NOTE: Due to extremely popular demand, advance registration for this symposium is SOLD OUT.

SLAS is pleased to partner with the Sanford-Burnham Medical Research Institute, in collaboration with the Sanford Consortium for Regenerative Medicine and event sponsors Cellular Dynamics International, DiscoveRx and HighRes Biosolutions to present Pioneering Stem Cell Research for Regenerative Medicine, a satellite symposium taking place in conjunction with SLAS2014.

This symposium will impart the latest scientific developments in stem cell research aimed at diagnosing, treating and eventually curing degenerative disease through regenerative treatments. The program will include multiple scientific presentations by leading researchers affiliated with the Sanford Consortium. Program details — including presentation titles, abstracts and presenters — will be available in September.

Access to this unique educational event is FREE to registered participants of SLAS2014. Symposium attendees will receive round-trip bus transportation from the San Diego Convention Center (site of SLAS2014).

NOTE: Due to extremely popular demand, advance registration for this symposium is SOLD OUT.

Event Schedule (subject to change)
Sunday, January 19, 2014
12:30 pm – 4:30 pm

12:30 pm: Buses depart San Diego Convention Center
1:00 pm: Arrival at Sanford Consortium for Regenerative Medicine
1:15-3:30 pm: Scientific Program & Presentations
3:30-4:00 pm: Networking Reception
4:00 pm: Buses return to SLAS2014 at San Diego Convention Center
4:30 pm: SLAS2014 Exhibition Opens (Reception in Exhibition Hall)

Program Details
This event will feature four oral presentations by leading researchers in the field. Speaker and presentation details are as follows:

Cancer Stem Cells: Biologic and Therapeutic Implications
Catriona Jamieson, UCSD

    Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm initiated in hematopoietic stem cells by expression of the BCR-ABL1 fusion oncogene and its protein product, which enhances ABL1 kinase activity. Targeted BCR-ABL tyrosine kinase inhibitors (TKIs), such as Imatinib, and the second generation TKIs like Nilotinib as well as the dual specific SCR and ABL inhibitor Dasatinib have significantly slowed disease progression by eradicating the bulk of BCR-ABL1 expressing cells in the circulation. However, progression to a therapeutically resistant blast crisis (BC) phase is driven by CD34+CD38+Lin- progenitors that co-opt stem cell properties, such as enhanced self-renewal and survival, albeit in a deregulated manner. These leukemia stem cells (BC LSC) harbor altered BCL2, CD44 and beta-catenin splice isoform expression, in some cases as a result of RNA editing driven alternative splice isoform generation. We investigated the role of primate specific RNA editing in malignant reprogramming of progenitors in CML during blast crisis transformation. Whole transcriptome RNA sequencing revealed that progression from chronic phase to blast crisis was associated with increased RNA editing driven by adenosine deaminase associated with RNA (ADAR1), an RNA editase that converts adenosines to inosines which are subsequently read as guanosine bases in RNA usually within the context of a hairpin loop formed by primate specific Alu sequences. Lentivirally enforced ADAR1 overexpression increased myeloid progenitor expansion and ADAR1 knockdown reduced serial transplantation potential of blast crisis progenitors suggesting that ADAR1 plays a critical role in malignant reprogramming by endowing progenitors with self-renewal potential. Current efforts focus on early detection of RNA editing using an ADAR-luciferase reporter assay as well as targeted small molecule-mediated ADAR1 inhibition to prevent malignant reprogramming.

New Reprogramming Approaches to Produce iPSCs and Neural Subtypes Useful for Screening
Kristin Baldwin, Ph.D., Department of Molecular and Cellular Neuroscience, The Scripps Research Institute

    Reprogramming of an accessible cell lineage such as skin or blood into an inaccessible lineage such as induced pluripotent stem cells (iPSCs) or induced human neural subtypes (iNs) offers an exciting new set of tools to enable drug screening and mechanistic studies of human disease, particularly those influenced by human genetic variation. A barrier to the effective use of these cells is unwanted heterogeneity in the differentiation potential or function of cells derived using reprogramming. We have employed whole genome sequencing, TALEN mediated gene targeting, screening of combinatorial antibody libraries and direct induction of neurons using new transcription factor combinations to address the source of variation in iPSCs and identify potentially new methods to produce iPSCs using antibodies in place of transcription factors. In addition we have identified new methods to produce and/or genetically label specific neuronal subtypes that may be useful in screening studies for a range of neurologic disorders.

High Content Screen for Compounds that Modulate Neurite Growth
Anne Bang, Ph.D, Conrad Prebys Center for Chemical Genomics Sanford Burnham Medical Research Institute

    Neurite formation plays a fundamental role in development and remodeling of neuronal networks suggesting that neurite outgrowth and retraction may be useful phenotypic read-outs to develop small-molecule probes to study how these processes are altered in neurological disease. Using human induced pluripotent stem cell (hiPSC) derived neurons we have developed a high content screening protocol to identify small molecules that modulate neurite growth. Readouts include measures of outgrowth and branching with Z-factors greater than 0.5, representing a robust assay. We will present results from screening a collection of ~5000 bioactive compounds, primarily known drugs and well-characterized modulators of known targets, aimed at discovery of pathways not previously known to play a role, and tool compounds for further exploration of underlying biology.

Using Pluripotent Stem Cells to Find Drugs for Alzheimer's Disease
Larry Goldstein, Distinguished Professor, Department of Cellular and Molecular Medicine, and Department of Neurosciences, UCSD School of Medicine; Director, UC San Diego Stem Cell Program; Scientific Director, Sanford Consortium for Regenerative Medicine

    Alzheimer's disease is common and incurable as a result of the failure thus far of every candidate drug that has been tested. One possibility for the complete failure to develop effective drugs for Alzheimer's disease is that the models used for drug development in animals or nonneuronal cells are inadequate. I will discuss the possibility that human induced pluripotent stem cells carrying genetic mutations that cause hereditary Alzheimer's disease can be used to generate neurons with Alzheimer's disease phenotypes that are more reflective of the true human disease. I will discuss recent progress developing assays for such phenotypes that may be suitable for translation into moderate throughput screening systems. Our primary approach is to take advantage of abnormally phosphorylated tau protein caused by genetic duplications of the amyloid precursor protein gene. We have drugs from existing knowledge that inhibit different aspects of proteolytic cleavage that we can use to develop assays that we are adapting for 384 well format.

Click here to read the official press release.

Symposium Sponsors

Cellular Dynamics
Cellular Dynamics International is a leading developer of fully functional human cells derived from induced pluripotent stem (iPS) cells. Our iCell® and MyCell® product lines provide industrial quantities of pure human cells enabling disease modeling, drug discovery, and toxicity testing.
DiscoveRx is a leading provider of next generation drug discovery screening and profiling platforms. With >1000 target-based and primary cell systems, our comprehensive portfolio accelerates the discovery of novel therapeutics in the areas of oncology, autoimmunity, metabolic disease, inflammation, CNS and cardiovascular research.
HighRes Biosolutions
HighRes Biosolutions, Inc. is the leader in the design and construction of innovative robotic systems and laboratory devices used by pharmaceutical, biotech, and academic research laboratories. HighRes offers highly flexible, expandable and modular integrated systems and bench-top devices that are easily configured (and reconfigured) for fast-paced, dynamic laboratories.