigator Award (2007). She has been invited as a managing Editor for Frontiers in Biosciences. Please visit web site for further information (http://plaza.snu.ac.kr/~sbaek).
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Rho Hyun Seong, Ph.D
"Role of the SWI/SNF chromatin remodeling complex during early B lymphocyte development"
Rho H. Seong, PhD, Professor and Director of Research Center for Functional Cellulomics, Seoul National University. Dr. Seong’s work is mainly focused on the differentiation of lymphocytes in mouse. Dr. Seong studies the SWI/SNF chromatin remodeling complex in the development of mouse embryo and immune system. Dr. Seong received his BS and MS degrees from Seoul National University, and his Ph.D. degree from Stanford University. Following his postdoctoral research at Stanford University Medical Center, he joined the faculty of Seoul National University in 1993, where he is now a full professor. He founded and directed the Research Center for Functional Cellulomics at SNU. He has served as an associate editor of Korean Journal of Zoology (1997), Korean Journal of Biological Sciences (1999), and Molecules and Cells (2000). He has also served on the Scientific Advisory Boards of International Vaccine Institute. He currently serves as a Secretary General of the 9th International Congress of Cell Biology, which will be held in October 2008 in Seoul.
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Depei Liu, Ph.D
"Epigenetics and regulatory mechanisms of gene clusters"
Depei Liu, PhD, Professor of National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College; Vice President Chinese Academy of Engineering (CAE) and President Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC). He has published approximately 100 articles in international journals. Research interests: Major in Medical Molecular Biology, Research in Gene Regulation of Expression and Gene Therapy, including Gene Regulation of Expression in Differentiation and Development, Gene Transfer and Gene Therapy, Cardiovascular Disease. Social Service and Membership: Member, American Society of Hematology (ASH); Member, Society of Chinese Bio-scientists in America (SCBA) ; Member, Chinese Academy of Engineering (CAE); Member, ASMBE; President, Chinese Society of Biomedical Engineering; President, Beijing Society of Biochemistry and Molecular Biology.
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Edwin Cheung, Ph.D
"Whole Genome Chromatin Interaction Analysis using Paired End diTag Sequencing"
Edwin Cheung, PhD, Senior Research Scientist, Genome Institute of Singapore. Dr. Cheung’s work is focused on elucidating the molecular basis by which steroid hormones control the development and progression of human cancers. Specifically, he is interested in applying modern biological approaches to define the rules governing signal-regulated gene expression by steroid hormones (estrogen and androgen), their cognate receptors and associated cofactors. Dr. Cheung received his bachelor’s degree from UC Berkeley. He then obtained his Ph.D. degree from University of Manchester. After his Ph.D., Dr. Cheung received a Susan G. Komen Breast Cancer Foundation postdoctoral fellowship and an NIH postdoctoral fellowship to perform his postdoctoral research at Cornell University. Following his postdoctoral work, he moved to Singapore and started his own group at the Genome Institute of Singapore.
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Chia-Lin Wei
"Global Mapping of Chromatin Interactions
Mediated by Epigenetic
Modifications in Murine ES Cells"
Chia-Lin Wei, Sr. Group Leader, Genome Technology & Biology Group of Genome Institute of Singapore. Dr. Wei’s research interest is to characterize the impacts of epigenetic modifications and chromatin structures on gene expression program in embryonic stem cells by applying ultrahigh throughput next generation sequencing platform. Dr. Wei received her BS from Yang Ming University, Taiwan and Ph.D. from University of California, Davis. She continued her postdoctoral training in Massachusetts Institute of Technology, studying Drosophila development and apoptosis. In 1998, she moved to Large Scale Biology Incorporation, California where she built up the full length cDNA library capacity for EST sequencing and functional genomic program. She joined Genome Institute of Singapore in 2002 and is responsible for establishing the genome technology platform and genome biology program. During the last 5 years, she and her colleague, Ruan Yijun, have developed the pair end ditag (PET) sequencing approach and pioneered in using the sequencing approach to interrogate the stem cell genomes for their functional units, transcription networks and architectures. The PET technology has been adapted to decipher the epigenome and nuclear organization and Dr. Wei was one of the recipients for 2006 Singapore National Science Award.
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David M. Gilbert, PhD
"Chromasome replication and nuclear reprogramming during stem cell differentiation"
David M. Gilbert, PhD is J. Herbert Taylor Distinguished Professor of Molecular Biology in the Department of Biological Sciences at Florida State University. Dr. Gilbert’s work focuses on the mechanisms regulating DNA replication during the cell cycle and the relationship between DNA replication and structural and functional organization of chromosomes, most recently during differentiation in human and mouse embryonic stem cells. Dr. Gilbert received his BA degrees in Biochemistry/Cell Biology and Philosophy from the University of California at San Diego and his PhD in Genetics from Stanford University. He did two post-doctoral training periods, first as an EMBO Fellow with Pierre Chambon in Strasbourg, France studying transcriptional control and second as a Roche Fellow with Melvin DePamphilis studying replication origin recognition. He joined the faculty at State University of New York (SUNY) Upstate Medical University in 1994 and was appointed Full Professor in 2003. In 2006, he moved to Florida State University for his current Endowed Chair position. Dr. Gilbert’s awards include the American Cancer Society Junior Faculty Research Award (2000), the SUNY President’s Young Investigator Award (2002) and the NIH Career Enhancement Award for Stem Cell Research (2004). He has served on American Cancer Society (1996-2004) and NIH study sections (1997-present) and is an editorial member of the Epigenetics Society.
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Zhi-hu Zhao, PhD
"Reprogramming of poised chromosomal interaction networks upon differentiation of embryonic stem cells"
Zhi-hu Zhao, PhD, Group Leader, Associate Professor of Beijing Institute of Biotechnology. He started his carrier by studying the zinc-finger protein-DNA interactions. He received his BS degree from Wuhan University, and his MS and PhD. from Academy of Military Medical Sciences (AMMS), Beijing. He did his postdoctoral research at Rolf Ohlsson’s lab and switched his research to epigenetics. Dr. Zhao is currently interested in chromosome interactions and 4D gene regulation.
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DNA methylation: basic and translational perspectives
Stephan Beck
"High-throughput Approaches for DNA Methylation Profiling"
Stephan Beck is Professor of Medical Genomics at the University College London (UCL) Cancer Institute. Using experimental and computational approaches, his laboratory has broad interest in the (epi)genomics of phenotypic plasticity involved in differentiation, epistasis and disease. He received his PhD in 1985 from the University of Konstanz where he studied DNA structure. After appointments at the MRC Laboratory of Molecular Biology in Cambridge, Millipore Corporation in Boston and the Imperial Cancer Research Fund in London, he joined the Sanger Institute in 1996. During his tenure as Head of Human Sequencing (1998-2006), he contributed to the sequencing and analysis of the human, mouse and zebrafish genomes. He is a co-founder of the Human Epigenome Project (www.epigenome.org).
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Toshikazu Ushijima, MD, PhD
"Formation of epigenetic field for cancerization by environmental factors"
Toshikazu Ushijima, MD, PhD, Chief of Carcinogenesis Division, National Cancer Center Research Institute (NCCRI), graduated from University of Tokyo School of Medicine in 1986. He started his research career at NCCRI in 1989. He developed one of the first genome-wide screening techniques for changes in DNA methylation, methylation-sensitive-representational difference analysis, in 1997. Contrary to what people tended to think of, he enriched unmethylated fractions of the genome and performed subtraction to isolate genes methylated in cancers. This strategy eluded interference by repetitive sequences, and his team identified many genes aberrantly methylated in various human cancers. In gastric cancers, a novel tumor-suppressor gene, LOX, was identified. During the process, his team noticed that a small amount of aberrant methylation was present even in non-cancerous gastric mucosae of cancer cases. The team proceeded to show that levels of aberrant methylation in non-cancerous gastric mucosae correlated with a risk of cancer development. It was also shown that Helicobacter pylori infection strongly induced aberrant methylation of many, but specific, genes. It was indicated that exposure to some types of carcinogens induces a field defect for cancers that can be detected by aberrant DNA methylation. In neuroblastomas, his team revealed that methylation of multiple CpG islands, CpG island methylator phenotype (CIMP), was tightly associated with a poor prognosis. CIMP was shown to be more informative than many other molecular markers previously developed, and useful even among the cases in advanced stages without N-myc amplification.
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Qian Tao
"Genome-wide epigenetic identification of novel tumor suppressor genes"
Associate Professor of the Department of Clinical Oncology, Chinese University of Hong Kong (CUHK) and Director of the Cancer Epigenetics Laboratory, State Key Laboratory in Oncology in South China, CUHK. Dr. Tao’s major interest is cancer epigenetics - the identification of novel tumor suppressor genes silenced by promoter CpG methylation in common tumors through integrative epigenetics and genomics, and the functional characterization of these novel genes. Dr. Tao received his BS degree from Hunan Normal University, and the Ph.D. degree from the University of Hong Kong. Following his postdoctoral research at the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, he joined the faculty of Department of Oncology, Johns Hopkins School of Medicine in 1999. He led the Cancer Epigenetics Laboratory at the Johns Hopkins Singapore research center from 1999-2004. Dr. Tao moved to CUHK as an Associate Professor in 2004. Dr. Tao received several awards including the Dr. KP Stephen Chang Gold Medal for the Best PhD thesis (1995/96), Faculty of Medicine, University of Hong Kong. He has published over 60 papers in international journals, including Lancet, Blood, JCO, HMG, Oncogene and PNAS. He is a Panel member of Reviewers for key project grants of the Natural Science Foundation of China, and an external reviewer for several grant agents including the Medical Research Council UK, the Wellcome Trust, the Research Grants Council of Hong Kong, and the National Medical Research Council of Singapore. He also serves as a reviewer for multiple scientific journals including Lancet, HMG, Oncogene, MCB, AJP and Blood. He is a vice-President of the Epigenetics Society and an active member of AACR and the International Association for Research on EBV and Associated Diseases.
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Jingde zhu, Ph.D
"Basic and translational cancer epigenetics
(-omics): from DNA methylation perspectives"
Jingde Zhu (Ph.D), Professor and P.I. of the Cancer Epigenetics and Gene Therapy group in the State-key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Jiaotong University since 2001. His major current research interests in both fundamental and translational aspects of cancer epigenetics(-omics), DNA methylation and small noncoding RNAs in particular. His team is also actively developing the novel tumor targeting approaches at the transcription level for cancer gene therapy. His current research is supported by the grants from the national and local governments as well as the European 6th frame program. In addition to a new robust approach to the genome-wide DNA methylation of liver cancer and bladder cancer, his team has also been establishing the DNA methylation based staging and classification system of liver cancer and explore the clinical utility of DNA methyaltion for cancer detection and chemo-sensitivity prediction. In 1985, He obtained Ph. D concerning the functional role of the chromatin structure in gene transcription in Beatson Institute for Cancer Institute in Glasgow. After a brief post-doctor training in Beaston Institute and Washington University in St Louis, he took the P. I position at an associated professor level in Shanghai Institute of Cell Biology, Academica Sinica. He worked in three institutes and one biotech company from 1990 to 2001 in UK as the senior scientist and P.I. on the subjects such as the transcription regulation of the lieange specific gene expression in myeloid lineage and the dual control system to selectively drive the therapeutic gene expression in the p53 defective cancer cell lines.
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Young-Joon Kim
"The epigenetic regulation and variability of gene expression"
Young-Joon Kim, PhD, Professor and Director of the Yonsei University Genome Institute. Dr. Kim’s work is focused on the regulatory mechanism of Drosophila and mouse innate immune systems as well as epigenetic regulation of disease-associated gene expressions. Dr. Kim received his BS degree from Seoul National University, and his Ph.D. degree from Stanford University. Following his postdoctoral research at the Roger Kornberg’s laboratory at the Stanford University, he joined the faculty of Samsung Biomedical Research Institute in 1994, and moved to the Yonsei University in 2000 where he rose to the rank of Full Professor. Dr. Kim established the Yonsei Genome Institute in 2007. Dr. Kim received numerous awards and honors, including the The Life Science Research Award from Korean Molecular and Cell Biology Society (2006). He has served on the AACR international human epigenome taskforce team (2004-2005), Review committee member of Human Frontier Science Foundation (2003-2008). He also organized several international congresses as the Chair of the Academic Program Committee in the Federation of Asian and Oceanian Biochemistry and Molecular Biology Conference (2007), and Interantional Cell Biology Congress (2008). He has also served on the Scientific Advisory Boards of several leading research institutions and biotech companies, among other extramural activities.
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Susan Clark
"Epigenetic deregulation in prostate cancer"
Clark Susan, PhD, Prof Susan Clark has a highly acclaimed international reputation for her work in mammalian epigenetics. Susan heads the epigenetics research program at the Garvan Institute of Medical Research in Sydney, Australia. She graduated in 1982 with a phD in Biochemistry at the University of Adelaide and then spent ten years in the Biotechnology Industry before returning to basic research in gene regulation. Her studies over the last twelve years have initiated profound questions about the importance of epigenetics in early development and in disease, especially in cancer. She has made extensive ground-breaking discoveries relating to DNA methylation patterns in normal and cancer genomes, that have led to new tests for early cancer detection. The techniques she pioneered in the early 1990s, including bisulphite sequencing, have revolutionised and now underpin a new era in epigenetics research, namely the Human Epigenome Project.
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Yi-Ching Wang, PhD
"Cigarette-specific carcinogen induces stabilization of DNA methyltransferase 1 through AKT/GSK3β/βTrCP pathway in lung cancer"
Yi-Ching Wang, PhD, is currently a Distinguished Professor of Department of Pharmacology, College of Medicine, National Cheng Kung University, Taiwan. Prof. Wang received her Ph.D. from Genetic Program of Michigan State University in 1993. She studies the molecular mechanisms involved in lung tumorigenesis. Many evidences show that there are many unique genetic and epigenetic alterations in Taiwanese lung cancer compared to that in other countries. Therefore, Prof. Wang investigates the etiological association of alterations in several tumor suppressor genes, oncogenes, and DNA repair genes with lung tumorigenesis. The alteration analyses include the following aspects: gene mutation and polymorphism, gene loss, hypermethylation of promoter, chromatin structure alteration of gene locus, mRNA alteration, and altered protein expression. More recently, Prof. Wang has continued to do research on cancer genomics and epigenomics such as genome-wide search of loss of heterozygosity of microdissected primary lung tumors, and genome-scanning approaches of DNA methylation and chromatin alteration profiles for identification of new genes critical to lung tumorigenesis. In addition, several potential anti-cancer drugs are developing in her laboratory. Prof. Wang has published more than 40 SCI papers on lung cancer including prestigious journals such as J. Clin. Invest., (SCI 15.754); J. Clin. Oncol., (SCI 13.598); Cancer Res., (SCI 7.656); Oncogenes (SCI 6.585); and Clin. Cancer Res., (SCI 6.177) on lung cancer. Prof. Wang was one of the recipients for Excellent Research Award of Taiwan National Science Council.
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Histone modifications: basic and translational perspectives
Yi Zhang, Ph.D
"Role of histone modifications in transcription and cell lineage regulation"
Yi Zhang, Ph.D. is an Investigator of the Howard Hughes Medical Institute and a Professor of the University of North Carolina at Chapel Hill. Dr. Zhang’s work is focused on understanding the role of epigenetic modifications in gene expression, cell lineage determination, maintenance, and stem cell biology. He is also interested in how dysregulation of the various chromatin modifying enzymes contribute to cellular proliferation and cancer. Dr. Zhang received his BS degree from China Agriculture University, and his Ph.D. from the Institute of Molecular Biophysics at Florida State University. Following his postdoctoral training at the HHMI and Robert Wood Johnson Medical School-UMDNJ, he joined the faculty at the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill in 1999. His group is responsible for identification and characterization of a number of histone methyltransferases and demethylases. Dr. Zhang has received a number of awards, including the Sidney Kimmel Foundation for Cancer Research Scholar Award (2001), the American Cancer Society Research Scholar Award (2003), the Gertrude B. Elion Cancer Research Award from the American Association for Cancer Research (2003), the Ruth and Phillip Hettleman Prize for Artistic and Scholarly Achievement (2004), and the Junior Achievement Award from the Society of Chinese Bioscientists in American (2006).
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Yang Shi, PhD,
"Histone demethylases and dynamic regulation of histone methylation"
Yang Shi, PhD, Professor, Department of Pathology, Harvard Medical School. Dr. Shi’s work is focused on gene regulation and chromatin biology, and throughout his career, Dr. Shi has made numerous fundamental contributions. Dr Shi’s recent breakthrough is the discovery of the first histone lysine-specific demethylase LSD1. Dr. Shi received his BS degree from Shanghai First Medical College (now Fudan University Medical School), and his Ph.D. degree from New York University. Following his postdoctoral research at Princeton University, he joined the faculty of Harvard Medical School in 1991. Dr. Shi is a recipient of the American Cancer Society Junior Faculty Research Award (1994) and the Ludwig Scholar Award (2000). He has served on the NIH study sections (1996-2004) and is currently members of the editorial boards of Mol. Cell. Biol. and JBC. He also served as president of Ray Wu Society (2000-02) and on the grant review panels of the Chinese National Sciences Foundation.
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Yutaka Kondo , MD, PhD (Nagoya, Japan)
"Gene silencing by histone H3 lysine 27 tri-methylation in human cancers"
Yutaka Kondo, MD, PhD, Section Head in Division of Molecular Oncology, Aichi Cancer Center Research Institute. Dr. Kondo’s work is focused on the regulation of gene expression by histone modifications and DNA methylation in human cancers, and the clinical implications of these aberrant changes. In addition, Dr. Kondo studies epigenetic regulation in cancer initiating cells. Dr. Kondo obtained his M.D. and Ph.D. degree from Nagoya City University Medical School in Japan. After his postdoctoral research in the Department of Leukemia at the University of Texas, MD Anderson Cancer center, he joined the faculty of MD Anderson Cancer center in 2004. Dr. Kondo moved to Aichi Cancer Center Research Institute in Japan in 2005. Dr. Kondo received several awards and honors, including the Odyssey Program Outstanding Scientific Research Publication Award (2004). His works accomplished to date highlight the importance of histone modifications in cancers, their relationship with aberrant DNA methylation and gene silencing, and the potential in gene discovery.
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Prof. Tapas K. Kundu
"Chromatin Modifications link to Disease and Therapeutics: Implications of Small Molecule Modulators and Nanoparticles."
Prof. Tapas K Kundu is the group leader of Transcription and Disease Laboratory, Molecular Biology and Genetics Unit (MBGU), Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore, India. Research in Dr.Kundu’s group focuses on the regulation of gene expression (transcription) in humans from the chromatin template with special emphasis on diseases and therapeutics. They are not only elucidating the mechanism of transcription regulation through the epigenetic modifications in humans, but also using this process to invent new generation diagnostics, as well as therapeutics for Cancer, AIDS and Diabetes. Dr. Kundu received his Masters in Biochemistry from University of Agricultural Sciences (UAS), Bangalore and Ph.D degree from Indian Institute Science (IISc), Bangalore, following his Post doctoral research at “National Institute of Genetics”, Japan and also at “The Rockefeller University”, NewYork. He joined JNCASR, Bangalore as Assistant Professor in 1999. Dr. Kundu received several awards and Honors including the highest award in India, “Shanti Swarup Bhatnagar” prize. He has also been elected as fellow of National Academy of Science and Indian Academy of Science, India. Department of Biotechnology, Government of India honored him by “National Bioscience Award”. Significantly, Dr.Kundu has recently, edited a book entitled “Chromatin and Disease” published from Springer press, which has drawn attention of Scientists in the field from all over the world.
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Li-Jung Juan, PhD
"Chromatin modifiers in viral replication and cancer"
Li-Jung Juan, PhD, Assistant Research Fellow of the Genomics Research Center (GRC), Academia Sinica, Taipei, Taiwan. Dr. Juan is interested in functions of chromatin modifiers, especially in viral replication and cancer. She received her BS degree from China Medical College in Taiwan in 1990 and her Ph.D. degree from Penn State University in 1996. She then did her postdoctoral research at National Health Research Institutes (NHRI) in Taiwan and subsequently joined the faculty of the NHRI since 2000. In 2006, Dr. Juan moved to GRC of Academia Sinica, Taiwan. Dr. Juan has served on the International Scientific Committee (ISC) of the Asian Conference on Transcription (ACT) since 2002. She organized and co-chaired the Ninth ACT (ACT IX) at Zhunan, Taiwan, in 2005.
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Dr. Xiaodong Cheng
"Chemistry of Methylation: from Histones to DNA"
Dr. Xiaodong Cheng is a Georgia Research Alliance Eminent Scholar and Professor of Biochemistry at Emory University School of Medicine, Atlanta, Georgia. He was educated in China (B.Sc., Fudan University, 1982) and moved to the USA, where he received a Ph.D. in Protein Crystallography in 1989. He subsequently moved to Cold Spring Harbor Laboratory in 1990, reaching the position of Senior Staff Investigator. It was in Cold Spring Harbor where he began a fruitful research collaboration with Dr. Richard J. Roberts (a Nobel Prize winner in 1993) that led to the discovery of base flipping. In 1997, he moved to Emory and his current work focuses on epigenetic biological methylation.
Dr. Cheng’s group determined the first structure of a protein arginine methyltransferase (2000 EMBO J), the first structure of a histone lysine methyltransferase (2002 Cell), established a switch mechanism of Phe/Tyr (phenylalanine/tyrosine) in controlling the degree of lysine methylation by one, two or three methyl groups (2003 Mol. Cell), and illustrated the transition from nonspecific to specific DNA interaction along the substrate recognition pathway by a DNA methyltransferase (2005 Cell). In collaboration with a group of scientists, Dr. Cheng’s group used elegant structural and biochemical analyses that provide insights into the long-standing question of how imprinted genes are targeted for DNA methylation (2007 three Nature papers). They revealed a novel mechanism of converting patterns of histone methylation into patterns of DNA methylation that mediate the heritable silencing, and the underlying DNA sequences of imprinted genes also contribute to the establishment of heritable methylation patterns. More recently, his group demonstrated that an ankyrin repeat domain bind selectively to mono- and dimethylated lysine 9 of histone H3 (2008 Nature Structural & Molecular Biology).
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Non-coding RNAs: basic and translational perspectives
Haifan Lin, PhD
"The epigenetic role of PIWI proteins and piRNAs"
Haifan Lin, PhD, Professor and Director of the Yale University Stem Cell Center. Dr. Lin’s work is focused on the self-renewing mechanism of Drosophila and mouse germline stem cells as well as human embryonic stem cells. In addition, Dr. Lin studies germline development and cancers related to the malignant proliferation of stem cells. Dr. Lin received his BS degree from Fudan University, and his Ph.D. degree from Cornell University. Following his postdoctoral research at the Carnegie Institution of Washington, he joined the faculty of Duke University Medical School in 1994, where he rose to the rank of Full Professor. He co-founded and co-directed the Duke Stem Cell Research Program. Dr. Lin moved to Yale in 2006 to establish the Yale Stem Cell Center. Dr. Lin received numerous awards and honors, including the American Cancer Society Junior Faculty Research Award (1996), the March of Dimes Basil O'Connor Scholar Research Award (1996), the David and Lucile Packard Fellowship for Science and Engineering (1996), Member of the Connecticut Academy of Science and Engineering (2007-), and the G. Harold and Leila Y. Mathers Award (2007). He has served on the NIH study sections (1998-2005), the International Society for Stem Cell Research (2002-), the Editorial Boards of Cell Stem Cells (2007-) and Stem Cells (2005-), and has been invited as a Featured Editor for Nature Reports Stem Cells. He has also served on the Scientific Advisory Boards of several leading research institutions and biotech companies, among other extramural activities.
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Xiaofeng Cao, PhD
"Small RNA-directed Epigenetic Natural Variation in Arabidopsis thaliana."
Xiaofeng Cao, PhD, Professor of the Institute of Genetics and Developmental Biology, CAS. Dr. Cao received her Ph.D. training in Molecular Biology from Peking University and John Innes Center at Norwich in UK. During her postdoctoral training, she worked with Dr. John Rogers at the Institute of Biological Chemistry, Washington State University and subsequently worked with Dr. Steve Jacobsen at UCLA, where she initiated her studies of DNA methylation and gene silencing in Arabidopsis thaliana. In 2003, she became a professor at the Institute of Genetics and Developmental Biology, CAS. Her lab uses Arabidopsis thaliana and rice as model organisms and tries to understand how different small RNAs were generated and targeted to regulate gene expression and plant development. The lab is also interested in understanding the network of gene expression regulated by histone methylation and acetylation both in Arabidopsis and rice. In 2003, Dr. Cao obtained Outstanding Young Scholar Award from NSFC.
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Yijun Qi
"RNAi in Arabidopsis and Chlamydomonas"
Yijun Qi, Ph.D, Assistant Investigator of the National Institute of Biological Sciences (NIBS), Beijing. He earned his Ph.D degree from Zhejiang University in 2001. From 2001 to 2006, he did his postdoctoral research with Dr. Biao Ding at Ohio State University and subsequently with Dr. Greg Hannon at Cold Spring Harbor Laboratory. He joined the faculty of NIBS in 2006. His lab is interested in the mechanisms and biology of RNAi using Arabidopsis and Chlamydomonas as model systems. His lab is one of the two labs that discovered miRNAs in a unicellular organism. Most recently, his lab published in Cell the mechanism of sorting small RNA into Arabidopsis Argonaute complexes.
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Thomas Jenuwein
" EPIGENETIC CONTROL BY HISTONE METHYLATION"
Over the last 12 years, Thomas Jenuwein (IMP, Vienna) has been focusing on the functional characterization of mammalian chromatin. In seminal discoveries, Thomas Jenuwein and his team identified the first histone lysine methyltransferases (HMTases) and showed that the selective methylation of histone H3 on the lysine 9 position (H3K9) generates a high-affinity binding site for the chromo-domain of the HP1 proteins. These landmark findings established a biochemical explanation for the formation and propagation of silenced chromatin domains and for the functional organization of chromosomes. Together, they represent one of the most important breakthroughs in chromatin research during the last two decades. The discoveries and high-profile publications of Thomas Jenuwein had a major impact for basic and applied research and significantly advanced the entire field of epigenetic control. Based on the characterization of the Suv39h enzymes as the first HMTases, histone lysine methylation has been established as a central epigenetic modification in eukaryotic chromatin. Thomas Jenuwein represents one of the world-leading scientists in modern epigenetic research. Future prospects for this field are exciting. It can be anticipated that research into the biological roles of histone lysine methylation will uncover novel insights into normal and pathological development, will be relevant for chromosome stability and genome integrity and lead to a better understanding of cell lineage plasticity, nuclear reprogramming and the molecular nature of stem cells. Thomas Jenuwein will continue with his research on these topics which are of high medical relevance and promise to provide novel avenues for analysing some of the long-standing mysteries, such as cell-type differentiation, regeneration, aging and cancer.
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Erwei Song
Reduction in let-7 microRNA maintains the stemness of breast tumor-initiating cells
Dr. Erwei Song earned his MD and Ph.D at Sun-Yat-Sen University of Medical Science in 2000. Thereafter, Dr. Song received his postdoctoral training at Essen University Hospital in Germany from 1999-2001, and at Harvard Medical School from 2002-2004. He became instructor of Harvard Medical School in Jan 2004, and went back to Sun-Yat-Sen University in Sep 2004 to set up his own lab. Dr. Song is now professor of breast surgery, National Changjiang Scholar, and vise president of the No.2 Affiliated Hospital of Sun-Yat-Sen University. For the past few years, Dr. Song focused his research work on the studies of RNA interference as a therapeutic approach. His publication “RNA interference targeting Fas protects mice from fulminant hepatitis” in “Nature Medicine” was the first report that siRNAs could be used therapeutically in whole animal disease model, and the results were chosen as representative data in the “Top 10 Scientific Breakthrough of 2003” by Science. To further harness RNAi to treat diseases, he explores different strategies to deliver siRNA into specific cell populations in vivo, and validates suitable disease targets for RNAi therapy. He is first author of the manuscript published in the June issue of “Nature Biotechnology”, entitled “Antibody-mediated in vivo delivery of short interfering RNAs via cell surface receptors”, which demonstrated the value of single-chain antibody to deliver siRNA into specific cell types. The paper was selected as cover story by the journal. Recently at Sun-Yat-Sen University, he led a research team studying the contribution of microRNAs in the stemness of breast cancer initiating cells, and published his findings in “Cell” as corresponding author.
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Zicai Liang
Substrate Specificity of Human RISC
Zicai Liang Institute of Molecular Medicine, Peking University, Beijing 100871, China liangz@pku.edu.cn
RNA interference (RNAi) is a
post-transcriptional gene silencing process whereby double-stranded siRNA knock-downs the expression of homologous mRNA by forming base-pairing interaction with complementary target site on mRNA. Although RNAi is established as a sequence-specific process, extensive unpredictable off-target effects are observed. Therefore, the specificity of RISC (effector of RNAi) is brought up as a critical issue for both mechanism and applications study. To study the specificity of RISC, we have previously examined RNAi efficacies of an active siRNA on all possible single-nucleotide mutated target sites. Here, three additional siRNAs were examined for full site mutation assay. Similar tolerance profiles across target site were observed, which suggests that siRNA target site can be segmented into four regions with different specificity to single-nucleotide mismatch. Subsequently, additional sixteen siRNAs were studied on target sites mutated at 3 positions. To our surprise, consistent yet specific preference was identified at each position, which is independent of siRNA sequence context. More interestingly, our results showed that thermodynamic characteristics of substrate duplex is unlikely counted for the mismatch specificity of RISC, however, similar patterns were observed between RISC activity and the conformation alternation of substrate. Consistent with our earlier report, tolerance of C:A mismatch was observed on most target sites, suggesting it is a common phenomenon in RNAi. Taken together, our results lead to a hypothesis that the compatibility between RISC and substrate duplex determines its activity and RNAi efficacy.