A*STAR Hosts Nobel Laureate and Renowned Stem Cell Expert Professor Shinya Yamanaka

Published: Apr 02, 2013

April 02, 2013 -- Nobel Laureate Professor Shinya Yamanaka to give a lecture on latest progress in stem cell research at Biopolis and share insights on stem cell research with A*STAR scientific leaders.

1. Professor Shinya Yamanaka, Nobel Laureate in Medicine or Physiology 2012, has been invited to speak at Biopolis under the A*STAR Biomedical Research Council Distinguished Visitor Programme (DVP). Professor Yamanaka’s discovery of induced pluripotent stem (iPS) cells in 2006, won him the Nobel Prize and revolutionised the stem cell field. Since then, iPS cells have been used to study cell therapy, disease mechanisms, and new drug developments worldwide. For Professor Yamanaka’s biography, please refer to Annex A.

2. Professor Yamanaka will be giving a scientific lecture today on the recent progress in induced pluripotent stem (iPS) cell research. Stem cells hold enormous potential in healthcare and medical sector as a renewable source of replacement tissues for regenerative medicine therapies. However, strict evaluation methods of selecting good iPS cell source for transplantation are essential to realise the promise of regenerative medicine. Professor Yamanaka will speak about the latest efforts to standardise iPS cells in clinical grade and to construct the basis of iPS cell stock. Details and an abstract of the lecture can be found in Annex B.

3. Stem cell research is one of the key focus areas in A*STAR’s biomedical research institutes and A*STAR scientific leaders and key clinical partners will also have the opportunity to meet with Professor Yamanaka to discuss his experience and views on stem cell research. A*STAR researchers have been making remarkable strides in the stem cell field, from basic research to provide insights into the regulatory networks that drive reprogramming of cells, to harnessing the power of stem cell-based research to target tumours and enhance healing. More details on some recent A*STAR discoveries and developments in stem cell research can be found at Annex C.

4. The DVP provides a platform for scientific leaders in Singapore’s BMS community to interact with renowned scientists worldwide and to foster collaborative links. Previous distinguished scientists hosted under the DVP include Professor Susumu Tonegawa in 2006 (Winner of the 1987 Nobel Prize in Physiology or Medicine), Professor David Naylor (President of University of Toronto), Professor Iain Mattaj (Director-General, European Molecular Biology Laboratory) and Professor Sir John Savill (then Chief Scientist for the Scottish Government Health Directorates, and Vice-Principal and Head of the College of Medicine & Veterinary Medicine, University of Edinburgh, and current Biomedical Sciences International Advisory Council member). Since the inception of the DVP in 2001, over 70 distinguished visitors have visited Singapore.



Annex A – Professor Shinya Yamanaka’s biography

Annex B - Abstract of scientific Lecture on the recent progress in iPS cell research towards regenerative medicine

Annex C – Recent discoveries and developments in stem cell research

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Professor Shinya Yamanaka is the Director of the Center for iPS Cell Research and Application (CiRA) and a Principal Investigator at the Institute for Integrated Cell- Material Sciences, both at Kyoto University. Professor Yamanaka is also a Professor of Anatomy at the University of California, San Francisco, as well as a Senior Investigator at the Gladstone Institute for Cardiovascular Disease (GICD) and the L.K. Whittier Foundation Investigator in Stem Cell Biology at the J. David Gladstone Institutes.

Professor Yamanaka’s research focused on methods to generate cells resembling embryonic stem cells by reprogramming somatic cells. He sought to understand the molecular mechanisms that underlie pluripotency and the rapid proliferation of embryonic stem cells—they can become any type of cell in the body—and to identify the factors that induce reprogramming.

Professor Yamanaka’s discovery that adult somatic cells can be reprogrammed into pluripotent cells with a simple method has had a profound effect on developmental and stem cell biology. By introducing the genes for four transcription factors, he induced the skin cells of adult mice to become like embryonic stem cells, which he called induced pluripotent stem (iPS) cells. This iPS cell technology represents an entirely new platform for fundamental studies of developmental biology. Rather than using disease models made in yeast, flies, mice or other animals, iPS cells can be developed from patients with a specific disease. As a result, they contain a complete set of the genes that resulted in that disease—representing the potential of an almost perfect disease model for studying disease development, new drugs and treatments.

Professor Yamanaka has received many awards and honors, including the Albert Lasker Basic Medical Research Award, the Wolf Prize in Medicine, the Millennium Technology Award, the Shaw Prize, the Kyoto Prize for Advanced Technology, the Gairdner International Award, the Robert Koch Award and the March of Dimes Prize. In 2011, Professor Yamanaka was elected to the U.S. National Academy of Sciences, one of the highest honors available for scientists and engineers. He was awarded the 2012 Nobel Prize in Physiology or Medicine for his discovery of how to transform ordinary adult skin cells into cells that, like embryonic stem cells, can then develop into other cell types.

In 1996, Professor Yamanaka became an Assistant Professor at Osaka City University Medical School. In 1999, he was appointed Associate Professor at Nara Institute of Science and Technology and in 2003, a full Professor. He became a Professor at Kyoto University in 2004. He joined GICD as a Senior Investigator in 2007. Since 2008, he has directed CiRA.

Professor Yamanaka earned an MD from Kobe University in 1987 and a PhD from Osaka City University in 1993. From 1987 to 1989, he was a resident at the National Osaka Hospital. From 1993 to 1996, he was a postdoctoral fellow at GICD.

Annex B

Recent Progress on iPS Cell Research towards Regenerative Medicine

Date: 2nd April 2013

Time: 11.30am

Venue: Auditorium, Level 2, Matrix, Biopolis

Speaker: Professor Shinya Yamanaka, Nobel Laureate in Medicine or Physiology 2012

Induced pluripotent stem cells (iPSCs) were originally generated from mouse and human fibroblasts by retroviral introduction of Oct3/4, Sox2, c-Myc, and Klf4. In addition to fibroblasts, iPSCs can be generated from various somatic cells, such as hepatic cells, gastric epithelial cells, neural cells, dental pulp cells, peripheral blood cells, and cord blood cells. It is becoming evident that iPSCs are similar to embryonic stem cells (ESCs) in morphology, proliferation, gene expression, and pluripotency. Compared to ESCs, iPSCs can be generated from various genetically identified individuals without destroying fertilized eggs, providing better application opportunities in regenerative medicine. Therefore, cell therapy, disease mechanisms, and new drug development have been studied with iPSCs worldwide.

However, reactivation of integrated genes in iPSCs, tumor formation attributed to differentiation-resistant clones, or considerable variation in differentiation ability between iPSC clones has been reported. These events suggest that it is essential to determine the best induction protocol and the best method to evaluate iPSC clones for future clinical applications. To solve these problems, one of our goals is to standardize iPSC technology, providing efficient protocol with proper source and inducing factors, and method for quality control.

Regarding the safety issue of iPSC preparation, we have reported an integration-free method using episomal vectors. In further studies on iPSC induction factors, we discovered that p53 shRNA, Cyclin D1, LIN28, L-Myc and Glis1, which is strongly expressed in the unfertilized egg, as substitute for the oncogene c-Myc. The optimized combination of these factors can establish iPSCs with a high efficiency and quality for clinical applications.

In order to realize the promise of regenerative medicine, it is essential to have strict evaluation method of selecting good iPSC source for transplantation. In iPSC differentiation to neural progenitor cells, we found the ways to distinguish differentiation resistant lines. In addition, we have performed a series of comparison analyses of the global gene expression, DNA methylation and exon sequences, differentiation potential among 49 human iPSC and 10 human ESC lines. While there is no molecular profile to distinguish between ESCs and iPSCs clearly, some iPSCs showed resistant to differentiate into neural cells, causing tumor. We have identified the genes expressed in differentiation resistant lines, which can be used as molecular markers.

Using our integrated knowledge, we are currently aiming to establish the iPSC preparation method in accordance with Good Manufacturing Practice (GMP) in cell processing center (CPC) at the Center for iPS Cell Research and Application (CiRA), Kyoto University, to set the standard of iPSCs in clinical grade, and to construct the basis of iPSC stock from volunteers having specific human leukocyte antigen (HLA).

Annex C

Recent A*STAR discoveries and developments in stem cell research

Putting Singapore on the world-map for stem cell research

The stem cell group from A*STAR’s Genome Institute of Singapore, comprising Professor Ng Huck Hui, Professor Lawrence Stanton, Professor Paul Robson and Professor Lim Bing, was the first in the world to map the gene regulatory networks controlling stem cell functions. Using cutting-edge genomic technologies, the team advanced the critical know-how to maintain embryonic stem cells, and induce them to create a wide range of specialised cell types in the body. Currently, the team is engaged in several collaborative projects with clinicians to engineer different types of tissues for the replacement of diseased or degenerated tissues in the eye, heart, brain and joints. The team has also made significant discoveries on how differentiated cells like skin cells can be reverted to stem cells. Pharmaceutical companies are seeking to collaborate with the team to explore the use of such techniques to create “patient-specific” stem cells from a patient’s own cells to develop tools for drug discovery and for personalised treatment.

Transforming human blood cells into stem cells

Dr Jonathan Loh from A*STAR’s Institute of Molecular and Cell Biology (IMCB) recently became the first in the world to achieve the reprogramming of human blood cells into ES-like induced pluripotent stem (iPS) cells. This is an important step towards the development of more efficient ways of generating patient-specific pluripotent stem cells for clinical transplantation. Currently, Dr Loh is working on using iPS technology to understand human diseases.

Finding a cure for lung cancer

Singapore scientists led by Dr Bing Lim from A*STAR’s Genome Institute of Singapore (GIS) recently identified lung cancer stem cells (tumour-initiating cells) responsible for the promotion of tumour growth and new drug targets for lung cancer. They showed that the enzyme glycine decarboxylase, which contributes to nucleotide synthesis, is elevated in lung cancer stem cells and that it is critical for the ability of these cells to form tumors in vivo. Since glycine decarboxylase does not appear to be generally required for the growth of normal adult tissues, these results raise the possibility that this enzyme could be a target for cancer therapy.

Dr Lim Bing was recently awarded a GlaxoSmithKline (GSK) grant under the Academic Centre of Excellence (ACE) to further his research on lung cancer at the GIS.

Potential drug for deadly brain cancer

Dr Prabha Sampath from A*STAR’s Institute of Medical Biology recently uncovered a secret of tumor stem cell survival, making progress against a devastating brain cancer, called malignant glioma.

The scientists found that the biomarker, miR-138, is highly expressed in cancer stem cells compared to normal neural stem cells. They thus carried out in vitro experiments to deplete miR-138 in these cancer stem cells with a potential drug, antimiR-138, to observe the effect. They found that when miR-138 is depleted, the cancer cells are completely destroyed. This is an important breakthrough as current therapies such as gamma radiation and surgical methods proved to be inadequate in treating these brain tumours, which tend to re-grow from cancer stem cells and become extremely lethal.

Targeting breast cancer using stem cells

Researchers from A*STAR’s Institute of Bioengineering and Nanotechnology (IBN) led by Dr Shu Wang, made a landmark discovery that neural stem cells (NSCs) derived from human induced pluripotent stem (iPS) cells could be used to treat breast cancer. They demonstrated that these cells may be used in combination with a therapeutic gene to cripple tumor growth.

Harnessing stem cells for regenerative medicine

Professor Victor Nurcombe and Professor Simon Cool of A*STAR’s Institute of Medical Biology have developed novel biomolecules, called heparan sulphate (HS), which enhance wound repair and control the renewal of human stem cells to enhance healing and regeneration. Most recently, animal bone fractures in animals have been successfully treated by heparan sulfate therapy, resulting in increased bone regeneration.

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