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WEDNESDAY, JUNE 8
12:30 pm Registration
1:55 Chairperson’s Opening Remarks
Mark Sandberg, Ph.D., Senior Scientist, Lead Discovery, Amgen, Inc.
2:00 The Challenges of Using Primary Cells in Drug Discovery
Marcie Glicksman, Ph.D., Co-Director, Laboratory for Drug Discovery, Harvard NeuroDiscovery Center, Partners Center for Drug Discovery; Assistant Professor, Neurology, Brigham and Women’s Hospital
The Laboratory for Drug Discovery in Neurodegeneration (LDDN) was established as a model for how academia can apply its research findings to drug discovery. The LDDN has an established track record of progressing projects along the drug discovery pathway, from assay development, screening, and medicinal chemistry on lead compounds for testing candidate drugs in animal models of disease. There is a strong need for more physiological cell-based models of disease. A project directed towards neurodegenerative diseases using primary astrocytes will be highlighted.
2:30 Partially Reprogrammed Cells Exhibit Marked Variation in Gene Expression, Epigenetic State, and Differentiation Potential
Kelvin Lam, Ph.D., Director, High-Throughput Screening, Harvard Stem Cells Inst, Stem Cell & Regenerative Biology, Harvard University
Retroviral transduction with Klf4, Sox2, Oct4, and cMyc reprograms murine somatic cells to a pluripotent state. However, completely reprogramming any cell type remains an inefficient process with the majority of cells reprogramming to intermediate states. Further characterization of partially reprogrammed states may uncover roadblocks to reprogramming and unknown properties of partially reprogrammed cells (piPSC). To this end, we generated multiple clonal piPSC lines. We demonstrate piPSCs populate a unique molecular and epigenetic territory. For the first time, we demonstrate that partially reprogrammed states are capable of differentiation towards specific lineages. The ability to differentiate or reprogram is influenced by the epigenetic properties of each state. In particular, we find obtaining the proper histone modifications on the Nanog promoter presents a critical roadblock to complete reprogramming.
3:00 Phenotypic Primary Cell Screening with Non-Traditional Label Free Technology
Craig C. Beeson, Ph.D., Associate Professor, Pharmaceutical & Biomedical Sciences, Medical University of South Carolina
We demonstrate that primary cells, isolated and maintained in physiologically relevant conditions, can provide robust, functional phenotypic responses. In these cases, respirometry provides a sensitive read out of specific biochemical processes. Primary screening of chemical libraries has been used to identify small molecule leads that can induce mitochondrial biogenesis. Secondary screens confirm the pathways activated by these leads and cheminformatic refinements have led to the development of novel drug leads. It is shown how these strategies have led to the development of agents that prevent photoreceptor loss in a light damage model for retinal degenerative diseases.
3:30 Networking Refreshment Break in the Exhibit Hall
4:30 Identifying Compound Leads for Breast Cancer Stem Cells
Leigh Carmody, Ph.D., Research Scientist, Project Lead, Assay Development, Broad Institute of Harvard and MIT
5:00 Selected Poster Presentation
5:30 End of Day
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