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 Second Annual iPS Cells for Disease Modeling and Drug Discovery symposium is designed to bring together experts and bench scientists working with pluripotent cells and end users of their services, as well as researchers working on finding cures for specific diseases and disorders.

Who should attend: Stem cell researchers, drug discovery scientists working with pluripotent stem cells models for drug discovery and preclinical assessment

Final Agenda

Monday, June 12

7:30 am Registration Open and Morning Coffee

KEYNOTE SESSION: MODELING COMPLEX DISEASES TO IDENTIFY NOVEL THERAPIES

9:00 Chairperson’s Opening Remarks

Ulrich Broeckel, M.D., Professor of Pediatrics, Medicine and Physiology, Pediatrics, Medical College of Wisconsin

9:10 Using Induced Pluripotent Stem Cells for Drug Development in Neurology and Psychiatry

Ricardo Dolmetsch, Ph.D., Global Head, Neuroscience, Novartis Institutes for Biomedical Research

This presentation will explain how iPSC-based experimental approaches are being used to address the biological mechanisms underlying psychiatric and neurodegenerative disorders and are helping to inform drug development.

9:40 iPSC-Based Screening Strategy to Identify Novel Drug Candidates

Christoph Patsch, Ph.D., Principle Scientist, Team Lead, Stem Cell Assays, Roche Innovation Center

In preclinical drug discovery, there is an unmet need for novel disease relevant cell-based assays. iPSC technologies offer new opportunities in disease modeling. Here, we present a drug discovery strategy based on primate neuronal cell models that are derived from patient and Cynomolgus monkey iPSCs.

10:10 Coffee Break

PATIENT-DERIVED STEM CELL MODELS FOR PERSONALIZED TREATMENT DEVELOPMENT

10:40 Patient-Derived Stem Cells for in vitro Modeling of Parkinson’s Disease

Birgitt Schuele, M.D., Director for Gene Discovery and Stem Cell Modeling, Translational Sciences, Parkinson’s Institute and Clinical Center

A critical need to advance the field presents the differentiation of Lewy body Parkinson’s disease from other non-Lewy body forms of parkinsonism. This is important because the underlying molecular pathomechanisms, and hence potential therapeutic targets, are unlikely to be similar for both. IPSC technology utilizing donors with high-quality and comprehensive clinical data and eventually with confirmative neuropathology at autopsy is the key for successful interpretation of findings and clinical translation.

11:10 Induced Pluripotent Stem Cell-Derived Cardiomyocytes to Predict Patient-Specific Responses to Drug Treatments

Ulrich Broeckel, M.D., Professor of Pediatrics, Medicine and Physiology, Pediatrics, Medical College of Wisconsin

We will discuss the underlying concepts of phenotypic variation and the impact of genomic variation on common, complex phenotypes in iPSCs. To demonstrate this, we have established 250 iPSC cell lines from the NHLBI HyperGen study. This study represents a bi-racial cohort with extensive data on cardiovascular disease and associated risk factors. We will discuss our approach to analyzing disease phenotypes on a molecular level using iPSC-derived cardiomyocytes.

11:40 Enjoy Lunch on Your Own

MODELS FOR STUDYING NEUROLOGIC AND NEURODEGENERATIVE DISORDERS

1:40 Chairperson’s Remarks

James Kasuboski, Ph.D., Postdoctoral Fellow, Neuroscience, Pfizer

1:50 KEYNOTE PRESENTATION: Learning about Neurodegenerative Disease Using Human Stem Cell-Derived Neurons

Lee Rubin, Ph.D., Professor, Stem Cell & Regenerative Medicine, Harvard University; Director, Translational Medicine, HSCI

A growing body of work suggests that human diseased neurons produced from pluripotent stem cells can reproduce known features of certain neurodegenerative diseases. I will describe work demonstrating that studies using pluripotent cells also have predictive value: they can reveal previously unknown, but important, aspects of the disease process.

2:20 Rapid and Efficient Inducible Neuron Differentiation for High Throughput Pharmaceutical Screening

James Kasuboski, Ph.D., Postdoctoral Fellow, Neuroscience, Pfizer

Recent iPSC advances have allowed for the generation of human neurons for use in assay development and drug discovery. Though various lengthy multi-step methods have been developed to generate neurons, they are too burdensome and inconsistent for effective screening. Our group has generated an inducible one step system to generate homogenous cultures from iPSC lines in a fourth of the time and provide a feasible and affect screening tool.

2:50 Novel Insights into Alzheimer’s Disease Pathogenesis through the Use of iPSC Technology

Tracy L. Young-Pearse, Ph.D., Assistant Professor, Neurology, Brigham and Women’s Hospital and Harvard Medical School

The ability to accurately and systematically evaluate the cellular mechanisms underlying human neurodegenerative disorders such as Alzheimer’s disease (AD) should lead to advancements in therapeutics. Recent developments in human iPSC technology has afforded the opportunity to use human neurons and glia to study cellular changes involved in neurological diseases. Using iPSCs from sporadic and late-onset patients, we have identified candidate signaling pathways contributing to AD pathology.

3:20 Refreshment Break

3:50 Three Dimensional iPSC-Derived Neuronal Model for Alzheimer’s Disease

Weiming Xia, Ph.D., Acting Associate Director of Research, Geriatric Research Education Clinical Center, Bedford VA Hospital

Efforts to model the physiological environment of the Alzheimer’s disease (AD) brain are facilitated by combining two cutting edge technologies to generate three-dimensional (3D) human neuronal culture from induced pluripotent stem cells (iPSC). We created iPSC from blood cells of AD patients and cognitive normal subjects, and we compared proteomics of iPSC-differentiated 3D neuronal culture. Efficacy of a beta-secretase inhibitor was tested in the same system.

4:20 Exploring the Epigenetic and Transcriptomic Signatures of Down Syndrome Using iPSC Derived Brain Cells

Hiruy Meharena, Ph.D., Postdoctoral Fellow, Tsai Lab, Massachusetts Institute of Technology (MIT)

Down Syndrome (DS) patients exhibit a spectrum of pathologies which include heart disease, cancer, craniofacial abnormalities and most predominantly ~99% of DS patients have deficits in memory and learning. However, the molecular mechanism of how triplication of Chromosome 21 elicits cognitive deficits remains unclear. Here we utilize patient derived iPSCs to generate specific cell types of the brain to capture the epigenetic and transcriptomic signatures unique to DS.

4:50 KEYNOTE PRESENTATION: Pitfalls and Promise of Using Human Stem Cells for Studying Disease

Kevin C. Eggan, Ph.D., Harvard Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute

The discovery of human ES and iPS cells now makes it principally possible to produce a limitless quantity of diverse cell types for the study of disease. I will describe both success stories and challenges encountered during our efforts to implement these strategies in the context of studying developmental and degenerative disorders of the nervous system.

5:20 Close of Symposium

6:30 Dinner Short Course Registration