- 疾病模型及新药发现的iPS细胞 -

With advances in reprogramming and differentiation technologies, as well as with the recent availability of gene editing approaches, we are finally able to create more complex and phenotypically accurate cellular models based on pluripotent cell technology. This opens new and exciting opportunities for pluripotent stem cell utilization in early discovery, preclinical and translational research. CNS diseases and disorders are currently the main therapeutic area of application with some impressive success stories resulted in clinical trials. Cambridge Healthtech Institute's Third Annual iPS Cells for Disease Modeling and Drug Discovery conference is designed to bring together experts and bench scientists working with pluripotent cells and end users of their services, researchers working on finding cures for specific diseases and disorders.

Final Agenda

Tuesday, June 19

7:30 am Registration Open and Morning Coffee


8:15 Chairperson's Opening Remarks

Peter Reinhardt, PhD, Head, Cell Programming and Transduction, Technology Core,

Neuroscience Discovery, AbbVie

8:20 Application of Disease-Specific iPS Cells to Increase the Success Rate of Drug Discovery

Asano Asami-Odaka, PhD, Associate Director, Ikeya Project, T-CiRA, Regenerative Medicine Unit, Takeda Pharmaceutical Company Limited

Recent synergistic advancement of human iPSC-derived cellular models and relating technologies has enabled to increase the success rate of drug discovery. Not only in phenotypic screenings but also in target validation studies, such strategies have influenced our early decisions. I will show some study examples which used genome-edited or patient-derived iPSCs, with brief introduction of T-CiRA program.

8:50 Strategies to Generate hiPSC-Derived Neural Cells for Robust in vitro Disease Modeling

Peter Reinhardt, PhD, Head, Cell Programming and Transduction, Technology Core, Neuroscience Discovery, AbbVie

The human induced pluripotent stem cell (hiPSC) technology promises to revolutionize the discovery of drugs and treatments against neurodegenerative diseases. However, differentiation protocols into affected neural cells are often not suited for the generation of large in vitro models. We will discuss several examples of how existing and novel protocols for the differentiation of hiPSCs into disease-affected neurons can be transformed into scalable and robust assays fit for purpose.

9:20 iPSC-Based Disease Modeling to Advance Diabetes Drug Discovery

Melissa Thomas, MD, PhD, Medical Fellow, Diabetes and Complications, Eli Lilly and Company

We can generate β-like pancreatic cells that are fully functional as proven by either in vitro or in vivo studies. This novel proof-of-concept stem cell technology brings new expectations on applying stem cell therapy for diabetes mellitus in clinical settings.

9:50 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing


10:35 Single Cell Models of Human Cardiac Development and Disease

Ibrahim Domian, MD, PhD, Assistant Physician, Massachusetts General Hospital, Assistant Professor of Medicine, Harvard Medical School

Human Pluripotent Stem Cell-Derived Cardiomyocytes (hPSC-CMs) have been proposed as a robust cell source for human disease modeling and drug discovery. However, hPSC-CMs cultured in vitro are highly heterogeneous in lineage commitment and metabolic maturation limiting their application. To address this, we have developed novel strategies to simultaneously assess gene expression and cell physiology in a multiplexed fashion at single living cell resolution for the study of metabolic cardiovascular disease.

11:05 KEYNOTE PRESENTATION: From Stem Cells to Kidney Organoids to Disease Modeling

Joseph Bonventre, MD, PhD, Chief of the Renal Unit, Director of the Bioengineering Division, Brigham and Women's Hospital

This talk will describe current protocols for generation of kidney organoids from pluripotent embryonic stem cells and induced pluripotent stem cells (iPSCs), describe the use of these organoids for disease modeling, and describe initiatives to develop innovative approaches to replacement of renal function in humans.

11:35 Human iPSC-Derived Cardiac and Neural Systems and Novel Tools to Drive Preclinical Development

Gregory Luerman, PhD, Technical Director, Ncardia

Drug development is witnessing a shift from conventional target-based drug discovery to a more phenotypic approach, which is enabled by the development of more physiological cellular tools. Here we provide several case studies that utilize human induced pluripotent stem cell-derived cardiomyocytes, neurons, and novel tools within this space. These systems offer a flexible, highly translational and typically more predictive cellular environment than immortalized cell lines or even primary rodent models.

12:05 pm Session Break

12:10 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:40 Session Break


1:15 Chairperson's Remarks

Ibrahim Domian, MD, PhD, Assistant Physician, Massachusetts General Hospital, Assistant Professor of Medicine, Harvard Medical School

1:20 Leveraging Stem Cell Technology to Fuel Drug Discovery for Neurodegenerative Diseases

Carlo Cusulin, PhD, Senior Scientist, Disease Relevant Cellular Assays, Chemical Biology, F. Hoffmann-La Roche

Drug discovery for neurodegenerative diseases presents several challenges because of the complexity of these disorders and the scarcity of reliable and translatable models. iPS technology offers the possibility to produce the relevant cell types (i.e., neurons, microglia, astrocytes) and introduce disease stimuli to obtain an in vitro system amenable for screening. We focused on generating models of Alzheimer's disease, starting from patient-derived iPSCs and assessing the effect of disease-modifying compounds.

1:50 iPSC Derived Neurons and Microglia for in vitro Pharmacology

Johannes Grosse, PhD, Director, Neuroscience Drug Discovery/Alliances, Takeda

The discrepancy between the massive private and academic investments in drug discovery for neurological and psychiatric diseases and the small and still declining number in novel drug approvals is a clear indicator for the unique challenges of the field. Those have been identified at all phases of drug discovery from target validation and hypothesis via pre-clinical models for pharmacological tests to the design of clinical trials, use of biomarkers and regulatory affairs.

2:20 Advanced Physiologically Relevant hiPSC-Based Platforms for Drug Discovery

Fabian Zanella, Director, Research & Development, StemoniX

We present human induced pluripotent stem cell (hiPSC)-based platforms which were structurally engineered with greater physiological relevance aimed to elevate performance in drug discovery applications. microBrain® 3D comprises cortical neural spheroids that feature high functionality with robust spontaneous activity and expected responses to established neuromodulators. microHeart® allows cardiomyocytes to adopt cell geometries and intercellular organization that resemble native heart tissue, translating into differential pharmacological response to known cardioactive compounds.

2:35 Sponsored Presentation (Opportunity Available)

2:50 Refreshment Break in the Exhibit Hall with Poster Viewing

3:30 Modeling ALS with Patient Specific iPSCs

Shila Mekhoubad, PhD, Scientist II, Stem Cell Research, Biogen

Advances in stem cell biology and neuronal differentiations have provided a new platform to study ALS in vitro. Here we will describe our use of induced pluripotent stem cells (iPSCs) from patients with familial ALS to establish new models and tools that can contribute to the development and validation of novel ALS therapeutics.

4:00 All-Optical Electrophysiology for Neuroscience Drug Discovery

Graham Dempsey, PhD, Vice President, Research and Development, Q-State Biosciences

Human induced pluripotent stem (iPS) cell-based models have become a powerful approach to disease phenotyping for drug discovery applications. We have created an optogenetic platform called Optopatch that rapidly and robustly characterizes the electrophysiological response of iPS cell-derived neurons. Our approach provides an information-rich readout of pharmacological changes in both intrinsic neuronal excitability and synaptic transmission with single-cell precision and dramatically improved throughput.

4:30 PANEL DISCUSSION: iPSC-Based Neurodegenerative Disease Modeling

Moderator: Johannes Grosse, PhD, Director, Neuroscience Drug Discovery/Alliances, Takeda

Human neurodegenerative disorders are among the most difficult to study. This panel will discuss existing and future models for major neurodegenerative diseases.

· How do we establish that phenotypes "in a dish" are relevant to the patient's disease?

· Does the relative immaturity of neurons in the dish matter and, if so, what do we do about it?

· What are the major technical barriers to high-throughput screening of iPSc-derived neuronal models?

· Does the technology circumvent the need for rodent preclinical neurodegenerative disease models?

5:00 Find Your Table and Meet Your Moderator

5:05 Interactive Breakout Discussion Groups

This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas and active networking.

Modeling Neurodegenerative Disorders for Drug Discovery and Development

Bilada Bilican, PhD, Investigator II, Neuroscience, Novartis Institutes for BioMedical Research (NIBR)

  • In vitro correlates of complex neurodegenerative diseases.
  • How to model apparently sporadic neurodegenerative disorders
  • Advanced cellular models - how to address cell-autonomous vs. non-cell autonomous mechanisms of neurodegeneration
  • Phenotype- vs. target-based drug screening

Infrastructure and Strategy for iPS Cell Based Drug Discovery

Asano Asami-Odaka, PhD, Associate Director, Ikeya Project, T-CiRA, Regenerative Medicine Unit, Takeda Pharmaceutical Company Limited

Chee Yeun Chung, PhD, Scientific Co-Founder and Associate Director, Discovery Biology, Yumanity Therapeutics

  • Technology advances
  • Phenotypic screenings applications
  • Target validation studies

5:45 Reception in the Exhibit Hall with Poster Viewing

7:00 Close of Day

Wednesday, June 20

7:45 am Registration Open and Morning Coffee


8:25 Chairperson's Remarks

Chee Yeun Chung, PhD, Scientific Co-Founder and Associate Director, Discovery Biology, Yumanity Therapeutics

8:30 Building a Robust Stem Cell-Based Discovery Platform for Neurodegenerative Diseases

Chee Yeun Chung, PhD, Scientific Co-Founder and Associate Director, Discovery Biology, Yumanity Therapeutics

Phenotypic screening in neurons and glia derived from patients is now conceivable through unprecedented developments in reprogramming, transdifferentiation, and genome editing. We outline progress in this nascent field, but also consider the formidable hurdles to identifying robust, disease-relevant and screenable cellular phenotypes in patient-derived cells. We illustrate how analysis in the simple baker's yeast cell Saccharaomyces cerevisiae is driving discovery in patient-derived neurons, and how approaches in this model organism can establish a paradigm to guide the development of stem cell-based phenotypic screens.

9:00 Functionalization of Schizophrenia GWAS Variants by High-Throughput Differentiation of Human Induced Pluripotent Stem Cells

Bilada Bilican, PhD, Investigator II, Neuroscience, Novartis Institutes for BioMedical Research (NIBR)

Schizophrenia is a complex multifactorial and polygenic disorder, with both rare and common genetic variants contributing to disease risk. Genome-wide association studies (GWAS) have highlighted a large number of genetic variants with potential disease association, but validation and prioritization of risk genes remains a challenge.

9:30 Sponsored Presentation (Opportunity Available)

10:00 Coffee Break in the Exhibit Hall with Poster Viewing


10:45 A 3D Culture Model of Alzheimer's Disease: Towards a Cure-in-a-Dish?

Doo Yeon Kim, PhD, Assistant Professor of Neurology, Genetics and Aging Research Unit, Massachusetts General Hospital / Harvard Medical School

Recently, we developed a novel 3D human neural culture model of Alzheimer's disease (AD) that recapitulates key pathological markers of AD. In this presentation, I will show our recent progress including 1) improved 3D culture models based on single-clonal hNPCs and microfluidic devices, 2) mechanistic studies to dissect pathogenic cascades that lead to NFT and neuronal death, and 3) our efforts to optimize 3D culture models for mid-throughput AD drug screening against FDA-approved drugs.

11:15 Identification of Axon Growth Promoting Small Molecules Using a High Throughput Phenotypic Assay Exploiting HiPSC Derived Human Motor and Cortical Neurons

Bhagat Singh, PhD, Research Fellow, Neurobiology, Clifford Woolf's Lab, Boston Children's Hospital, Harvard Medical School

We have generated standardized protocols to differentiate motor and cortical neurons from hiPSCs and also have developed a robust, sensitive and reproducible phenotypic neurite outgrowth assay (Z'>0.5) that recapitulates CNS specific growth phenotypes in vitro. This provides us with a means to screen for regeneration-promoting compounds in a high throughput mode.

11:45 Session Break

11:50 Bridging Luncheon Presentation: Nuclear Imaging of Neuroinflammation in Rodent Models of Neurodegenerative Diseases

Tuulia Huhtala, PhD, Head, Biomarkers and in vitro Biology, Discovery, Charles River

Activation of the mitochondrial translocator protein (TSPO) is linked to neuroinflammation, and TSPO ligands can be used for in vivo PET or SPECT imaging. In the current studies, we utilized these ligands to assess the extent of neuroinflammation after lipopolysaccharide (LPS) infusion, following induction of multiple sclerosis (MS) and neuropathic pain.

12:20 pm Dessert and Coffee Break in the Exhibit Hall with Poster Viewing


Partnering for Sustainable Funding

The panel is designed to discuss partnering between various stake holders such as drug discovery startups, VC firms, large pharmaceutical companies and academic labs in order to advance new target discovery and preclinical research. VC companies, and pharma search & evaluation departments will be represented on the panel.

Jens Eckstein, PhD, President, SR One

Barbara K. Sosnowski, PhD, Vice President and Global Head, External R&D Innovation, Pharmatherapeutics and WRD External Partnerships, Pfizer, Inc.

Kevin Bitterman, PhD, Partner, Atlas Venture

Vivian Berlin, PhD, Director of Business Development, Life Sciences, Office of Technology Development, Harvard University

Plenary Technology Panel

Advancing Innovation in Drug Discovery and Translational Research

This year's Plenary Technology Panel features a group of technical experts from life science technology and service companies, who share their perspectives on various trends and tools that will likely change the way in which we traditionally approach preclinical drug discovery and development. Attendees will have an opportunity to ask questions and understand the impact of recent technical advances.

Ashley Rae Kark, MBS, Director, Corporate Relations, Scientist.com

Additional Panelists will be Announced

Sponsorship Opportunities Available

2:30 Refreshment Break in the Exhibit Hall with Poster Viewing

3:10 Close of Conference

Recommended Event Package

Short Course 8: Direct iN Conversion and iPSC Differentiation - Complementary Tools in Human Neural Disease Modeling

Short Course 10: Applications of Artificial Intelligence & Machine Learning in Drug Discovery & Development

Short Course 14: Advanced Bioprinting Strategies for Generation of 3D Tissue Models

Conference: iPS Cells for Disease Modeling and Drug Discovery

Conference: 3D Cellular Models

2018 World Preclinical Congress CAG Brochure icon

* 活动内容有可能不事先告知作更动及调整。