SCSS Young Investigators' Symposium 2017
organized by young stem cell investigators for young investigators
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EVENT DESCRIPTION
The biannual Young Investigators’ Symposium offers PhD and postdoctoral stem cell biologists the opportunity to share their findings with the local research community. Supported by the Stem Cell Society Singapore (SCSS), the symposium aims to reflect the diversity of stem cell research taking place in Singapore today, covering diverse topics including disease modelling, directed differentiation, organoids and reprogramming.
In addition to up and coming local speakers, the program includes keynote presentations from internationally renowned researchers Dieter Egli and Cedric Bardy, and a careers session featuring discussions with scientists working outside academia.
We will end the day with refreshments and the opportunity to network with like-minded colleagues.
Please join us on October 3rd 2017 at level 4 Matrix, Biopolis.
The biannual Young Investigators’ Symposium offers PhD and postdoctoral stem cell biologists the opportunity to share their findings with the local research community. Supported by the Stem Cell Society Singapore (SCSS), the symposium aims to reflect the diversity of stem cell research taking place in Singapore today, covering diverse topics including disease modelling, directed differentiation, organoids and reprogramming.
In addition to up and coming local speakers, the program includes keynote presentations from internationally renowned researchers Dieter Egli and Cedric Bardy, and a careers session featuring discussions with scientists working outside academia.
We will end the day with refreshments and the opportunity to network with like-minded colleagues.
Please join us on October 3rd 2017 at level 4 Matrix, Biopolis.
ABSTRACT
Dr. Egli’s group performs studies on mitochondrial replacement, beta cell replacement, and genetic instability during cell type transitions. A central goal of his group is to better understand the differences in the duplication of the DNA between different cell types, and how these differences affect genetic stability. A novel concept emerging from these studies is that cell-type specific DNA replication provides a quality control system for cell proliferation, providing a key barrier to the growth of cells undergoing abnormal transformations.
BIO-SKETCH
Dieter Egli obtained his PhD degree from the University of Zurich, Switzerland, and trained as a postdoctoral fellow at Harvard University. He then joined the New York Stem Cell Foundation Research Institute, conducting work on somatic cell reprogramming in human eggs. He joined Columbia University as a faculty in 2014 to develop cell therapies for diabetes and to better understand how beta cells fail.
Dr. Egli’s group performs studies on mitochondrial replacement, beta cell replacement, and genetic instability during cell type transitions. A central goal of his group is to better understand the differences in the duplication of the DNA between different cell types, and how these differences affect genetic stability. A novel concept emerging from these studies is that cell-type specific DNA replication provides a quality control system for cell proliferation, providing a key barrier to the growth of cells undergoing abnormal transformations.
BIO-SKETCH
Dieter Egli obtained his PhD degree from the University of Zurich, Switzerland, and trained as a postdoctoral fellow at Harvard University. He then joined the New York Stem Cell Foundation Research Institute, conducting work on somatic cell reprogramming in human eggs. He joined Columbia University as a faculty in 2014 to develop cell therapies for diabetes and to better understand how beta cells fail.

Joel TAN
IMCB, A*STAR
Regulation of spermatogenic stem cells
IMCB, A*STAR
Regulation of spermatogenic stem cells
ABSTRACT
As the role of epigenetics in spermatogenesis becomes more apparent, scientists are beginning to find correlations between epigenetic defects and male infertility. Tripartite motif-containing 28 (TRIM28) is a prominent epigenetic transcriptional co-regulator that has been shown to regulate numerous biological processes such as cellular differentiation. However, little is understood about the role of TRIM28 in spermatogenesis except that ablating it leads to testicular degeneration in mice. In our laboratory, we observed that Trim28-heterozygous (Trim28Het) male mice became infertile prematurely, pointing to a likely haploinsufficiency phenotype of Trim28. Mating experiments confirmed this observation. As these mice grew older, their testes progressively became smaller compared to the wild type. Histological analysis uncovered an increase in sertoli cell-only tubules, suggesting that the size reduction resulted from the loss of germ cells. Since the degenerative phenotype might be a consequence of systemic Trim28-heterozygosity, we generated and compared germ cell-specific and sertoli cell-specific heterozygotes. We found that halving the amount of TRIM28 in the germ cells phenocopied Trim28Het testes, indicating a germ cell autonomous effect. Survey of the germ cell population in the seminiferous tubules revealed that heterozygous germ cells are progressively lost, beginning with the undifferentiated spermatogonia. Contrary to previous publication, which showed that TRIM28 was only expressed in mid-pachytene spermatocytes to early elongating spermatids, we detected Trim28 expression in undifferentiated spermatogonia. Based on these results, TRIM28 appears to have a function in these early cells of spermatogenesis where the stem cell population resides.
BIO-SKETCH
Joel did his undergraduate studies at the National University of Singapore where he graduated with a BSc (Hons). After which, he was awarded an A*STAR graduate scholarship to pursue his PhD. Joel is currently working in the lab of Dr Daniel Messerschmidt at the Institute of Molecular and Cell Biology, A*STAR. His work revolves around the epigenetic regulator – Tripartite motif-containing 28 (TRIM28), and seeks to understand its role in spermatogenesis.
As the role of epigenetics in spermatogenesis becomes more apparent, scientists are beginning to find correlations between epigenetic defects and male infertility. Tripartite motif-containing 28 (TRIM28) is a prominent epigenetic transcriptional co-regulator that has been shown to regulate numerous biological processes such as cellular differentiation. However, little is understood about the role of TRIM28 in spermatogenesis except that ablating it leads to testicular degeneration in mice. In our laboratory, we observed that Trim28-heterozygous (Trim28Het) male mice became infertile prematurely, pointing to a likely haploinsufficiency phenotype of Trim28. Mating experiments confirmed this observation. As these mice grew older, their testes progressively became smaller compared to the wild type. Histological analysis uncovered an increase in sertoli cell-only tubules, suggesting that the size reduction resulted from the loss of germ cells. Since the degenerative phenotype might be a consequence of systemic Trim28-heterozygosity, we generated and compared germ cell-specific and sertoli cell-specific heterozygotes. We found that halving the amount of TRIM28 in the germ cells phenocopied Trim28Het testes, indicating a germ cell autonomous effect. Survey of the germ cell population in the seminiferous tubules revealed that heterozygous germ cells are progressively lost, beginning with the undifferentiated spermatogonia. Contrary to previous publication, which showed that TRIM28 was only expressed in mid-pachytene spermatocytes to early elongating spermatids, we detected Trim28 expression in undifferentiated spermatogonia. Based on these results, TRIM28 appears to have a function in these early cells of spermatogenesis where the stem cell population resides.
BIO-SKETCH
Joel did his undergraduate studies at the National University of Singapore where he graduated with a BSc (Hons). After which, he was awarded an A*STAR graduate scholarship to pursue his PhD. Joel is currently working in the lab of Dr Daniel Messerschmidt at the Institute of Molecular and Cell Biology, A*STAR. His work revolves around the epigenetic regulator – Tripartite motif-containing 28 (TRIM28), and seeks to understand its role in spermatogenesis.

Chwee Tat KOE
Duke-NUS
Asymmetric division of neural stem cells
Duke-NUS
Asymmetric division of neural stem cells
ABSTRACT
Asymmetric cell division is a conserved mechanism use by various stem cells to uphold an intricate balance between self-renewal and differentiation. Defects in asymmetric division of stem cells can result in various developmental defects including microcephaly or tumor formation. Drosophila larval brain neural stem cells, neuroblasts, have emerged as an excellent system to model asymmetric division of stem cells and stem cell derived tumorigenesis. Through genetic screening, we identified Vibrator (Vib)/ Giotto, a phosphatidylinositol (PI) transfer protein (PITP) as regulator of asymmetric division of neuroblasts. Loss of vib or its lipid binding activity disrupts neuroblast polarity, leading to neuroblasts supernumerary. In addition, Vib physically interacts with non-muscle myosin II light chain protein, Spaghetti squash (Sqh) and regulates its cortical localization in neuroblasts. Furthermore, depletion of PI4KIIIa, a PI4Kinase crucial for plasma membrane PI(4)P biosynthesis, similarly disrupts neuroblasts polarity and neuroblast homeostasis. Collectively, we propose a mechanism involving Vib and PI4KIIIa to regulate plasma membrane PI(4)P, Sqh localization and maintenance of neuroblast polarity and homeostasis. BIO-SKETCH Chwee Tat Koe obtained his B.Sc (First Class) from the National University of Singapore. He completed his PhD in developmental neurobiology from NUS Graduate School for Integrative Science and Engineering (NGS), where he identified an epigenetic regulator complex as suppressor of dedifferentiation in the Drosophila neural stem cells. His research effort has focused on the biology of neural stem cells. Moving forward, he is keen to decipher the mechanisms underlying the diversification of neurons and glia. The overall goals of his research are to determine the unique profile of different neuronal and glial types, and to apply this knowledge to understand and develop models of brain disorders. |

Crystal CHIA
IMB, A*STAR
CRISPR-Cas9 genome editing to study pancreatic agenesis
IMB, A*STAR
CRISPR-Cas9 genome editing to study pancreatic agenesis
ABSTRACT
Heterozygous de novo mutations in GATA6 are the most frequent cause of pancreatic agenesis in humans. In mice, however, a similar phenotype requires the complete loss of Gata6 and a closely related gene Gata4. These recent discoveries provide growing evidence for discrepancies between mouse and human pancreatic development. To elaborate the human-specific requirements for GATA6, we chose to model GATA6 loss in vitro by using both gene-edited and patient-derived pluripotent stem cells (hPSC). These cell lines were then differentiated into the pancreatic lineage. We find that GATA6 heterozygous hPSC show a modest impairment in the formation of the definitive endoderm (DE), the parental germ layer of the pancreas, while GATA6-deficient hPSC fail to enter the DE lineage and divert to a mesodermal fate. Consistent with these results, genome-wide studies show that GATA6 binds and cooperates with EOMES/SMAD2/3 to regulate the expression of cardinal DE genes. The early deficit in DE is accompanied by a significant reduction in PDX1+ pancreatic progenitors and C-PEPTIDE+ beta-like cells. Our data thus position GATA6 as a gatekeeper to early human, but not murine, pancreatic ontogeny.
BIO-SKETCH
Crystal obtained her Bachelor's degree in biomedical sciences from the University of Manchester, United Kingdom. She then perused her PhD under joint supervision of Professor Ludovic Vallier at the Wellcome Trust Sanger Institute in Cambridge, United Kingdom, and Dr Ray Dunn at the Institute of Medical Biology, A*STAR. Her PhD research was focused on developing a human pluripotent stem cells (hPSCs) model for the study of pancreatic agenesis and investigating the role of transcription factor GATA6 in this disease. She is currently a newly joined postdoctoral fellow in Dr Bruno Reversade’s lab at the Institute of Medical Biology, A*STAR.
Heterozygous de novo mutations in GATA6 are the most frequent cause of pancreatic agenesis in humans. In mice, however, a similar phenotype requires the complete loss of Gata6 and a closely related gene Gata4. These recent discoveries provide growing evidence for discrepancies between mouse and human pancreatic development. To elaborate the human-specific requirements for GATA6, we chose to model GATA6 loss in vitro by using both gene-edited and patient-derived pluripotent stem cells (hPSC). These cell lines were then differentiated into the pancreatic lineage. We find that GATA6 heterozygous hPSC show a modest impairment in the formation of the definitive endoderm (DE), the parental germ layer of the pancreas, while GATA6-deficient hPSC fail to enter the DE lineage and divert to a mesodermal fate. Consistent with these results, genome-wide studies show that GATA6 binds and cooperates with EOMES/SMAD2/3 to regulate the expression of cardinal DE genes. The early deficit in DE is accompanied by a significant reduction in PDX1+ pancreatic progenitors and C-PEPTIDE+ beta-like cells. Our data thus position GATA6 as a gatekeeper to early human, but not murine, pancreatic ontogeny.
BIO-SKETCH
Crystal obtained her Bachelor's degree in biomedical sciences from the University of Manchester, United Kingdom. She then perused her PhD under joint supervision of Professor Ludovic Vallier at the Wellcome Trust Sanger Institute in Cambridge, United Kingdom, and Dr Ray Dunn at the Institute of Medical Biology, A*STAR. Her PhD research was focused on developing a human pluripotent stem cells (hPSCs) model for the study of pancreatic agenesis and investigating the role of transcription factor GATA6 in this disease. She is currently a newly joined postdoctoral fellow in Dr Bruno Reversade’s lab at the Institute of Medical Biology, A*STAR.

Owen RACKHAM
Duke-NUS
Controlling the fate of human cells with data-driven biology
Duke-NUS
Controlling the fate of human cells with data-driven biology
ABSTRACT
Yamanaka and colleagues revolutionised the field of regenerative medicine when they discovered a set of four transcription factors that can induce a conversion to pluripotent stem cell upon over-expression in a fully differentiated cell type. However, this discovery and other similar discovery that have followed required both expensive and time-consuming trial and error experimentation to find the correct set of factors. This type of problem is common in modern life sciences where we are faced with large combinatorial problems that are both expensive and time-consuming to complete. To demonstrate how computational biology can ameliorate these problems I will present a predictive computational framework (Mogrify) that is able to predict the factors required to convert between any human cell types by combining gene expression data from the FANTOM consortium with gene regulatory network information to predict the reprogramming factors necessary to induce cell conversion. In total Mogrify has been applied to 173 human cell types and 134 tissues, defining an atlas of cellular reprogramming (Rackham et al, Nature Genetics 2016). This atlas has been able to predict factors that have correctly been able to induce several new cell types via transdifferentiation in vitro and is now being leveraged to find novel treatments to disease.
BIO-SKETCH
Owen began his career as a computer scientist and received an MSc in Artificial Intelligence in 2008 from the University of Birmingham, UK. For his PhD, he turned his attention to the application of machine learning to the emerging data analysis challenges in understanding biological systems. In 2012, he graduated a PhD in Complexity Sciences from the University of Bristol before becoming an MRC career development fellow at Imperial College London. Two years ago he joined Duke-NUS, Singapore as a senior research fellow in the Systems Genetics group and subsequently started his own group in June 2016. Owen’s group uses data-driven network biology in order to discover gene expression perturbations, drugs and small molecules that can reprogram cellular states. Their focus is two-fold: Firstly on understanding the biological mechanisms that underpin cell type and secondly using this understanding to develop novel cell therapies or drugs in genetically characterizable diseases.
Yamanaka and colleagues revolutionised the field of regenerative medicine when they discovered a set of four transcription factors that can induce a conversion to pluripotent stem cell upon over-expression in a fully differentiated cell type. However, this discovery and other similar discovery that have followed required both expensive and time-consuming trial and error experimentation to find the correct set of factors. This type of problem is common in modern life sciences where we are faced with large combinatorial problems that are both expensive and time-consuming to complete. To demonstrate how computational biology can ameliorate these problems I will present a predictive computational framework (Mogrify) that is able to predict the factors required to convert between any human cell types by combining gene expression data from the FANTOM consortium with gene regulatory network information to predict the reprogramming factors necessary to induce cell conversion. In total Mogrify has been applied to 173 human cell types and 134 tissues, defining an atlas of cellular reprogramming (Rackham et al, Nature Genetics 2016). This atlas has been able to predict factors that have correctly been able to induce several new cell types via transdifferentiation in vitro and is now being leveraged to find novel treatments to disease.
BIO-SKETCH
Owen began his career as a computer scientist and received an MSc in Artificial Intelligence in 2008 from the University of Birmingham, UK. For his PhD, he turned his attention to the application of machine learning to the emerging data analysis challenges in understanding biological systems. In 2012, he graduated a PhD in Complexity Sciences from the University of Bristol before becoming an MRC career development fellow at Imperial College London. Two years ago he joined Duke-NUS, Singapore as a senior research fellow in the Systems Genetics group and subsequently started his own group in June 2016. Owen’s group uses data-driven network biology in order to discover gene expression perturbations, drugs and small molecules that can reprogram cellular states. Their focus is two-fold: Firstly on understanding the biological mechanisms that underpin cell type and secondly using this understanding to develop novel cell therapies or drugs in genetically characterizable diseases.

Hai-Tong FANG
IMCB, A*STAR
Histone dynamics during cellular reprogramming
IMCB, A*STAR
Histone dynamics during cellular reprogramming
ABSTRACT
Histone variants play important functions in nucleosome architecture, embryonic development and differentiation. Histone H3 variants have been shown to have important role in embryo development, however, the role of H3 variants in induced cell fate transition was elusive. Here, we investigated the global dynamic changes of H3 variants deposition in different cellular reprogramming systems. We showed that H3 variants maintain the cellular identities of the parental cells by forming a tight regulatory node of multiple downstream genes. Removal of H3 variants or its downstream targets during early phases of reprogramming accelerated the process. Contrastingly, H3 variants deposition on genes associated with the newly reprogrammed cell lineage, which begins during the intermediate phases, is essential as its depletion at the later phase abolished the process. Finally, we revealed that the nucleosome configuration and rewiring processes governing cell fate transitions.
BIO-SKETCH
Haitong Fang is a postdoctoral research fellow under the mentorship of Jonathan Loh at Institute of Molecular and Cell Biology. He graduated with a PhD degree from the Institute of Zoology, Chinese Academy of Sciences (CAS) in 2012. He was awarded the Scholarship for Outstanding Graduates and the Excellent Doctoral Award of Zhu Liyuehua Prize from the Chinese Academy of Sciences. He is currently working on exploring the molecular and epigenetic mechanisms of histone variants on cell fate determination.
Histone variants play important functions in nucleosome architecture, embryonic development and differentiation. Histone H3 variants have been shown to have important role in embryo development, however, the role of H3 variants in induced cell fate transition was elusive. Here, we investigated the global dynamic changes of H3 variants deposition in different cellular reprogramming systems. We showed that H3 variants maintain the cellular identities of the parental cells by forming a tight regulatory node of multiple downstream genes. Removal of H3 variants or its downstream targets during early phases of reprogramming accelerated the process. Contrastingly, H3 variants deposition on genes associated with the newly reprogrammed cell lineage, which begins during the intermediate phases, is essential as its depletion at the later phase abolished the process. Finally, we revealed that the nucleosome configuration and rewiring processes governing cell fate transitions.
BIO-SKETCH
Haitong Fang is a postdoctoral research fellow under the mentorship of Jonathan Loh at Institute of Molecular and Cell Biology. He graduated with a PhD degree from the Institute of Zoology, Chinese Academy of Sciences (CAS) in 2012. He was awarded the Scholarship for Outstanding Graduates and the Excellent Doctoral Award of Zhu Liyuehua Prize from the Chinese Academy of Sciences. He is currently working on exploring the molecular and epigenetic mechanisms of histone variants on cell fate determination.

Phuong Thao LY
Duke-NUS
Neuroblast quiescence and reactivation
Duke-NUS
Neuroblast quiescence and reactivation
ABSTRACT
The balance between quiescence and reactivation of stem cells is critical for tissue homeostasis and tumorigenesis prevention, but the underlying molecular mechanisms are largely unknown. The Drosophila larval neural stem cell (neuroblast) is a powerful model to study reactivation in vivo. Currently, only four pathways are known to regulate neuroblast reactivation intrinsically: (i) Insulin signaling, (ii) Transcription factor Prospero, (iii) Hippo signaling, and (iv) Spindle matrix protein Chromator. Based on a genetic screen, we uncover the highly conserved Culin4-RING E3 ubiquitin ligase complex (also known as CRL4 complex) as a novel regulator for neuroblast reactivation. The loss-of-function of CRL4 core subunits, DDB1 (for DNA-damage-binding protein 1) and Cul4 (for Cullin4), causes reactivation defects. CRL4 likely promotes neuroblast reactivation by its conventional ubiquitin ligase activity because the ubiquitin-ligase-impaired form of CUL4, CUL4K8-1R, fails to rescue reactivation defects of cul4-/- mutants. We also demonstrate that the CRL4 complex functions downstream of insulin receptor in promoting neuroblast reactivation. The identification of the relevant substrate receptors and substrates of CRL4 ligases in neuroblast reactivation is in progress. The highly-conserved nature of CRL4 complex suggests the findings from this study could be relevant to quiescence-reactivation regulation in other organisms, including humans, and be generally relevant to stem cell homeostasis.
BIO-SKETCH
Ly Phuong Thao is a PhD student at Duke-National University of Singapore Graduate Medical School (Duke-NUS), Singapore, from 2014. She received her BSc degree from School of Biological Sciences, Nanyang Technological University (NTU), Singapore. Her current research interests include molecular mechanisms regulating quiescence-reactivation balance as well as tumor suppression in Drosophila melanogaster neural stem cells.
The balance between quiescence and reactivation of stem cells is critical for tissue homeostasis and tumorigenesis prevention, but the underlying molecular mechanisms are largely unknown. The Drosophila larval neural stem cell (neuroblast) is a powerful model to study reactivation in vivo. Currently, only four pathways are known to regulate neuroblast reactivation intrinsically: (i) Insulin signaling, (ii) Transcription factor Prospero, (iii) Hippo signaling, and (iv) Spindle matrix protein Chromator. Based on a genetic screen, we uncover the highly conserved Culin4-RING E3 ubiquitin ligase complex (also known as CRL4 complex) as a novel regulator for neuroblast reactivation. The loss-of-function of CRL4 core subunits, DDB1 (for DNA-damage-binding protein 1) and Cul4 (for Cullin4), causes reactivation defects. CRL4 likely promotes neuroblast reactivation by its conventional ubiquitin ligase activity because the ubiquitin-ligase-impaired form of CUL4, CUL4K8-1R, fails to rescue reactivation defects of cul4-/- mutants. We also demonstrate that the CRL4 complex functions downstream of insulin receptor in promoting neuroblast reactivation. The identification of the relevant substrate receptors and substrates of CRL4 ligases in neuroblast reactivation is in progress. The highly-conserved nature of CRL4 complex suggests the findings from this study could be relevant to quiescence-reactivation regulation in other organisms, including humans, and be generally relevant to stem cell homeostasis.
BIO-SKETCH
Ly Phuong Thao is a PhD student at Duke-National University of Singapore Graduate Medical School (Duke-NUS), Singapore, from 2014. She received her BSc degree from School of Biological Sciences, Nanyang Technological University (NTU), Singapore. Her current research interests include molecular mechanisms regulating quiescence-reactivation balance as well as tumor suppression in Drosophila melanogaster neural stem cells.

Filip LACO
BTI, A*STAR
Small molecule regulators of cardiac differentiation
BTI, A*STAR
Small molecule regulators of cardiac differentiation
ABSTRACT
GSK kinase inhibiting molecules such as CHIR99021 are widely used to induce differentiation towards any mesoderm lineage. However, the results can vary between stem cells lines and culture methods. We investigated how GSK inhibition induces cardia differentiation and are able to show that cell growth and cell cycle changes play a dominant role in small molecule driven differentiation methods. With simple methods we are able to assess stability in pluripotent stem cell cultures to increase reproducibility and predict the differentiation outcome. Moreover, we developed novel small molecule class that is able to direct differentiation to both cardiac and neural differentiation. These molecules targeting simultaneous TFG-b and Wnt signalling pathways and can timely direct the stem cell fate.
BIO-SKETCH
Filip Laco (PhD) completed his MSc. In Germany and Singapore at the National University of Singapore and continued his PhD in Scotland at the University of Strathclyde. He developed tissue engineering constructs for skin, endothelial and lymphatics with adult stem cells to model regenerative processes for wound healing and graft implantations. For his postdoctorate Filip Laco (PhD) developed and tested novel small molecules for pluripotent stem cell differentiation at the Bioprocessing Technology Institute in cooperation with the Institute of Chemical and Engineering Sciences A*Star, Singapore. The project was finalized with the generation of a kinase inhibitor class targeting simultaneous TFG-b and Wnt signalling pathways which are able to induce both cardiac and neural differentiation efficiently. In 2014 he started to develop predictable and reproducible small molecule driven methods for cardiac differentiation that could be translated to large scale bioprocessing. He received the Young Investigator Grant in 2015 to investigate novel markers and methods that could help with the quality control of pluripotent stem cell leading to stem cell therapy.
GSK kinase inhibiting molecules such as CHIR99021 are widely used to induce differentiation towards any mesoderm lineage. However, the results can vary between stem cells lines and culture methods. We investigated how GSK inhibition induces cardia differentiation and are able to show that cell growth and cell cycle changes play a dominant role in small molecule driven differentiation methods. With simple methods we are able to assess stability in pluripotent stem cell cultures to increase reproducibility and predict the differentiation outcome. Moreover, we developed novel small molecule class that is able to direct differentiation to both cardiac and neural differentiation. These molecules targeting simultaneous TFG-b and Wnt signalling pathways and can timely direct the stem cell fate.
BIO-SKETCH
Filip Laco (PhD) completed his MSc. In Germany and Singapore at the National University of Singapore and continued his PhD in Scotland at the University of Strathclyde. He developed tissue engineering constructs for skin, endothelial and lymphatics with adult stem cells to model regenerative processes for wound healing and graft implantations. For his postdoctorate Filip Laco (PhD) developed and tested novel small molecules for pluripotent stem cell differentiation at the Bioprocessing Technology Institute in cooperation with the Institute of Chemical and Engineering Sciences A*Star, Singapore. The project was finalized with the generation of a kinase inhibitor class targeting simultaneous TFG-b and Wnt signalling pathways which are able to induce both cardiac and neural differentiation efficiently. In 2014 he started to develop predictable and reproducible small molecule driven methods for cardiac differentiation that could be translated to large scale bioprocessing. He received the Young Investigator Grant in 2015 to investigate novel markers and methods that could help with the quality control of pluripotent stem cell leading to stem cell therapy.

Junghyun JO
GIS, A*STAR
Mini-Midbrain in a dish: Parkinson’s disease modeling
GIS, A*STAR
Mini-Midbrain in a dish: Parkinson’s disease modeling
ABSTRACT
Pluripotent stem cells (PSCs) can be efficiently differentiate into functional homogenous cell types which are present in human brain. These in vitro generated functional nerve cells enable downstream studies and have an availablilty to model human neurological disease as well as potential therapeutic applications. However, homogenous nerve cells which are generated by conventional two-demenstional (2D) culture system have various limitation to understand the physiology of in vivo brain. Recent advances in three-dimensional (3D) culture systems have led to generate human brain organoids in vitro that recapitulate the function of brain. Due to restriction of accessment to functional human brain tissue, hPSCs have been great cell source to generate human brain organoids which mimic the tissue architecture and cellular interactions. In this talk, I introduce we developed a method to generate human midbrain-like organoids (hMLOs) containing midbrain dopaminergic (mDA) neurons which recapitulate features of human midbrain development. The hMLOs contained distinct multiple layers in developing neuroepithelia and showed global transcriptional profiling that resembles human prenatal midbrain. Strikingly, we detected functional midbrain dopaminergic neurons which are electrophysiologically active and produce dopamine in our 3D hMLOs as well as neuromelanin which is dark and insoluble pigment exist in A9 subtype mDA neurons. Using hMLOs, we are applying for in vitro modeling of Parkinson’s disease (PD) which is caused by the selective and progressive loss of mDA neurons particularly from the substantia nigra pars compacta (SNpc), and PD modeling system using hMLOs provides a new avenue to understand PD pathophysiological mechanism in vivo.
BIO-SKETCH
Jo graduated Hanyang University in Seoul for Bachelor’s degree, he began Ph.D. under the supervision of Prof. Lee Dong Ryul at the Department of Biomedial Science, CHA University in Seoul. He majored in Biomedical Science and studied numerous developmental biology related subjects such as germ cell biology, reproductive physiology, embryology, and stem cell biology. He was interested in somatic cell reprogramming and identified a new reprogramming factor to study how to produce a new iPSC line that can be clinically applied through a direct protein introduction system. After he completed his Ph.D, he came to Genome Institute of Singapore (GIS) as Postdoctoral Fellow. He joined lab of Prof. Ng Huck-Hui who is executive director of GIS and began to study in vitro Parkinson’s disease (PD) modeling using human pluripotent stem cells (hPSCs). A conventional 2D differentiation models involve singular cell types in isolation, which is not reflective of the complex progression of PD involving multiple cell types in the midbrain. For this purpose, he conceived to a new protocol to generate human midbrain-like organoids (hMLOs) from hPSCs that recapitulate features of the midbrain by three-dimensional (3D) culture system. His research has been published in high-impact journals and he keep investigating the mechanisms of PD pathophysiology using hMLOs system.
Pluripotent stem cells (PSCs) can be efficiently differentiate into functional homogenous cell types which are present in human brain. These in vitro generated functional nerve cells enable downstream studies and have an availablilty to model human neurological disease as well as potential therapeutic applications. However, homogenous nerve cells which are generated by conventional two-demenstional (2D) culture system have various limitation to understand the physiology of in vivo brain. Recent advances in three-dimensional (3D) culture systems have led to generate human brain organoids in vitro that recapitulate the function of brain. Due to restriction of accessment to functional human brain tissue, hPSCs have been great cell source to generate human brain organoids which mimic the tissue architecture and cellular interactions. In this talk, I introduce we developed a method to generate human midbrain-like organoids (hMLOs) containing midbrain dopaminergic (mDA) neurons which recapitulate features of human midbrain development. The hMLOs contained distinct multiple layers in developing neuroepithelia and showed global transcriptional profiling that resembles human prenatal midbrain. Strikingly, we detected functional midbrain dopaminergic neurons which are electrophysiologically active and produce dopamine in our 3D hMLOs as well as neuromelanin which is dark and insoluble pigment exist in A9 subtype mDA neurons. Using hMLOs, we are applying for in vitro modeling of Parkinson’s disease (PD) which is caused by the selective and progressive loss of mDA neurons particularly from the substantia nigra pars compacta (SNpc), and PD modeling system using hMLOs provides a new avenue to understand PD pathophysiological mechanism in vivo.
BIO-SKETCH
Jo graduated Hanyang University in Seoul for Bachelor’s degree, he began Ph.D. under the supervision of Prof. Lee Dong Ryul at the Department of Biomedial Science, CHA University in Seoul. He majored in Biomedical Science and studied numerous developmental biology related subjects such as germ cell biology, reproductive physiology, embryology, and stem cell biology. He was interested in somatic cell reprogramming and identified a new reprogramming factor to study how to produce a new iPSC line that can be clinically applied through a direct protein introduction system. After he completed his Ph.D, he came to Genome Institute of Singapore (GIS) as Postdoctoral Fellow. He joined lab of Prof. Ng Huck-Hui who is executive director of GIS and began to study in vitro Parkinson’s disease (PD) modeling using human pluripotent stem cells (hPSCs). A conventional 2D differentiation models involve singular cell types in isolation, which is not reflective of the complex progression of PD involving multiple cell types in the midbrain. For this purpose, he conceived to a new protocol to generate human midbrain-like organoids (hMLOs) from hPSCs that recapitulate features of the midbrain by three-dimensional (3D) culture system. His research has been published in high-impact journals and he keep investigating the mechanisms of PD pathophysiology using hMLOs system.

KEYNOTE II
Cedric BARDY
SAHMRI, Australia
Generation of functional human neurons for understanding and treating brain disorders
Cedric BARDY
SAHMRI, Australia
Generation of functional human neurons for understanding and treating brain disorders
ABSTRACT
New medical research opportunities are arising with the emergence of induced pluripotent stem cells (iPSC) technologies. Patient-derived iPSC can be differentiated into electrophysiologically active neurons and provide practical access to live brain tissue in vitro. However, the reprogramming success rates all the way to mature functional neurons remain highly variable. Such experimental variability creates a major challenge for iPSC models of neurological and psychiatric disorders, which aim to compare brain cells from patients and healthy subjects. In this keynote lecture, Cedric will propose new strategies that combines electrophysiology and single-cell transcriptomics to improve the relevance of these experimental models for drug discovery and translational success.
BIO-SKETCH
Cedric Bardy is an internationally recognized leader in the field of human neural stem cells, and an expert in electrophysiology and single cell genetics. His research efforts are focused on developing in vitro models and new biotechnologies to unravel the effect of neurological disorders at the cellular and molecular level. Cedric obtained his PhD in Medicine from the University of Sydney in Prof Dreher’s Laboratory (2004-2008). He was then awarded the most competitive European Postdoctoral Fellowship (Marie Curie International Outgoing Fellowship), and continued his postdoctoral training overseas in two world-class research institutions: 1) The Pasteur Institute in Paris with Prof Pierre-Marie Lledo on the topic of neurogenesis in the adult brain (2008-2010), and 2) The Salk Institute in California with Prof Fred H Gage in the fields of stem cell neuroscience and genetics (2011-2016). In 2016, Dr Bardy was appointed Assistant Professor (Senior Research Fellow) at the newly established and prestigious South Australian Health and Medical Research Institute (SAHMRI). He is currently directing the Laboratory for Human Neurophysiology and Genetics located at SAHMRI. Dr Bardy also serves as an affiliated Associate Professor to the School of Medicine at Flinders University and as a scientific consultant for several biotech in the stem cell field. Dr Bardy is the inventor of the BrainPhys neuronal medium, which he designed in collaboration with Prof Gage to improve the physiology of neuronal culture (Bardy et al. PNAS 2015). The medium is distributed world-wide, and a rapidly growing number of laboratories is using BrainPhys routinely. Most recently, Dr Bardy and his colleagues also developed a new method dubbed PatchSeq, which combines the analysis of the electrophysiology, RNAseq and morphology of a single cell. Such multimodal profiling provides exceptional insights in the phenotypes of human iPSC-derived neurons (Bardy et al. Molecular Psychiatry 2016).
New medical research opportunities are arising with the emergence of induced pluripotent stem cells (iPSC) technologies. Patient-derived iPSC can be differentiated into electrophysiologically active neurons and provide practical access to live brain tissue in vitro. However, the reprogramming success rates all the way to mature functional neurons remain highly variable. Such experimental variability creates a major challenge for iPSC models of neurological and psychiatric disorders, which aim to compare brain cells from patients and healthy subjects. In this keynote lecture, Cedric will propose new strategies that combines electrophysiology and single-cell transcriptomics to improve the relevance of these experimental models for drug discovery and translational success.
BIO-SKETCH
Cedric Bardy is an internationally recognized leader in the field of human neural stem cells, and an expert in electrophysiology and single cell genetics. His research efforts are focused on developing in vitro models and new biotechnologies to unravel the effect of neurological disorders at the cellular and molecular level. Cedric obtained his PhD in Medicine from the University of Sydney in Prof Dreher’s Laboratory (2004-2008). He was then awarded the most competitive European Postdoctoral Fellowship (Marie Curie International Outgoing Fellowship), and continued his postdoctoral training overseas in two world-class research institutions: 1) The Pasteur Institute in Paris with Prof Pierre-Marie Lledo on the topic of neurogenesis in the adult brain (2008-2010), and 2) The Salk Institute in California with Prof Fred H Gage in the fields of stem cell neuroscience and genetics (2011-2016). In 2016, Dr Bardy was appointed Assistant Professor (Senior Research Fellow) at the newly established and prestigious South Australian Health and Medical Research Institute (SAHMRI). He is currently directing the Laboratory for Human Neurophysiology and Genetics located at SAHMRI. Dr Bardy also serves as an affiliated Associate Professor to the School of Medicine at Flinders University and as a scientific consultant for several biotech in the stem cell field. Dr Bardy is the inventor of the BrainPhys neuronal medium, which he designed in collaboration with Prof Gage to improve the physiology of neuronal culture (Bardy et al. PNAS 2015). The medium is distributed world-wide, and a rapidly growing number of laboratories is using BrainPhys routinely. Most recently, Dr Bardy and his colleagues also developed a new method dubbed PatchSeq, which combines the analysis of the electrophysiology, RNAseq and morphology of a single cell. Such multimodal profiling provides exceptional insights in the phenotypes of human iPSC-derived neurons (Bardy et al. Molecular Psychiatry 2016).

Carine BONNARD
IMB A*STAR
A deleterious recessive mutation in NUAK2 causes absence of brain in humans
IMB A*STAR
A deleterious recessive mutation in NUAK2 causes absence of brain in humans
ABSTRACT
Failure of neural tube closure during embryonic development can result in anencephaly (absence of brain) which is one of the most severe and common birth defects worldwide (5-10 cases in 10,000 live births). To better understand its aetiology and pathogenesis we selected families with recurrent anencephalic foetuses. By whole-exome sequencing, we identified a recessive germline 21 bp in-frame deletion in the NUAK2 gene that segregated with the absence of brain in three foetuses born to consanguineous parents. NUAK2 (a.k.a SNARK) encodes a serine/threonine kinase, a member of the AMPK-related kinase family. In vitro phosphorylation assays demonstrated that the 7 amino-acid deletion in the NUAK2 kinase domain abrogated its kinase activity. Consistent with this being a null allele, a knockout of NUAK2 in mice also caused severe exencephaly (Ohmura et al., 2012). To further study the role of NUAK2 during neural tube morphogenesis, neurospheres and cerebral organoids (or minibrain) were generated from control and patient-derived induced pluripotent stem cells. Mutant neurospheres showed abnormal shape and extreme up-regulation of muscle alpha-actin isoforms compared to control. Abnormal neural tube-like structures were also observed in mutant minibrains, indicating that NUAK2 is key to impart proper neuroepithelial architecture. SILAC pull-down and minibrain immunostainings confirmed that NUAK2 interacts with the actomyosin and tubulin networks, forcing apical constriction of neuroepithelial cells. Our results establish NUAK2 as an indispensable kinase for brain development and may also provide valuable insights into the processes that govern cell shape and migration in NUAK2-associated cancers.
BIO-SKETCH
Carine Bonnard started her career as a Research Engineer in Genset, a leading French Biotechnology company now part of Merck Serono. In 2003, she moved to Singapore to work at the Genome Institute of Singapore where she set up high throughput SNP genotyping platforms for GWA studies in the Human Genetics group. In 2008, she received the Singapore International Graduate Award and obtained 4 years later her PhD in Human Genetics and Developmental Biology from NUS Yong Loo Ling School of Medicine. Since then, she has been a Scientific Project Manager in Reversade’s lab. at the Institute of Medical Biology. Together with Reversade’s team, her main focus is to study human monogenic hereditary diseases with extremely rare and fully penetrant phenotypes. She has overseen whole exome sequencing of more than 600 patients and contributed to the realization of two main programs: BMRC-SPF Genetic Orphan Diseases Adopted: Fostering Innovation Therapy (GODAFIT) and BMRC-IAF Singapore Childhood Undiagnosed Diseases (SUREkids). Disease-causative gene for hundreds of patients were identified, helping clinicians to make the right medical diagnosis. Dr. Bonnard has authored over 25 research papers on CNS disorders, developmental biology and cancer. On her free time, Dr. Bonnard co-founded Asian Gut (www.asiangut.com) in collaboration with Scott Savage and Rob Knight’s lab at the UCSD. The main goal of this citizen science project is to promote microbiome awareness and characterize geographical differences in the human microbiome.
Failure of neural tube closure during embryonic development can result in anencephaly (absence of brain) which is one of the most severe and common birth defects worldwide (5-10 cases in 10,000 live births). To better understand its aetiology and pathogenesis we selected families with recurrent anencephalic foetuses. By whole-exome sequencing, we identified a recessive germline 21 bp in-frame deletion in the NUAK2 gene that segregated with the absence of brain in three foetuses born to consanguineous parents. NUAK2 (a.k.a SNARK) encodes a serine/threonine kinase, a member of the AMPK-related kinase family. In vitro phosphorylation assays demonstrated that the 7 amino-acid deletion in the NUAK2 kinase domain abrogated its kinase activity. Consistent with this being a null allele, a knockout of NUAK2 in mice also caused severe exencephaly (Ohmura et al., 2012). To further study the role of NUAK2 during neural tube morphogenesis, neurospheres and cerebral organoids (or minibrain) were generated from control and patient-derived induced pluripotent stem cells. Mutant neurospheres showed abnormal shape and extreme up-regulation of muscle alpha-actin isoforms compared to control. Abnormal neural tube-like structures were also observed in mutant minibrains, indicating that NUAK2 is key to impart proper neuroepithelial architecture. SILAC pull-down and minibrain immunostainings confirmed that NUAK2 interacts with the actomyosin and tubulin networks, forcing apical constriction of neuroepithelial cells. Our results establish NUAK2 as an indispensable kinase for brain development and may also provide valuable insights into the processes that govern cell shape and migration in NUAK2-associated cancers.
BIO-SKETCH
Carine Bonnard started her career as a Research Engineer in Genset, a leading French Biotechnology company now part of Merck Serono. In 2003, she moved to Singapore to work at the Genome Institute of Singapore where she set up high throughput SNP genotyping platforms for GWA studies in the Human Genetics group. In 2008, she received the Singapore International Graduate Award and obtained 4 years later her PhD in Human Genetics and Developmental Biology from NUS Yong Loo Ling School of Medicine. Since then, she has been a Scientific Project Manager in Reversade’s lab. at the Institute of Medical Biology. Together with Reversade’s team, her main focus is to study human monogenic hereditary diseases with extremely rare and fully penetrant phenotypes. She has overseen whole exome sequencing of more than 600 patients and contributed to the realization of two main programs: BMRC-SPF Genetic Orphan Diseases Adopted: Fostering Innovation Therapy (GODAFIT) and BMRC-IAF Singapore Childhood Undiagnosed Diseases (SUREkids). Disease-causative gene for hundreds of patients were identified, helping clinicians to make the right medical diagnosis. Dr. Bonnard has authored over 25 research papers on CNS disorders, developmental biology and cancer. On her free time, Dr. Bonnard co-founded Asian Gut (www.asiangut.com) in collaboration with Scott Savage and Rob Knight’s lab at the UCSD. The main goal of this citizen science project is to promote microbiome awareness and characterize geographical differences in the human microbiome.

Xiaohong XU
TLGM, A*STAR/NUS
Huntington Disease modeling using isogenic human iPSC
TLGM, A*STAR/NUS
Huntington Disease modeling using isogenic human iPSC
ABSTRACT
Huntington disease (HD) is a dominant neurodegenerative disorder caused by a CAG repeat expansion in HTT. The phosphorylation at serine-421 (pS421) of mutant HTT (mHTT) protein was previously reported to be neuroprotective in HD cellular models in vitro, and rodent models in vivo. However, the genetic context of those cellular and animal models are quite different from that in human HD patients. Here, we employed HD human pluripotent stem cells (hiPSCs) containing endogenous levels of full length mHTT. Using genome editing approaches, we generated isogenic HD hiPSC lines in which the S421 site in mHTT has been mutated into a phosphomimetic aspartic acid (S421D) or phospho-resistant alanine (S421A). We observed that the status of pS421-mHTT affects several aspects of mitochondrial morphology including mitochondrial surface area, volume, surface area to volume ratio, and total numbers, as well as susceptibility to cell death in hiPSC-derived neural cells. We further observed amelioration of transcriptional changes in mitochondrial-related genes in neural cells with S421D but not the S421A form of mHTT. Our results show that post-translational modification at S421 may modulate the toxicity of the full-length mHTT protein at least in part by affecting HD-associated mitochondrial alterations. Our study highlights a facet of the relationship between mHTT and mitochondrial dysfunction in the context of human physiology, with potential relevance to the pathogenesis of HD.
BIO-SKETCH
Xiaohong Xu (MD, PhD) earned her Bachelor’s Degree in Clinical Medicine in 2008, and PhD in Histology and Embryology in 2013, both from Harbin Medical University, China. She was a visiting PhD student in GlaxoSmithKline R&D China from August 2009 to May 2013. In GSK, her research mainly focused on neurodegenerative disease (Alzheimer’s disease and Parkinson’s disease) modeling and drug screening using hESC/hiPSC-derived neuronal cells. In June 2013, she joined Dr. Mahmoud A. Pouladi’s lab in TLGM as a Research Fellow. In TLGM, Xiaohong is leading projects about validation of putative therapeutic targets in neuronal progenitor cells (NPCs) and neurons, which were derived from HD patient hiPSCs and isogenic hiPSC lines generated via TALEN and CRISPR-based genome editing approaches. In general, Xiaohong is interested in neurodegenerative disease modeling, drug screening, and disease therapy based on hiPSCs/hESCs.
Huntington disease (HD) is a dominant neurodegenerative disorder caused by a CAG repeat expansion in HTT. The phosphorylation at serine-421 (pS421) of mutant HTT (mHTT) protein was previously reported to be neuroprotective in HD cellular models in vitro, and rodent models in vivo. However, the genetic context of those cellular and animal models are quite different from that in human HD patients. Here, we employed HD human pluripotent stem cells (hiPSCs) containing endogenous levels of full length mHTT. Using genome editing approaches, we generated isogenic HD hiPSC lines in which the S421 site in mHTT has been mutated into a phosphomimetic aspartic acid (S421D) or phospho-resistant alanine (S421A). We observed that the status of pS421-mHTT affects several aspects of mitochondrial morphology including mitochondrial surface area, volume, surface area to volume ratio, and total numbers, as well as susceptibility to cell death in hiPSC-derived neural cells. We further observed amelioration of transcriptional changes in mitochondrial-related genes in neural cells with S421D but not the S421A form of mHTT. Our results show that post-translational modification at S421 may modulate the toxicity of the full-length mHTT protein at least in part by affecting HD-associated mitochondrial alterations. Our study highlights a facet of the relationship between mHTT and mitochondrial dysfunction in the context of human physiology, with potential relevance to the pathogenesis of HD.
BIO-SKETCH
Xiaohong Xu (MD, PhD) earned her Bachelor’s Degree in Clinical Medicine in 2008, and PhD in Histology and Embryology in 2013, both from Harbin Medical University, China. She was a visiting PhD student in GlaxoSmithKline R&D China from August 2009 to May 2013. In GSK, her research mainly focused on neurodegenerative disease (Alzheimer’s disease and Parkinson’s disease) modeling and drug screening using hESC/hiPSC-derived neuronal cells. In June 2013, she joined Dr. Mahmoud A. Pouladi’s lab in TLGM as a Research Fellow. In TLGM, Xiaohong is leading projects about validation of putative therapeutic targets in neuronal progenitor cells (NPCs) and neurons, which were derived from HD patient hiPSCs and isogenic hiPSC lines generated via TALEN and CRISPR-based genome editing approaches. In general, Xiaohong is interested in neurodegenerative disease modeling, drug screening, and disease therapy based on hiPSCs/hESCs.

Chrishan RAMACHANDRA
National Heart Centre Singapore
iPSC translational medicine: from patient to bench and back
National Heart Centre Singapore
iPSC translational medicine: from patient to bench and back
ABSTRACT
Loss-of-function mutations in the hERG gene causes long-QT syndrome type 2 (LQT2), a condition associated with arrhythmia and sudden cardiac death. Four different mutation classes define the molecular mechanisms impairing hERG. Among them, Class 2 mutations determine hERG trafficking defects. Lumacaftor (LUM) is a drug which acts on channel trafficking, successfully tested for cystic fibrosis and its safety profile is well known. We hypothesize that LUM may also rescue hERG trafficking defects in LQT2 and exert anti-arrhythmic effects. From five LQT2 patients, we generated induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) harboring Class 1 and 2 mutations. LQT2-CMs mimicked the clinical phenotype and showed both prolonged corrected field potential durations (cFPD) and increased arrhythmias evidenced by severe calcium handling irregularities. LUM significantly shortened cFPD in Class 2 LQT2-CMs by correcting the hERG trafficking defect. Furthermore, LUM reduced arrhythmic events by decreasing RyR2S2808 phosphorylation in both Class 1 and 2 LQT2-CMs. Lumacaftor, a drug already in clinical use, can rescue the pathological phenotype of LQT2-CMs, particularly those derived from Class 2 mutated patients. Our results suggest that the use of LUM may represent a novel therapeutic option for LQT2 patients not protected by β-blockers.
BIO-SKETCH
After pursing a Ph.D. at the National University of Singapore, Chrishan Ramachandra joined National Heart Centre Singapore as a Research Fellow where his focus is on understanding human cardiac biology. Using pluripotent stem cells as a developmental model, Chrishan identified key signalling pathways involved in human cardiogenesis. In 2015, he was awarded the Young Investigator’s Award by the Singapore Cardiac Society for his discovery of the ErbB4-p38g signalling cascade and its implication in cardiomyocyte differentiation. Leveraging on his understanding of human cardiomyocyte development, Chrishan has ventured into translational research which includes generation of patient-specific disease models for congenital channelopathies, cardiomyopathies and structural heart defects. Chrishan is the recipient of the SingHealth Foundation Start-Up grant and his recent publication in European Heart Journal regarding the repurposing of existing drugs to treat Long QT syndrome will have meaningful impact on patient health care in the near future.
Loss-of-function mutations in the hERG gene causes long-QT syndrome type 2 (LQT2), a condition associated with arrhythmia and sudden cardiac death. Four different mutation classes define the molecular mechanisms impairing hERG. Among them, Class 2 mutations determine hERG trafficking defects. Lumacaftor (LUM) is a drug which acts on channel trafficking, successfully tested for cystic fibrosis and its safety profile is well known. We hypothesize that LUM may also rescue hERG trafficking defects in LQT2 and exert anti-arrhythmic effects. From five LQT2 patients, we generated induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) harboring Class 1 and 2 mutations. LQT2-CMs mimicked the clinical phenotype and showed both prolonged corrected field potential durations (cFPD) and increased arrhythmias evidenced by severe calcium handling irregularities. LUM significantly shortened cFPD in Class 2 LQT2-CMs by correcting the hERG trafficking defect. Furthermore, LUM reduced arrhythmic events by decreasing RyR2S2808 phosphorylation in both Class 1 and 2 LQT2-CMs. Lumacaftor, a drug already in clinical use, can rescue the pathological phenotype of LQT2-CMs, particularly those derived from Class 2 mutated patients. Our results suggest that the use of LUM may represent a novel therapeutic option for LQT2 patients not protected by β-blockers.
BIO-SKETCH
After pursing a Ph.D. at the National University of Singapore, Chrishan Ramachandra joined National Heart Centre Singapore as a Research Fellow where his focus is on understanding human cardiac biology. Using pluripotent stem cells as a developmental model, Chrishan identified key signalling pathways involved in human cardiogenesis. In 2015, he was awarded the Young Investigator’s Award by the Singapore Cardiac Society for his discovery of the ErbB4-p38g signalling cascade and its implication in cardiomyocyte differentiation. Leveraging on his understanding of human cardiomyocyte development, Chrishan has ventured into translational research which includes generation of patient-specific disease models for congenital channelopathies, cardiomyopathies and structural heart defects. Chrishan is the recipient of the SingHealth Foundation Start-Up grant and his recent publication in European Heart Journal regarding the repurposing of existing drugs to treat Long QT syndrome will have meaningful impact on patient health care in the near future.

Kagistia Hana UTAMI
TLGM, A*STAR/NUS
Modelling Fragile X syndrome using human iPSC
TLGM, A*STAR/NUS
Modelling Fragile X syndrome using human iPSC
ABSTRACT
Fragile X syndrome (FXS) is the most common monogenic form of intellectual disability. FXS is caused by epigenetic silencing of FMR1 and loss of its protein product, FMRP. While many therapeutic strategies have shown promise in animal models of FXS, translation into clinical benefit has remained elusive. Human pluripotent stem cells have emerged in recent years as a way to overcome the challenging inaccessibility of the human brain and to enable the study of the cellular and molecular basis of neurological disorders in the context of human physiology. In this talk, I will discuss our current progress in modelling FXS-related neurodevelopmental deficits using human pluripotent stem cells.
BIO-SKETCH
Kagistia obtained her PhD from the National University of Singapore while carrying out her research in the Genome Institute of Singapore (A*STAR) under the supervision of Dr. Sonia Davila and Dr. Valere Cacheux. During this time, she developed an interest in neurodevelopmental disorders (NDDs), and in particular investigating the functional significance of candidate mutations identified in idiopathic NDDs. In 2014, she joined Dr. Mahmoud Pouladi's lab at TLGM as a Postdoctoral Fellow. The current focus of her research is the development of a human pluripotent stem-cell based model of Fragile X syndrome, the most common inherited form of intellectual disability and a variant of Autism Spectrum Disorders, with the goal of identifying and validating targets of therapeutic potential.
Fragile X syndrome (FXS) is the most common monogenic form of intellectual disability. FXS is caused by epigenetic silencing of FMR1 and loss of its protein product, FMRP. While many therapeutic strategies have shown promise in animal models of FXS, translation into clinical benefit has remained elusive. Human pluripotent stem cells have emerged in recent years as a way to overcome the challenging inaccessibility of the human brain and to enable the study of the cellular and molecular basis of neurological disorders in the context of human physiology. In this talk, I will discuss our current progress in modelling FXS-related neurodevelopmental deficits using human pluripotent stem cells.
BIO-SKETCH
Kagistia obtained her PhD from the National University of Singapore while carrying out her research in the Genome Institute of Singapore (A*STAR) under the supervision of Dr. Sonia Davila and Dr. Valere Cacheux. During this time, she developed an interest in neurodevelopmental disorders (NDDs), and in particular investigating the functional significance of candidate mutations identified in idiopathic NDDs. In 2014, she joined Dr. Mahmoud Pouladi's lab at TLGM as a Postdoctoral Fellow. The current focus of her research is the development of a human pluripotent stem-cell based model of Fragile X syndrome, the most common inherited form of intellectual disability and a variant of Autism Spectrum Disorders, with the goal of identifying and validating targets of therapeutic potential.

Shi Yan NG
IMCB, A*STAR
Using patient-derived induced pluripotent stem cells to understand metabolic defects in
neurodegeneration
IMCB, A*STAR
Using patient-derived induced pluripotent stem cells to understand metabolic defects in
neurodegeneration
ABSTRACT
Age-onset neurodegeneration is one of the top causes of death globally in 2015 (World Health Organization). Using an established stem cell-based system to model Amyotrophic Lateral Sclerosis, we found that metabolic dysfunctions in the diseased motor neurons can be attributed to post-translational modifications of a mitochondria protein. We show that reversing this pathogenic modification by a small molecule promotes motor neuron survival.
BIO-SKETCH
Dr. Shi-Yan Ng is a junior Principal Investigator at the Institute of Molecular and Cell Biology (IMCB) and adjunct Assistant Professor at National University of Singapore (Yong Loo Lin School of Medicine) since October 2015. Her research work centers around using patient-derived induced pluripotent stem cells (iPSCs) and more recently neural organoid technologies to unravel early events in human neurodegeneration that can be therapeutically targeted. Dr. Ng has more than 10 years of experience with human pluripotent stem cells and neuronal differentiation, and has published a number of high impact studies that are highly cited. For her research, Dr. Ng has won the Merck Millipore Young Scientist Award (Third Prize) in 2011 and the A*STAR International Fellowship in 2012. During her postdoctoral training in Professor Lee Rubin¹s lab at Harvard University, she was also involved in several collaborations with biotech companies including Vertex Pharmaceuticals, Evotec A.G and Syros Pharmaceuticals. As such, she aims to close the translational gap through her research using patient-derived stem cells.
Age-onset neurodegeneration is one of the top causes of death globally in 2015 (World Health Organization). Using an established stem cell-based system to model Amyotrophic Lateral Sclerosis, we found that metabolic dysfunctions in the diseased motor neurons can be attributed to post-translational modifications of a mitochondria protein. We show that reversing this pathogenic modification by a small molecule promotes motor neuron survival.
BIO-SKETCH
Dr. Shi-Yan Ng is a junior Principal Investigator at the Institute of Molecular and Cell Biology (IMCB) and adjunct Assistant Professor at National University of Singapore (Yong Loo Lin School of Medicine) since October 2015. Her research work centers around using patient-derived induced pluripotent stem cells (iPSCs) and more recently neural organoid technologies to unravel early events in human neurodegeneration that can be therapeutically targeted. Dr. Ng has more than 10 years of experience with human pluripotent stem cells and neuronal differentiation, and has published a number of high impact studies that are highly cited. For her research, Dr. Ng has won the Merck Millipore Young Scientist Award (Third Prize) in 2011 and the A*STAR International Fellowship in 2012. During her postdoctoral training in Professor Lee Rubin¹s lab at Harvard University, she was also involved in several collaborations with biotech companies including Vertex Pharmaceuticals, Evotec A.G and Syros Pharmaceuticals. As such, she aims to close the translational gap through her research using patient-derived stem cells.

Voja JOVANOVIC
Stem Cell Technologies, Account Manager
Stem Cell Technologies, Account Manager
BIO-SKETCH
Voja is a scientist by training interested in innovation commercialization and bio-pharmaceutical industry. He is currently working as an Account manager for the Canadian biotech company STEMCELL Technologies. His main responsibilities are to provide technical advice and to support scientists working on cellular therapy research and disease modeling with stem cells. Apart from scientific communication, Voja also specializes in regulatory affairs matters and quality systems. As a scientist, Voja has worked in France and Singapore. His research work covered biomarker discovery in organ transplantation and autoimmune diseases, antibody development and emerging diseases. In his 10 years of research career, Voja co-authored 13 peer-reviewed publications. In order to gain vital skills and knowledge that were essential for his career transition to commercial roles in the biotech industry, Voja completed a part-time MBA.
Voja is a scientist by training interested in innovation commercialization and bio-pharmaceutical industry. He is currently working as an Account manager for the Canadian biotech company STEMCELL Technologies. His main responsibilities are to provide technical advice and to support scientists working on cellular therapy research and disease modeling with stem cells. Apart from scientific communication, Voja also specializes in regulatory affairs matters and quality systems. As a scientist, Voja has worked in France and Singapore. His research work covered biomarker discovery in organ transplantation and autoimmune diseases, antibody development and emerging diseases. In his 10 years of research career, Voja co-authored 13 peer-reviewed publications. In order to gain vital skills and knowledge that were essential for his career transition to commercial roles in the biotech industry, Voja completed a part-time MBA.

Yann Chong TAN
Atreca, Head of Research
Atreca, Head of Research
BIO-SKETCH
Tan Yann Chong, PhD, is a co-founder of Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response. Dr. Tan invented Atreca’s Immune Repertoire CaptureTM technology while pursuing his dissertation research in William Robinson’s laboratory at Stanford University. At Atreca, he industrialized the technology and made significant technological improvements. Immune Repertoire CaptureTM is validated by multiple partnerships with major pharmaceutical companies, academic partners and non-profit organizations. Dr. Tan is currently the Head of Research at Atreca’s Singapore site and is responsible for research and development activities in Singapore. Dr. Tan is a recipient of the prestigious A*STAR NSS scholarship and received a BS in Biology from Duke University and a PhD in Immunology from Stanford University.
Tan Yann Chong, PhD, is a co-founder of Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response. Dr. Tan invented Atreca’s Immune Repertoire CaptureTM technology while pursuing his dissertation research in William Robinson’s laboratory at Stanford University. At Atreca, he industrialized the technology and made significant technological improvements. Immune Repertoire CaptureTM is validated by multiple partnerships with major pharmaceutical companies, academic partners and non-profit organizations. Dr. Tan is currently the Head of Research at Atreca’s Singapore site and is responsible for research and development activities in Singapore. Dr. Tan is a recipient of the prestigious A*STAR NSS scholarship and received a BS in Biology from Duke University and a PhD in Immunology from Stanford University.

Sandhya SRIRAM
Scientist-entrepreneur-blogger
Scientist-entrepreneur-blogger
BIO-SKETCH
Sandhya is an entrepreneurial scientist and blogger currently working as a Programme Management Officer at Singapore Bioimaging Consortium (SBIC), A*STAR. She recently transitioned into a management role from research - prior to this, she was a Research Fellow in the same institute working on adipose and dental stem cells, pluripotency, oxidative stress and obesity. Sandhya is also the founder and CEO of her latest venture, SciGlo, which caters to helping people in STEM. It is a web resource hub and solution platform to build a community of students, researchers and scientists from various science sectors. She has been featured in Forbes - Women@Forbes for her entrepreneurial work. She strongly believes that innovation and entrepreneurship in the health sciences, biotech and healthcare sectors is the way to go and the only way mankind can exist in the future. Her passion has always been to do meaningful science and not fall into the trap of "publish or perish"! Starting up her own company/website(s) SciGlo and Biotechin.Asia, has been an eye opening experience, through which she further discovered her passion for the "right" science. She is a science enthusiast and wears many hats, along with being a mother of a very active and inquisitive son. Sandhya holds a PhD in Biological Sciences and gives back to the student population by conducting/speaking at various workshops for careers in biotech and biomedical sciences, science communication and women in science. She is also a startup mentor at Vertical VC, Finland. She is a strong supporter of women in science and is passionate about this topic. Sandhya has also recently ventured into travel/lifestyle/fashion blogging.
Sandhya is an entrepreneurial scientist and blogger currently working as a Programme Management Officer at Singapore Bioimaging Consortium (SBIC), A*STAR. She recently transitioned into a management role from research - prior to this, she was a Research Fellow in the same institute working on adipose and dental stem cells, pluripotency, oxidative stress and obesity. Sandhya is also the founder and CEO of her latest venture, SciGlo, which caters to helping people in STEM. It is a web resource hub and solution platform to build a community of students, researchers and scientists from various science sectors. She has been featured in Forbes - Women@Forbes for her entrepreneurial work. She strongly believes that innovation and entrepreneurship in the health sciences, biotech and healthcare sectors is the way to go and the only way mankind can exist in the future. Her passion has always been to do meaningful science and not fall into the trap of "publish or perish"! Starting up her own company/website(s) SciGlo and Biotechin.Asia, has been an eye opening experience, through which she further discovered her passion for the "right" science. She is a science enthusiast and wears many hats, along with being a mother of a very active and inquisitive son. Sandhya holds a PhD in Biological Sciences and gives back to the student population by conducting/speaking at various workshops for careers in biotech and biomedical sciences, science communication and women in science. She is also a startup mentor at Vertical VC, Finland. She is a strong supporter of women in science and is passionate about this topic. Sandhya has also recently ventured into travel/lifestyle/fashion blogging.

Michael TILLMANN
CEO, Vela Diagnostics
CEO, Vela Diagnostics
BIO-SKETCH
Michael Tillmann has 25 years of experience in senior executive positions for multinational companies in the pharmaceutical and diagnostics industry. As CEO, Mr Tillmann founded Vela Diagnostics with the vision of establishing the company as a global provider of integrated IVD solutions that address individual customer needs in molecular diagnostics. Previously he was President & CEO for Roche Diagnostics in North America and before that in Asia Pacific and Europe. Prior to the Roche assignments, Mr Tillmann was Managing Director of the start-up company artus GmbH, which was later acquired by Qiagen. Mr Tillmann started his career in a pharmaceutical trading house, Holstein GmbH, as Managing Director, representing over 20 principals in Japan and South East Asia.
Michael Tillmann has 25 years of experience in senior executive positions for multinational companies in the pharmaceutical and diagnostics industry. As CEO, Mr Tillmann founded Vela Diagnostics with the vision of establishing the company as a global provider of integrated IVD solutions that address individual customer needs in molecular diagnostics. Previously he was President & CEO for Roche Diagnostics in North America and before that in Asia Pacific and Europe. Prior to the Roche assignments, Mr Tillmann was Managing Director of the start-up company artus GmbH, which was later acquired by Qiagen. Mr Tillmann started his career in a pharmaceutical trading house, Holstein GmbH, as Managing Director, representing over 20 principals in Japan and South East Asia.

Claire Ann CANNING
LKC School of Medicine
LKC School of Medicine
BIO-SKETCH
Claire Ann Canning graduated from the National University of Ireland with a BSc. (Hons) degree in Biochemistry in 1998. After gaining a MSc. in Medical Genetics and Immunology, she was awarded her PhD in 2002 in the field of Sex Determination (Developmental Genetics) from the National Institute of Medical Research, UK. Claire relocated to Singapore in 2004, where until 2012, she was a senior research fellow at A*STAR. Her research interests were primarily in the field of embryology studying signalling pathways and their involvement in normal development and disease. In January 2013, Claire joined LKC School of Medicine and is the Lead for Introduction to Medical Sciences, the Lead for Laboratory Practical’s, and a Team Based Learning Facilitator. Claire is also a Tutor in the Alexander Fleming House.
Claire Ann Canning graduated from the National University of Ireland with a BSc. (Hons) degree in Biochemistry in 1998. After gaining a MSc. in Medical Genetics and Immunology, she was awarded her PhD in 2002 in the field of Sex Determination (Developmental Genetics) from the National Institute of Medical Research, UK. Claire relocated to Singapore in 2004, where until 2012, she was a senior research fellow at A*STAR. Her research interests were primarily in the field of embryology studying signalling pathways and their involvement in normal development and disease. In January 2013, Claire joined LKC School of Medicine and is the Lead for Introduction to Medical Sciences, the Lead for Laboratory Practical’s, and a Team Based Learning Facilitator. Claire is also a Tutor in the Alexander Fleming House.

Siew Hwa ONG
Acumen Research Laboratories, Director and Chief Scientist
Acumen Research Laboratories, Director and Chief Scientist
BIO-SKETCH
Siew Hwa ONG is an accomplished scientist with deep experience in multiple advanced fields, including cell and molecular biology, genetics, genomics, as well as diagnostics and drug product development. She has naturally transitioned into a career in the industry, including both large, global pharmaceutical company and founding a molecular diagnostic company. Working in the academia and industry for over 20 years in Singapore US and Canada, Dr. Ong has an impressive track record of translation of basic research into innovative biomedical products and technology commercialization, including licensing of intellectual property and strategic partnerships. Founded in 2010, Acumen Research Laboratories (ARL) is a medical technology firm with core competency is biomarker discovery and development of molecular diagnostic tests, it has successfully pioneered a break-through, host response Sepsis test. Dr. Ong has been an adjunct faculty member at the National University of Singapore, Yong Loo Lin School of Medicine since 2004. She is also serving as the Chairman of BioSingapore and a council member of the Singapore Manufacturing Federation, as well as serving in the Biomedical and Health Standards Committee under the Singapore Standards Council (SPRING Singapore). Dr. Ong has also set up non-profit programs such as the Science Explorers’ Camp and Asian Youth Biotechnology Network. She also strongly believes in building high-tech human capital and has been a speaker at multiple career talks for youths to introduce to them careers in innovation-driven industries based on science and technology.
Siew Hwa ONG is an accomplished scientist with deep experience in multiple advanced fields, including cell and molecular biology, genetics, genomics, as well as diagnostics and drug product development. She has naturally transitioned into a career in the industry, including both large, global pharmaceutical company and founding a molecular diagnostic company. Working in the academia and industry for over 20 years in Singapore US and Canada, Dr. Ong has an impressive track record of translation of basic research into innovative biomedical products and technology commercialization, including licensing of intellectual property and strategic partnerships. Founded in 2010, Acumen Research Laboratories (ARL) is a medical technology firm with core competency is biomarker discovery and development of molecular diagnostic tests, it has successfully pioneered a break-through, host response Sepsis test. Dr. Ong has been an adjunct faculty member at the National University of Singapore, Yong Loo Lin School of Medicine since 2004. She is also serving as the Chairman of BioSingapore and a council member of the Singapore Manufacturing Federation, as well as serving in the Biomedical and Health Standards Committee under the Singapore Standards Council (SPRING Singapore). Dr. Ong has also set up non-profit programs such as the Science Explorers’ Camp and Asian Youth Biotechnology Network. She also strongly believes in building high-tech human capital and has been a speaker at multiple career talks for youths to introduce to them careers in innovation-driven industries based on science and technology.
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