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  Newsletter Issue 5, 30 September 2013

Gold Sponsors

 

 

STEM CELL SOCIETY SYMPOSIUM 2013

"Early Human Development & Fetal-Maternal Medicine"

18 -19 November

Matrix Building Level 2 & 2M
30 Biopolis Street, Singapore 138671

Silver Sponsors

 

Bronze Sponsors

 

 

 

 

 

 

 

 

 

 

 

 

 

Dear Members, Delegates, Friends, and Colleagues

The Newsletter, Issue 5 is ready!

In this issue we share abstracts, bios and questionnaires of Graham Jenkin from the Monash University, Australia and of Ray Dunn from the Institute of Medical Biology, Singapore with you.

We also would like to highlight a very recent Nature Article published by the Jacob Hanna lab and collaborators. We are pround to be able to present Jacob as one of our pleanry speakers during the symposium.

Reference: Rais Y, Zviran A, Geula S, Gafni O, Chomsky E, Viukov S, Mansour AA, Caspi I, Krupalnik V, Zerbib M, Maza I, Mor N, Baran D, Weinberger L, Jaitin DA, Lara-Astiaso D, Blecher-Gonen R, Shipony Z, Mukamel Z, Hagai T, Gilad S, Amann-Zalcenstein D, Tanay A, Amit I, Novershtern N, Hanna JH. Deterministic direct reprogramming of somatic cells to pluripotency. Nature, 2013 Sep 18. doi: 10.1038/nature12587. [Epub ahead of print].

We are excited about hearing more from Jacob during the symposium!!!!

COUNT DOWN: times flying; only 49 days the opening of the symposium!!!

Updates:

Symposium hotel: For our overseas attendees, we have negotiated a special room rate at the symposium hotel Park Avenue Rochester which is just across the road and in walking distance to the symposium venue. The hotel is also conveniently located close to public transport facilities such as the bus and the MRT networks. Considering staying in this hotel? Click here for more information.

Delegate Networking Event: We are pleased to announce that a networking event open to all delegates of the symposium will take place on the first evening (18th November). Venue is the Epicentre at Biopolis. Drinks and food will be served to stimulate interactions and communications among delegates.

DEADLINES

Poster Abstract Submission:

Note that the poster submission deadline has been extended to: 8th October 2013.

IMPORTANT: Online Registration Closes:

4 November 2013

Poster abstracts can be submitted during your online registration until 8th October 2013.

 

To register and submit your poster abstract, click HERE.

To learn more about the symposium, follow this LINK.

Contact us HERE.

With best regards,

The Organizing Committee Stem Cell Society Singapore Symposium 2013

Featured Speakers  

Graham JENKIN

Monash University, Australia

 
Abstract  
Use of gestational tissue derived cells for lung and brain repair in neonates

 

Cells with stem cell-like characteristics and capabilities can be obtained from gestational tissues and blood, including the umbilical cord, cord blood, placenta and amnion. We have investigated the potential use of human amnion epithelial cells (hAEC), derived at term caesarean section, and autologous umbilical cord blood mononuclear cells (UBC) for the treatment of premature birth and of birth asphyxia in neonates suffering from respiratory distress and brain injury. hAEC possess multipotent differentiation capacity, low immunogenicity and anti-inflammatory properties. They show both protective and reparative effects when administered at the time of, and immediately following, ventilation induced lung and brain injury. The reparative effects are independent of functional differentiation, acting via inhibition of inflammation and immunomodulation through interaction

with macrophages and T cells to induce resolution of inflammation and fibrosis. Severe birth asphyxia can also result in significant brain inflammation and injury, leading to cerebral palsy in surviving infants. UBC contain populations of cells that also possess anti-inflammatory properties that have the potential to reduce neuropathology. We have demonstrated that administration of autologous UCB to newborn lambs, following severe birth asphyxia, improves behavioral outcomes, brain MRS N-acetyl aspartate/lactate ratio and reduces brain inflammation and neuronal cell death. We are now investigating which components of cord blood are responsible for the efficacious effects observed. The use of hAEC and UCB are attractive sources of cells for the derivation of pluripotent cells for clinical application.

Biography PubMed

 

Professor Graham Jenkin holds a Personal Chair and is a Professor in the Monash Department of Obstetrics and Gynaecology at Monash University. He is Deputy Director of The Ritchie Centre at the Monash Institute of Medical Research. Research currently being undertaken by his group includes clinical translation research into the maintenance of fetal and neonatal wellbeing, including studies on intra-uterine growth restriction, fetal hypoxia, birth asphyxia, infection and premature labour. Preclinical and clinical trials of the use of potential protectants against fetal and neonatal free radical induced brain, lung and kidney damage are being undertaken. The effect of glucocorticoids in treatment of respiratory distress in premature labour and in the growth

restricted fetus are key areas of interest. Research interests also include the use of placental and adult mesenchymal stem cells for treatment of chronic obstructive pulmonary disease, cystic fibrosis, brain neurotrauma and spinal disk injury. His publication record includes over 160 papers 8 patent applications, 31 invited book chapters/journal review articles including editing of 5 International Journal Symposia publications. His contribution to undergraduate and postgraduate student teaching has been recognised with the receipt of the Vice Chancellor’s Award for Postgraduate Supervision. His promotion of linkages with industry was also recognised by the Vice Chancellor’s Award for Excellence in Research Innovation and Collaboration in Research with Industry.

Interview  
What was the first phenomenon you can recall that fascinated you to do science?

Invasion of the Great Barrier Reef in Australia by the Crown of Thorns Starfish.

What is your most memorable career achievement?

Discovery of the characteristics of artificial surfactant for use in the treatment of Bronch Pulmonary Displasia of neonatal infants.

What attracted you to a career in Science?

Studying biology at school followed by working for inspirational scientists during my PhD and Post Doctoral years.

Who are your scientific heroes/role models and why?

Alan Trounson. Colleague and mentor. Thinks outside the box and made huge contributions to reproductive science through pioneering work on IVF and stem cells.

Professor Mont Liggins and Professor Geoffrey Thorburn for their work on fetal physiology that led to benificial clinical translations.

Which scientist/clinician has made the biggest impact in your field and why?

Professor Mont Liggins, discovery of effect of corticosteroids on maturing lungs of premature babies.

What influenced you to pursue stem cell research?

Working with Professor Alan Trounson during the early years of embryonic stem cell research.

Working with Professor Euan Wallace on the use of amnion epithelial cells in the treatment of a range of inflammatory diseases.

What are the main issues confronting stem cell researcher?

Translation of their work into clinical practice. Understanding the mechanisms of action of stem cells when used clinically. Safety and ethical issues of their use. Uncontrolled use of stem cells clinically before undergoing rigorous clinical trials.

Which is the single most factor driving or inhibiting the broad clinical application of stem cells?

Demonstrated safety and efficacy, cost of therapy.

What do you think about stem cells as a business model?

Personalised medicine is not a good model. Autologous use from stem cell banks of cells that are immune tolerant would make a good model.

What would you be if not a scientist/clinician?

An academic or a farm worker.

What's the best advice you ever had?

Don’t burn your bridges. Never make enemies of people, you mever know when it might come back to bite you.

What's the worst advice you ever had?

Study advanced mathematics at school because it would be useful for getting into a career in science. I was NOT good at maths!

What’s your motto in life?

Enjoy what you do. There is no point in working hard unless you are enjoying your work.

Where do you think stem cell research will be with regards to clinical application in 5-10 years’ time?

Definitely will be in clinical use for a variety of clinical applications for intractible diseases. Note that “stem cells” (haematopoietic) have been used clinically for 50 years and there are already Phase 1,11 & 111 clinical trials on use of stem cells, particularly adult (MSC) being undertaken now.

What is the most promising direction in stem cell research?

Prevention of rejection of stem cells used in clinical trials.

What would you tell a student asking you for advice whether to pick up a career in the stem cell field?

A good time to enter the field both for basic and clinical translation research as well as commercialisation.

Your banner could be here. Contact us.

Ray DUNN

Institute of Medical Biology, Singapore

 

 
Abstract  
Master transcription factors controlling human pancreatic development  

Loss-of-function mutations in the transcription factor gene PDX1 are associated with pancreatic agenesis—a rare human condition that occurs when the pancreas fails to develop before birth.  In the mouse and human embryo, PDX1 expression identifies the pancreatic buds as they emerge from the foregut endoderm. This early expression along with the catastrophic developmental consequences of its loss has christened PDX1 as a master transcriptional regulator of pancreas formation.  To simulate the early commitment to the pancreatic lineage, we have developed an in vitro differentiation platform that converts pluripotential human embryonic stem cells (hESC) into proliferating PDX1+SOX9+ progenitors, and have used both microarray approaches and ChIP-Seq to identify PDX1 target genes that putatively govern the earliest stages of pancreatic outgrowth and morphogenesis. 

These studies surprisingly revealed that PDX1, which is generally thought to be a transcriptional activator, is enriched at genes typically associated with liver formation such as AFP, TTR and ALB.  These findings suggest that during development PDX1 simultaneously promotes commitment to the pancreatic lineage while suppressing liver fate.  Indeed, we find that PDX1 overexpression directly suppresses liver genes in hepatocyte cell lines and in hESC stably overexpressing PDX1.  These observations thus provide mechanistic insight into the partial “transdifferentiation” from liver to pancreas previously reported when PDX1 is overexpressed in the adult mouse liver in vivo. Taken together, our findings begin to unveil how the highly focal expression of PDX1 within the early foregut endoderm initiates the pancreas-specific transcriptional program.

Biography PubMed  

Dr. Ray Dunn obtained his Ph.D. in Cell Biology in 1999 from Vanderbilt University Medical Center, Nashville, Tennessee under the supervision of Brigid Hogan, Ph.D., FRS. His thesis described how the TGFb-related growth factor Bmp4 controls primordial germ cell formation in the early mammalian embryo. He then completed a post-doctoral fellowship in the laboratory of Elizabeth Robertson, Ph.D., FRS at Harvard University in Cambridge, Massachusetts, where he studied the growth factor Nodal and its intracellular effector proteins Smad2 and Smad3 during early axis formation and early germ layer patterning in the mouse.In 2004, he joined ES Cell International Pte. Ltd. as a Research Scientist in the Diabetes

Group, eventually being named Program Manager in 2005.

In July 2007, he was appointed as a Principal Investigator in the A*STAR Institute for Medical Biology (IMB) and became an Adjunct Assistant Professor at the Lee Kong Chian School of Medicine at Nanyang Technological University (NTU) earlier this year.  Currently, his lab focuses on the differentiation of human pluripotent stem cells toward the definitive endoderm, the parental lineage of the pancreas, and the role of “master” transcription factor genes such as PDX1 and GATA6 in the formation of glucose-sensing, insulin-secreting pancreatic beta cell.

Interview  

What attracted you to a career in Science?

The simple and obvious fact that everyday is a new day, with the ability to learn and discover.  Even when experiments fail—when cloning takes forever or stem cells fail to cooperate—, there’s the constant march forward, working toward a result and verring away from the dull trap of routine.

What paper(s) had the most influence on you and why?

In early 1994, as a student at the Université Joseph Fourier in Grenoble, France, I was required to choose a paper to present as part of my Developmental Biology class.  I thumbed through the December 1993 issue of Cell and discovered a trio of now very famous papers charcterizing the vertebrate homologs of the Drosophila hedgehog gene. I was immediately fascinated by the newly discovered roles of Hedgehog in controling such diverse developmental process as limb development and patterning of the CNS. My presentation to my class went quite well, despite my French, and I started to read the primary literature more avidly. I discovered a paper in the very next issue of Cell describing the role of the transcription factor Hnf3 (Foxa2) during floor plate development. After contacting the senior author by e-mail (yes, we had e-mail in 1994!), she tentatively agreed to become my thesis advisor. And, so began my journey back to the USA.

What influenced you to pursue stem cell research?

Embryonic stem (ES) cells and I are old friends. My Ph.D. lab was helmed by Dr. Brigid Hogan, who helped to pioneer the use of mouse ES cells to introduce targeted mutations into the mouse germline to study their effects on embryonic development. Her lab was quite large (and daunting) when I first joined, and it seemed like every month a new and fascinating mouse mutant debuted in lab meeting. I too could hardly contain my own excitement (and experimental relief) when my first targeted mutation in the Bone Morphogenetic Protein 4 (Bmp4) gene went germline. As a a student, I also derived several ES cells lines directly from blastocysts and differentiated them in vitro. Even my mother gasped, “That’s really cool,” when she saw a beating group of differentiated cardiomyocytes down the microscope. I totally agreed with her, and my fascination with stem cells and their ability to model developmental processes has endured to this day.

What are the main issues confronting stem cell research?

I just returned from the ISSCR regional forum “Stem Cells in Translation.” The “vibe” at the meeting, which is often promulgated by the mainstream media, was that the pace of stem cell research remains painfully slow—with the perennial complaint of over-promise and under-delivery. Introducing efficacious stem cell therapies into the clinic has been admittedly slow and menaced by high-profile terminations of “first-in-man” trials (e.g. Geron). Thus, it’s a challenge for established and young investigators to maintain their enthusiasm and scientific tenacity—their focus on getting the basic research right before moving into the clinic—when both funding bodies and the public demand lightning fast experimental results.

What do you think about stem cells as a business model?

In principle, I have no reservations about the commercialization of stem cell therapies. I was in fact first recruited to Singapore to join a small biotech company called ES Cell International whose goal was to bring human ES cell (hESC)-derived products to the clinic. Our company’s scientific progress was agonizingly slow and costly, and we were also confronted with daunting manufacturing and regulatory hurdles. Despite our lack of success, other companies such as Advanced Cell Technologies (ACT) have made tremendous progress. ACT has already begun a Phase I/II clinical trial using hESC-derived retinal pigmented epithelial cells for the treatment of age-related macular degeneration—a disease that affects about 30 million people worldwide. ACT’s success in the clinic would most certainly energize and embolden the stem cell field.

In contrast, I have a couple of friends who were injured playing sports in Singapore and, who despite my protestations, journeyed to Malaysia and Thailand for autologous infusions of their own “stem cells.” These unregulated and unproven treatments are costly and often carried out by dubious physicians. The outbreak of such stem cell-based medical tourism frightens me, and there are well-documented cases of where such therapies violate primum nil nocere (“First, do no harm”). Thus, it’s extremely important for us scientists to share with our friends and family—whoever will listen—our concerns about such rogue clinics and publicize go-to, on-line resources such as the ISSCR website that aim to educate the public about stem cells and their legitimate therapeutic uses.

What would you be if not a scientist/clinician?

Probably an editor at a scientific journal. I quite enjoy reviewing papers and have served on the Editorial Board of Development since 2010.

What’s your motto in life?

Maximize your happiness and minimize your grief.

What will be the next major breakthrough in stem cell research?

Brain repair using stem cells remains in my opinion the holy grail. Recent reports on the use of stem cells to restore memory and learning in mice are encouraging, and there are even efforts to model psychiatric disorders like schizophrenia using human induced pluripotent cells (hiPSC). Lastly, at the meeting I just attended in Florence, there was exciting work presented by Lorenz Studer about the use of hESC-derived dopaminergic neurons for the treatment of Parkinson’s disease.