Join us October 12-16, 2020 to hear from this phenomenal speaker lineup!
This year’s event features over 30 presentations from thought leaders and prominent researchers around the world. Join them as they share developments, discoveries, and cutting-edge content connected to a variety of stem cell applications, including disease and cell modeling, cell and gene therapy, and much more.
A live keynote presentation will be given each day of the event at the times noted below. All presentations will be recorded and made available for your convenience.
Monday, October 12 @ 10:00AM Taipei Standard Time / 7:00PM PDT (prior day)
Associate Research Fellow, Genomics Research Center, Academia Sinica, Taipei, Taiwan
2000—PhD Institute of Microbiology, National Taiwan University
1994—MS Institute of Molecular Medicine, National Taiwan University
1992—BS Department of Medical Technology, National Taiwan University
2018-present Adjunct Associate Professor, Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
2016-present Adjunct Associate Professor, Department of Life Science, Tzu Chi University, Taiwan
2015-present Associate Research Fellow, Stem Cell Program, Genomics Research Center, Academia Sinica, Taiwan
2015-present Adjunct Associate Professor, Genomics and System Biology Program, College of Life Science, National Taiwan University, Taiwan
2003-2007 Postdoctoral Fellow/Associate, Molecular, Department of Cellular, and Developmental Biology, Yale University, USA
Presentation: A high-throughput functional screen reveals human embryonic stem cell self-renewal signals
Tuesday, October 13 @ 12:00PM AEST / 7:00PM PDT
Research Fellow, St. Vincent’s Institute, Melbourne, Australia
Presentation: Heart disease in a dish: human iPSC-derived multicellular cardiac organoids
Wednesday, October 14 @ 1:00PM PDT
Director, Division of Stem Cell Biology Research, Beckman Research Institute of City of Hope, California, USA
Presentation: Human iPSC-Based Disease Modeling and Therapeutic Development
Thursday, October 15 @ 1:00PM EDT / 10:00AM PDT
Canada Research Chair in Synthetic Neuroimmunology and Stem Cell Bioengineering, University of Toronto, Canada
Presentation: Personalized immuno-neuroscience and glio-immunology: towards human culture models of innate responses in the brain
The brain harbors a resident innate immune system, finding its origins early in development. These immune cells, the microglia, along with rare patrolling peripheral blood cells, contribute to the development, maturation, homeostasis, and perhaps eventual demise of the nervous system. We use humanized in vitro models to investigate the role of these cells in health and disease. Mutations and polymorphisms affecting genes expressed solely in microglia are associated with conditions ranging from psychiatric disorders of developmental origin (e.g. Schizophrenia), to age-related neurological disorders (e.g. Alzheimer’s). Using primary benchmarks and single cell profiling, combined with tissue engineering, we aim to better replicate cellular identity in our cultures, as a prerequisite for identification of disease-associated phenotypes. Functional variations affecting microglial homeostatic behavior and reactivity, at different stages of development and different ages, eventually lead to neuronal dysfunction, loss of connectivity, or death. We use the CRISPR/Cas9 toolkit to engineer putative disease-associated variants in pluripotent stem cells. Glial cells such as microglia and astrocytes are capable of sensing and reacting to various stimuli, such as immune/inflammatory modulators. As such, they are uniquely suited to integrate peripheral inputs (pathogens, microbiota, cytokines), as well CNS-centric stimuli (synaptic plasticity, electrophysiological activity, metabolic demands, cell death) over time, ultimately affecting the health of our neural networks, for better or worse. While their roles in development are under evolutionary constraint, their actions in disease or during aging can be maladaptive. Our ultimate goal is to identify and control inflammatory processes that precede, sometimes by decades, the largely irreversible neuronal dysfunction seen in patients with neurological and psychiatric disorders.
Friday, October 16 @ 9:00AM CEST / 12:00AM PDT
Scientist and Principal Investigator at the Institute of Human Genetics, University Hospital Essen, Germany
Dr. Laura Steenpass received her PhD at the Children’s Cancer Research Institute (CCRI) in 2002 where her research focus was protein-protein interactions and Ewing’s sarcoma. She was later a PostDoc in the lab of Prof. Denise Barlow at the Center for Molecular Medicine (CeMM) in Vienna, Austria until 2006. Her research focus was genomic imprinting at the murine lgf2r/Airn locus. Dr. Steenpass also served as a PostDoc at the Department of Pediatric Oncology, Hematology and Immunology, University Hospital Düsseldorf, Germany from 2006 to 2009. She now serves as a scientist and PI at the Institute of Human Genetics, University Hospital Essen, Germany with a research focus of modeling of imprinting diseases and retinoblastoma with human pluripotent stem cells. Most recently, Dr. Steenpass is Head of Department Human and Animal Cell Cultures at the Leibniz-Institute DSMZ – German Collection of Microorganisms and Cell Cultures and Professor for Cell Biology at the Technical University Braunschweig, Germany.
Presentation: A human stem cell–based model for retinoblastoma
Retinoblastoma is the most common eye cancer occurring in children under the age of five. It is caused by biallelic inactivation of the retinoblastoma gene RB1, presumably in cone precursor cells of the human retina. Efforts to model retinoblastoma in mouse are not satisfactory as the mutation of Rb1 alone is not sufficient for tumor formation. In order to analyze especially early stages of retinoblastoma we have created a human organoid-based model using the CRISPR/Cas9 system. The human embryonic stem cell (hESC) line H9 was modified to generate sublines carrying a random mutation in exon 3 (close to the splice donor site) or a deletion of RB1 exon1 including the promoter. Both modifications were established either on one or both RB1 alleles. All cell lines have been characterized thoroughly and tested for pluripotency. Comparative differentiation into retinal organoids using the parental cell line H9, a heterozygous and a homozygous subline of each modification was performed. As analyzed by immunocytochemistry, generated retinal organoids contain all seven retinal cell types – the mature rod (NRL) and cone (ARR3) photoreceptors are present in the outer layer and ganglion cells (POU4F1), Müller glia cells (VIM), amacrine cells (TFAP2A), bipolar cells (PRKCA) and horizontal cells (PROX1) are located in the inner layer. Over time, the neural retina layer of the RB1 homozygous organoids became loose and disorganized compared to RB1 wildtype and RB1 heterozygous organoids. Immunostainings on day 152 indicated enhanced proliferation (Ki67), a decrease in rod photoreceptors and an absence of amacrine cells in RB1-/- organoids. Co-staining for Ki67 and ARR3 and subsequent quantification of cell numbers in microscopy images revealed a significant increase of proliferating ARR3+ cone photoreceptors in RB1-/- organoids. Analysis of mRNA expression of marker genes by qRT-PCR on day 126 supported theRB1-/- specific changes in proliferating and amacrine cells and rod photoreceptors. Based on these data, we are convinced that retinal organoids are a suitable model to enhance studies on development of retinoblastoma.
The following presentations will be available on-demand throughout the event - allowing you to watch them at your convenience and at your own pace.
Scientist III, Thermo Fisher Scientific
Presentation: Addressing the Needs of 3D Suspension Culture Systems Through the Optimization of a New PSC Medium
As the use of pluripotent stem cells (PSCs) in therapeutic and screening applications continues to expand, a key bottleneck is the efficient generation of high-quality PSCs. PSC suspension culture offers key advantages for scale up over adherent culture systems: overall cost; reduced footprint and hands on time; and compatibility with closed systems. In addition, expansion of PSCs in suspension culture consumes less media (and plasticware) than the same number of cells grown in adherent systems. Together, these features makesuspension culture an attractive path for cost-effective and rapid generation of large quantities of cells required for downstream applications.
Although suspension culture offers significant benefits, wider adoption has been limited due to a number of barriers.In particular, there is a lack of effective culture systems and protocols which support PSC suspension culture and scale up. To help address this gap, we have recently developed a new suspension culture media system – Gibco™StemScale™PSC Suspension Medium, which promotes the efficient self-aggregation of singularized PSCs into spheroids, without the need for microcarriers.Spheroids grown in this media maintain robust cell expansion (≥ 8 fold). In addition, the viability and pluripotencyremain high (≥ 90% of cells) for spheroids cultured over consecutive passages. We also demonstrate our new system is compatible with a variety of culture vessels (from well plates to bioreactors) through the optimization of straightforward parameters. We have found PSCs can be maintained in small volume suspension cultures or readily scaled up into large volume culture vessels.
The StemScale PSC Suspension Medium maintenance, feeding and passaging protocols are designed to be simple processes that minimize the risks of cell loss and contamination and that are also scalable and amendable to automation. During routine culture,singularized cells can be replated into adherent cultures, cryopreserved, and/or reseeded back into suspension conditions for continued expansion.
Silvia E. Castro Piedra
Johan E. Morales Sanchez
|Lecturer and Researcher, Biotechnology Research Center, Costa Rica Institute of Technology, Costa Rica||Lecture and Researcher, Biotechnology Research Center, Costa Rica Institute of Technology, Costa Rica|
After graduating with a bachelor’sdegree in Biotechnological Engineering and a master’s degree in Microbiology from the University of Costa Rica in 2019, Silvia Castro has over ten years of experience in Tissue Engineering and Regenerative Medicine research. Also during the same time has been a lecturer of embryology, Human Physiology, Biology and Anatomy, as well cell culture techniques in different Universities in Costa Rica. She has experience using laboratory animals.
She also has participated in different international events as TERMIS as a speaker and several poster presentations and owns publications.
Because of her personal and particular interest she has participated in different congress organization related to health research and worked with different interdisciplinary groups in more than ten projects.
Johan Morales-Sánchez is a biotechnology engineer graduated in 2014 from the Costa Rica Institute of Tecnology (TEC), who currently works as a researcher in the Biotechnology Research Center from TEC. During the last years, he has taught pre-grad students in this university about Biology and Cell Culture, and has also been focused in tissue engineering and laboratory animal research.
Presentation: Stem cell therapies for skin regeneration in animal models, Costa Rica experiences
President & CEO, Hope Biosciences, Texas, USA
Presentation: Optimization and Standardization in Stem Cell Manufacturing for the Fight Against COVID-19
Thomas M. Durcan
Assistant Professor, Montreal Neurological Institute, McGill University, Canada
As an assistant professor at the Montreal Neurological Institute (The Neuro) and McGill University, my research focus is on applying patient-derived stem cells towards the development of phenotypic discovery assays and 3D neuronal organoid models for both neurodegenerative and neurodevelopmental disorders. As associate director of the Early Drug Discovery Unit (EDDU) at The Neuro, I oversee a team of 40+ research staff and students, committed to applying novel stem cell technology, combined with CRISPR genome editing, organoid models and new microfluidic technologies towards elucidating the underlying causes of these complex disorders. Combined with new approaches in the group towards building multiomic profiles and predictive computational models with patient-derived IPSC cells, the long-term strategy over the next decade is to identify new personalized precision therapies that can be applied towards building clinical trials on a dish. Further information on the EDDU can be found on our website https://www.mcgill.ca/neuro/open-science/open-science-platforms/eddu.
Presentation: Modelling disorders of the brain through patient-derived stem cells
My research focus is on applying patient-derived stem cells towards the development of phenotypic discovery assays and 3D mini-brain models for both neurodegenerative and neurodevelopmental disorders. As associate director of the Early Drug Discovery Unit (EDDU) at the Montreal Neurological Institute (MNI), I oversee a team of over 35 research staff and students, committed to applying novel stem cell technology, combined with CRISPR genome editing, mini-brain models and new microfluidic technologies towards elucidating the underlying causes of these complex disorders. Combined with new approaches in the group towards building MultiOmics profiles on the patient-derived IPSC cells, the long-term strategy is to identify new personalized precision therapies that can be applied towards building clinical trials on a dish. For my talk, I will discuss our 3D drug discovery pipeline, in which we focus on translating findings from 2D neurons, into 3D brain organoids, and ultimately into lead compounds. I will present work on how we generate these cells, the quality control process, and also some of the new technologies we are developing in the group for working with 3D neuronal organoids.
Scientist III, Field Applications, Stem Cells and Neurobiology, Thermo Fisher Scientific
Dr. Farah received his doctorate from McGill University in Canada where he studied early embryo lineage specification and development of the female reproductive tract needed for proper embryo-uterine crosstalk. Omar continued his postdoctoral work at the University of California, San Diego where he focused on using stem cell-based models to study extra-embryonic lineage specification, trophoblast differentiation, and placental development.
Presentation: Optimizing stem cell workflows to build better disease models
At Thermo Fisher Scientific, our goal is to bring innovative new products and services that enable the development of more physiological relevant disease models to help accelerate the drug discovery process. In this seminar, we will share an overview of our pluripotent stem cell-based workflow offerings and capabilities used to develop more predictive models. This seminar will review a 5-step guide, from reprogramming, genome engineering, characterization to differentiation, and even downstream analysis assays, needed for the generation of a successful stem cell-based disease model. In addition, specific examples will be provided of how stem cell researchers are leveraging various products and services to build relevant disease models to achieve their research goals.
Postdoctoral Fellow, Human Genome and Stem Cell Research Center, University of Sao Paulo, Brazil
Presentation: Using iPS-derived cells to generate a functional human liver through 3D bioprinting
Associate Professor, Principal Research Fellow, QUT Tier 1 Centre for Genomics and Personalised Health at IHBI, Queensland University of Technology, Australia
Presentation: In vitro models of human neurogenesis
Larisa M Haupt, Rachel K. Okolicsanyi, Chieh Yu, Lotta E. Oikari, Ian W Peall, Lyn R. Griffiths
Assessing the functionality of neuronal cell types is critical to their efficacy in future applications. Understanding how these processes are regulated will help to further unravel the structural complexity of the human brain, and the role of associated biological and other factors in neurogenesis. This information will also have important ramifications for the development of 2D and 3D models to translate cells toward their successful integration of newly formed neurons into existing/remaining neural circuits. The complexity of the neural niche and the ubiquitous presence of the protetoglycan proteins in the neural microenvironment suggest that this will be achievable not by one assay but will more likely be achieved through a combination of data and approaches to identify specific markers and regulatory pathways. Our approach uses human stem cell models and cell lines including human mesenchymal stem cells (hMSC), embryonic derived human neural stem cells (hNSC H9) and ENStem-A neural progenitor cells, as well as the immortalised human neural progenitors (ReNcell CX cell line), in 2D and developing 3D cultures to examine the role of proteoglycans and their use as markers of lineage potential and specification.
Professor and Director, Molecular Neurobiology Laboratory, McLean Hospital/Harvard Medical School, Massachusetts, United States
Presentation: Personalized cell therapy for Parkinson’s disease
Research Assistant Professor, Weill Cornell Medicine, New York, USA
Ritu Kumar is an Assistant Professor of Cell and Developmental Biology Research in Surgery at Weill Cornell Medicine, New York, with a strong background in stem cell research.During her Ph.D. She studied the risk factors associated with calcium oxalate urolithiasis. After finishing her Ph.D. in 2005, Ritu joined Mount Sinai School of Medicine (now the Icahn School of Medicine at Mount Sinai),New York as a post-doc. During her post-doc, Rituinvestigated molecular mechanisms controlling self-renewal and aging of hematopoietic stem cell compartment. Dr. Kumarjoined Weill Cornell Medicine in the year 2009 and her research over the past several years has been focused on understanding the epigenetic basis of somatic cell reprogramming towards induced pluripotent stem cells (iPSC). Ritudiscovered, an epigenetic modifier Activation-Induced Cytidine Deaminase (AICDA) is required for the stabilization of mouse iPSCs during reprogramming and even when iPSCs can be stabilized by modifying the levels of transgenes, they fail to achieve naive pluripotent state and are primed for differentiation, hypermethylated and display hyperactive FGF/ERK signaling. Aftergaining extensive knowledge on the epigenetic basis of mouse pluripotency, Dr. Kumar has shifted her focus to human pluripotent stem cells and her current research is aimed at to decipher the epigenetic basis of human naïve pluripotency, with the eventual goal to establish a stable population of bona-fide human naive pluripotent stem cells in-vitro, which will eventually benefit variousclinical applications of pluripotent stem cells. Additionally, at the Department of Surgery Dr. Kumar is carrying out multiple projects in,related to patient derived iPSCs for disease modeling and cell replacement therapies purposes, including cardiomyopathies and pancreatic disorders. She is working on a number of collaborative projects with various leading stem cell scientist at WCM and also with researchers at neighboring institutes such as the Memorial Sloan Kettering Cancer Center and Rockefeller University.
Presentation: Epigenetic regulation of human naïve pluripotency
Naïve pluripotenct stem cells (PSCs) are the most potent stem cells, with the highest capacity to differentiate into all the cells of the three germ layers without lineage biases, thus hold the greatest promise for the field of regenerative medicine and human disease modeling. Stem cells in pre-implantation epiblast constitutes the naive state, possess unrestricted developmental potency and flexibility to produce all lineages. Conversely, PSCs present in the post implantation blastocyst, designated as epiblast stem cells (EpiSCs) are less plastic and have acquired the genetic and epigenetic landscape for differentiation. That’s why embryonic stem cells (ESCs) are derived from the pre-implantation stage. Contrary to mouse ESCs (mESCs), which are similar to naïve cells, human embryonic stem cells (hESCs) despite their derivation form pre-implantation epiblast are analogous to a late stage EpiSCs and are in primed state. This is a significant drawback for the translational applications of stem cells as primed cells are not at the ground state, are transcriptionally and epigenetically very heterogeneous, contributing to inefficient differentiation and significant variation and non-reproducibility within one and among various cell lines. Epigenetic rewiring is essential for the establishment of naïve pluripotent state. Here I report Activation-Induced Cytidine Deaminase (AICDA) an enzyme involved in DNA-dementylation is a novel regulator of both mouse and human naïve pluripotency. Aicdaknockout mPSCs fail to achieve the naïve pluripotent state, and remain primed for differentiation, because of a failure to suppress FGF/ERK signaling. While the mutant cells display marked genomic hypermethylation, suppression of FGF/ERK signaling by AID is independent of deaminase activity. Similarly, AICDA-mutant hESCs also fail to achieve the naïve state and display hyperactive FGF/ERK signaling. Thus, our study identifies AICDA as a novel regulator of naïve pluripotency through its activity on FGF/ERK signaling and DNA-demethylation, which, in future, will help develop strategies to direct human ESCs to a bona-fide naïve state with high efficiency.
Director, R&D and Lead of Cell Models, Cell Biology, Thermo Fisher Scientific
Presentation: Differentiation of iPSCs in 3D: Leveraging Suspension Cultures for Scale and Efficiency
Assistant Professor, Washington University School of Medicine, St. Louis, USA
Presentation: Insulin-producing islets to combat diabetes from stem cells
Post Doctoral Research Fellow, Institute for Bioengineering and Biosciences (iBB), University of Lisbon, Portugal
Cláudia Miranda is currently a Post Doctoral Research Fellow at iBB – Institute for Bioengineering and Biosciences/Instituto Superior Técnico. The main focus of her research is the development of a scalable and cost-effective culture platforms for expansion of human pluripotent stem cells and their controlled differentiation into different lineages for drug discovery and toxicity assessment.After finishing a Degree in Biochemistry, she received a MSc. in Biotechnology and a Ph.D. in Biotechnology and Biosciences at Instituto Superior Técnico, University of Lisbon, focusing on the 3D culture and neural induction of human pluripotent stem cells.
Presentation: Development of a robust and scalable culture platform for expansion and neural induction of human pluripotent stem cells in suspension culture
The demand for large cell numbers for applications in cellular therapies and drug screening requires the development of scalable platforms capable of generating high quality populations of tissue-specific cells derived from human pluripotent stem cells (hPSCs). This work describes the scaling-up of an aggregate-based suspension culture system for expansion and neural induction of human pluripotent stem cells using a novel medium formulation: Gibco StemScale PSC Suspension Medium.
Here, we studied the ability of StemScale Medium to promote the rapid expansion of hPSC cultures as spheroids grown in suspension. We tested human induced pluripotent stem cell (hiPSC) growth in 6-well plates (on orbital shaker platforms) and spinner flasks for a total of 3 consecutive passages. Up to a 9-fold increase in cell number was observed over 5 days per passage, with a cumulative fold change up to 600 in 15 days. This expansion would enable literscale bioreactors to be seeded if starting from a 6-well plate suspension culture. Using this process, we were also able to maintain high levels of pluripotency markers (≥95% OCT4) at the end of the expansion, all whilst maintaining a normal karyotype. Additionally, we compared neural induction of hiPSCs by using a dual SMAD inhibition protocol with a commercially available neural induction medium. Since initial aggregate size has an important impact in the commitment of hiPSC into a particular lineage, a previously determined combination of seeding density and agitation rate was successfully used to produce homogeneous populations of hiPSC aggregates with an optimal and narrow distribution of diameters. With StemScale Medium, we were able to obtain up to a 32-fold increase in cell number at the end of a 7-day neural induction protocol within an 80 mL spinner flask. The hiPSC-derived neural progenitors underwent further maturation that stained positive for Tuj1 and were responsive to KCl and Histamine treatments.
The results presented in this work should set the stage for the future generation of a clinically relevant number of human neural progenitors for transplantation and other biomedical applications using controlled, automated and reproducible large-scale bioreactor culture systems.
Laila M. Montaser
Professor in Clinical Pathology and Hematology, Menoufia University, Egypt
Presentation: Using Stem Cells in Cartilage Repair and Tissue Engineering
|Scientist, Biogen, Cambridge, USA||Staff Scientist, Biogen, Cambridge, USA|
Naomi Okugawa PhD is a Scientist at Biogen, Cambridge, MA. She obtained her PhD in Japan, then performed postdoctoral training at Massachusetts General Hospital and Novartis. She worked and learned human iPSC at Harvard Stem Cell Institute. Her focus is establishing better iPSC models to understand neurological disorders for drug discovery, and her group has been supporting various disease research groups at Biogen by providing iPSC-derived neurons and glial cells.
Dirk Walther obtained his PhD in the group of Matthias Mann at the Max-Planck Institute of Biochemistry in Germany and has been working as a staff scientist in the Chemical Biology and Proteomics group at Biogen in Cambridge, Massachusetts since 2014. He applies quantitative proteomics workflows to support early through late stage drug discovery programs, performing experiments to discover and validate drug targets, and determine the mechanism of action of drug candidates.
Presentation: Characterization of human iPSC-derived neurons by transcriptomics and proteomics for drug discovery
To build a credible chain of translation in which the in vitro model captures the molecular mechanism of a clinical condition, it is necessary to have physiologically relevant human cell models that can be produced in a robust and reproducible manner. In the past, this has been particularly difficult to achieve for neurons and other cell types of the central nervous system. It has been shown that overexpression of a single transcription factor, neurogenin 2 (NGN2), can drive differentiation of undifferentiated induced pluripotent stem cells (iPSC) into highly pure populations of cortical excitatory glutamatergic neurons. We adapted this method to produce iPSC-derived neurons with minimal batch-to-batch variability at a scale sufficient to support drug discovery programs in the biomedical industry.
To that end, a doxycycline-inducible expression cassette was genetically integrated into the AAVS1 locus of a healthy control iPSC line, 7189L. After expansion of 7189L iPSC, differentiation was started by overexpressing NGN2 for three days before cells were cryopreserved. Five batches of partially differentiated neurons were recovered, matured, and characterized for consistency in gene expression (RNA-seq), protein expression (nLC-MS/MS) and electrophysiological function by microelectrode array (MEA) technology in a time course experiment over five weeks in culture. Both proteomics and RNA-seq analyses showed progressive neuronal maturation in a manner that was highly consistent between production batches. More than 11,000 proteins were identified in the proteomics study, spanning an abundance range of over seven orders of magnitude. Proteomics data showed an upregulation of proteins associated with neuronal function such as synapse formation and neurotransmitter production throughout the time course. In lines with these observations, time-dependent upregulation of axonal guidance and synaptogenesis were most enriched gene sets in the RNA-seq data. MEA recordings demonstrated robust network activity of the neurons after 28 days of maturation and confirmed the presence of AMPA dependent network bursting, consistent with a pure population of glutaminergic excitatory neurons. In summary, we have established a robust, reproducible and scalable protocol to generate human cortical neurons which were fully characterized by proteomics and transcriptomics for disease modeling and assay development.
Nirupama (Rupa) Pike
Head of Technical Operations, Cell Therapy, Thermo Fisher Scientific
As the Head of Technical Operations at Patheon, Rupa oversees the strategic initiatives and solutions for process development (PD) of GMP grade Cell Therapy products. She spearheads technical training and works closely with partners and clients to conduct technology transfer and process optimization activities. Rupa also leads the efforts to build novel Cell Therapy workflows that will advance PD and GMP manufacturing service offerings at Patheon.
Prior to re-joining Thermo Fisher, she worked as the Director of Cell Manufacturing for UW Program for Advanced Cell Therapy. She was part of the leadership team at WiCell Research Institute that pioneered the early human embryonic and induced pluripotent stem cell research under the leadership of Dr. Jamie Thomson. Rupa developed the Stem Cell Training Course which has served over 800 scientists from 32 US states and 20 countries. At Ligand Pharmaceuticals, she was part of the team that designed novel hematopoietic screening assays for erythropoietin and thrombopoietin in partnership with GlaxoSmithKline, a part of the program that led to development of Promacta®. In her past roles, Rupa has successfully managed R&D laboratory operations, Manufacturing Science & Technology (MSAT) operations, technical training, infrastructure development, customer relations and business development. Rupa holds a Masters degree in Biology from Loyola University and a Doctorate from Harvard University.
Presentation: Transitioning from Cell and Gene Therapy Discovery and Development to Manufacturing - Challenges and Opportunities
Cell and Gene Therapies (CG&T) hold the promise of transforming medicine and human health. The recent commercial success of cell therapy products has generated a tremendous excitement and acceleration of new product development in this arena. Currently, over 400 therapies are in pre-clinical to Phase 3 development, and approximately 1,700 clinical studies are underway globally. As CG&T manufacturing processes evolve to meet regulatory, economic, and patient safety needs, a seamless transition from pre-clinical to GMP manufacturing is critical for their success.
Academic and hospital-based research and development programs play a major role as a source of innovation for new CG&T products. The need for technology transfer and process improvement is foundational as companies acquire licenses for CG&T products from academic centers. The statement that the “process is the product” is particularly true for cell therapies since cells are living pharmaceuticals. The overall success of transitioning the product from development to clinical trials, and ultimately to commercialization, is entirely dependent upon a safe, robust, well-characterized and reproducible process. Scientists can achieve this goal by addressing issues related to raw materials, analytical methods, scalability, personnel training and early incorporation of quality standards. Adopting steps for early process optimization and control will result in manufacturing therapies that meet regulatory requirements and are economically viable at industrial scale.
Soong Poh Loong
Senior Research Fellow, National University of Singapore, Singapore
Co-Founder and Director, Ternion Biosciences, Singapore
Presentation: Human stem cell derived cardiomyocytes for healthcare translation: compound screening and tissue engineering
Human stem cell derived (hSC-derived) cardiomyocytes (CMs) and engineered heart muscle (EHM) offers great potential to model human disease, drug discovery and safety screening. In my research, we routinely culture hIPS cells in animal component free medium followed by mesodermal induction, differentiation and cardiac specification either as cell monolayers or small aggregates. Spontaneous contractions of nascent cardiomyocytes can be observed around Day 8 with subsequent increase in contractile cells over the length of differentiation protocols.
At Ternion, we culture these cardiomyocytes on our custom built OptioQUANT platform for an extended period to obtain sufficient numbers with pronounced contractility prior to subtyping into pacemaker, atrial and ventricular cells. Together with our research collaborators, the platform has been validated and published in the journal, Stem Cells Research & Therapy. For our drug screening purposes, we begin with baseline acquisition of membrane action potentials of the cardiac subtypes, followed by the exposure of drug/compounds at increasing pharmacological concentrations. As OptioQUANT is capable of high-speed acquisitions at sub-second resolution, we were able to report subtle drug induced changes in membrane action potentials from large numbers of human CMs simultaneously that models the drug Mechanism of Action (MoA) in an unbiased manner. Together with OptioQUANT’s expanded capabilities of simultaneous content captures (e.g., force of contractions, calcium imaging, etc), a more robust repertoire of physiological measurements using hSC-CMs can be attained for representation of drug MoA in humans. Therefore using hiPS-CMs obtained from diseased patients (such as Brugada, LongQT, HFpEF, etc) on platforms such as OptioQUANT would recapitulate adverse drug effects in an in vitro setting, enabling accurate disease modeling that could lead to safer precision drug development for pharmaceutical industries.
The heart is not a regenerative organ. Thus, following an injury, cardiomyopathy ensues and progresses into heart failure (HF) if left unchecked. Current pharmacological compounds only delay the progression to HF and do not provide regeneration of the heart. Thus, there is an urgent unmet need to develop therapies to treat cardiac diseases. So, hSC-CMs may be useful in generating 3D constructs of cardiac tissues, such as the engineered heart muscles, for regenerative medicine. However, generating sufficient hSC-CMs to enable functional cardiac tissue engineering is not a small endeavor! In my previous lab (Wolfram Zimmermann’s group) at the Institute of Pharmacology and Toxicology in Goettingen, we placed emphasis on large scale differentation of high quality hSC-CMs, typically obtaining 180 million cardiomyocytes (>98%) weekly, for each tissue engineering project. The CMs were then dissociated and mixed with other supportive stromal cell populations in a hydrogel slurry and pipetted into various geometrical recesses for condensation and compaction. The engineered heart muscles were then used in various applications such as contractility and force measurements in a multi well format for drug screening, or as an epicardial cardiac patch to render contractility in a myocardial infarcted (MI) heart. One interesting engineered tissue model was the development of a biological ventricular assisted device or tissue (BioVAD/T) targeted at provision of support for an entire dilated heart, typically diagnosed in advanced heart failure. The BioVAD further aids in the support by provision of muscle tissue to enable contractility of the diseased heart. In our experiences, no teratomas were observed and the tissues demonstrated long term engraftment and survival in rodents and non human primate animal models. Currently, the BioVAT-HF clinical trial in Goettingen is the 2nd global clinical trial for implantation of in vitro engineered heart muscles into a patient.
Taken together, human stem cell derived cell types provide a viable alternative to animal-based disease modeling leading to human safe precision drug development. Although human stem cell based regenerative tissue engineering has only just begun, the technology holds great promise for therapies of many human diseases in future.
Product Manager Genome Editing, Thermo Fisher Scientific
The speaker is Matthew C. Poling, PhD, Product Manager Genome Editing, Thermo Fisher Scientific. Matt joined Thermo Fisher Scientific in 2015, and has led the development and commercial launch of the TrueTag Donor DNA system as well as the TrueDesign Genome Editor online tool. Matt is also responsible for developing and expanding the Invitrogen CRISPR-Cas9 and TALEN technology portfolio, which includes TrueCut Cas9, Cas9 mRNA and plasmid based CRISPR systems. He works closely with a respected team of R&D scientists on innovative genome editing tools and services. Matt earned his PhD in Biomedical Sciences from UC San Diego.
Presentation: Advanced Tools for Knock-in Genome Editing in iPSCs
Global Product Manager for High-Content Technologies, Thermo Fisher Scientific
Presentation: New enabling technologies for 3D quantitative cellular biology using High-Content Screening
Director, Brain Organoid Core, Weill Cornell Medicine, New York, USA
Richa Singhania is a cross-disciplinary trained scientist with extensive experience in translational cancer research, and her latest research is based on using stem cells and organoids for cancer modeling and drug discovery. Currently, she is spearheading the Starr Foundation Cerebral Organoid Translational Core at Weill Cornell Medicine, New York which integrates organoid and automation technologies to create personalized solutions for brain cancer patients. Richa received a Masters in Biotechnology and PhD in Molecular Biology from University of Queensland, Australia, and postdoctoral training from academic institutions in the UK (University of Nottingham) and USA (UT Southwestern Medical Center and Weill Cornell Medicine). Richa is passionate about bringing precision medicine to the masses, and making preclinical research successful to ultimately improve the lives of people affected by cancer.
Presentation: Organoid models of glioblastoma
Discover the latest advances in generating in vitro 3D models of human glioblastoma (GBM).Dr. Singhania will cover how these organoid-based models for the first time in decades are allowing us to capture the characteristic phenotypic and molecular features of GBM in a dish, to ask fundamental questions of brain tumor development as well as to test and exploit therapeutic vulnerabilities of this cancer in a way that cannot be done in traditional cell lines and animal models. Dr. Singhania will also talk about how these models can be personalized to help direct individual patient treatments.
Professor of Pathology and Laboratory Medicine and Cell and Regenerative Biology at the University of Wisconsin, Madison, USA
Presentation: Advancing pluripotent stem cell technologies for research and therapy of blood diseases
Assistant Professor of Developmental Biology, Washington University School of Medicine, St. Louis, USA
Thor Theunissen grew up in The Netherlands and received his A.B. in Biology from Harvard in 2007. He became interested in stem cells and developmental biology during his undergraduate work in the laboratories of Christine Mummery (Hubrecht Institute) and Stuart Orkin (Harvard Medical School). He completed his graduate studies in José Silva’s laboratory in the Wellcome Trust Center for Stem Cell Research and Department of Biochemistry at the University of Cambridge in 2011. His doctoral thesis focused on the role of the homeodomain transcription factor Nanog in epigenetic reprogramming. As a Sir Henry Wellcome Postdoctoral Fellow in Rudolf Jaenisch’s laboratory at the Whitehead Institute/MIT, Thor developed methods to isolate naïve human pluripotent stem cells. He was appointed Assistant Professor in the Department of Developmental Biology and Center of Regenerative Medicine at Washington University School of Medicine in 2017. He is a recipient of the NIH Director’s New Innovator Award (DP2), the Edward Mallinckrodt Jr New Investigator Award and the Shipley Foundation’s Program for Innovation in Stem Cell Science Award.
Presentation: Understanding human pluripotent states and their applications
The past decade has seen significant interest in the isolation of pluripotent stem cells corresponding to various stages of mammalian embryonic development. Two distinct and well-defined pluripotent states can be derived from mouse embryos: "naïve" pluripotent cells with properties of pre-implantation epiblast and "primed" pluripotent cells, resembling post-implantation epiblast. Prompted by the successful interconversion between these two stem cell states in the mouse system, several groups have devised strategies for inducing a naïve state of pluripotency in human pluripotent stem cells. Here, I will review recent insights into the naïve state of human pluripotency and its applications in biomedical research. The isolation of naïve human pluripotent stem cells offers a window into early developmental mechanisms that cannot be adequately modeled in primed cells, such as X chromosome reactivation and the regulation of hominid-specific transposable elements. Furthermore, recent work from our lab and others indicates that naïve hPSCs have aunique potential to differentiate into extraembryonic lineages, including trophoblast and primitive endoderm. These advances provide a platform to model cell fate decisions in the early human embryo and elucidate the origins of common pathologies afflicting placental development.
Assistant Professor, Emory University School of Medicine, Atlanta, USA
Dr. Zhexing Wen received his PhD training at the Rutgers University in 2008. In 2009, he joined Drs. Hongjun Song and Guo-li Ming’s laboratories at Johns Hopkins University as a postdoctoral fellow. In 2016, Dr. Wen joined the Department of Psychiatry and Behavioral Sciences at Emory University as an Assistant Professor. The research of Dr. Wen’s laboratory centers on understanding the molecular mechanisms underlying neuropsychiatric disorders. In particular, he is interested in using patient-derived induced-pluripotent stem cells (iPSCs) to elucidate the biological functions of causal/risk genetic and environmental factors in neuropsychiatric disorders, identify pathological developmental processes that may contribute to the etiology of these complex diseases, and translate such knowledge into therapeutic targets for developing novel treatments.
Presentation: Molecular dynamics associated with development of human GABAergic interneurons
Chief Technology Officer, Cell Inspire Therapeutics, China
Jiayin Yang is currently the Chief Technology Officer of Cell Inspire Therapeutics, a start-up company in Shenzhen, China that aims to develop candidate therapies for neurodegenerative diseases and rare diseases using stem cell-based models.He received his Ph.D. in stem cells and regenerative medicine from the University of Hong Kong. Dr. Yang has 12 years of research experiences in human pluripotent stem cells (PSCs) and genome editing with custom designed nucleases. In combination with these two cutting-edge technologies, Dr. Yang and his team have generated a series of in vitro models with genome engineered induced pluripotent stem cells (iPSCs) for disease models and drug screening.
Presentation: iPSC-based high throughput platforms for screening novel therapeutics for treatment of Alzheimer's disease and Parkinson’s disease
For Research Use Only. Not for use in diagnostic procedures.