Welcome to SBS 2011 - SLAS

More documents

Recommendations

Info

SBS 17th Annual Conference & Exhibition Advancing the Science of Drug Discovery A Rapid Assay for Identifying New Drug Candidates From Approved Drugs for Repositioning to Treat Giardiasis Catherine Chen, NIH Chemical Genomics Center Giardia lamblia is a human protozoan pathogen that causes diarrheal disease with an annual worldwide prevalence of 280 million. Resistance to conventional drugs has been reported and the search for new drugs is an unmet medical need. We have developed a novel ATP content assay to assess parasite viability during the life cycle stage responsible for establishing host infections. A pilot screen of 4096 pharmacologically active small molecules revealed several approved drugs with novel and selective anti-Giardia properties. These candidate drugs could proceed to clinical trial quickly once their effects are confirmed in animal models. HTS for REST Inhibitors in Neural Progenies of Human ES Cells Anselme Perrier, I-Stem REST is a transcriptional repressor involved in the regulation of multiple cellular transitions including the inhibition of neuronal differentiation in non-neural cell and the transitions from pluripotent to neural progenitor and to mature neuron. Moreover, REST has been reported in epithelial cancer to act as a tumor suppressor. REST-mediated silencing activity is lifted through down-regulation of the protein level and decreased occupancy by REST of target gene promoter. These regulations are coordinated through extensive feedbacks with CREB proteins (cAMP response element-binding protein) and the brainrelated miRNAs, two distinct classes of regulators of neuronal gene expression. Transcriptional dysregulation is central to the pathogenic mechanisms of several neurodegenerative diseases including Huntingtonís disease (HD). One example involving REST is the disruption in HD patients of BDNF, the brain-derived neurotrophic factor observed. BDNF is produced by cortical neurons and required for survival and differentiation of striatal neurons (the type of neurons primarily affected in HD). Normal huntingtin protein is involved in the physiological control of BDNF synthesis and transport in the brain; in HD, both processes are simultaneously disrupted, leading to the translocation of REST to the nucleus where it represses transcription of many important genes. Here, our research objective was to identify drug capable of modulating REST activity in the human brain using neural progenies of human pluripotent stem cell as a convenient and relevant cellular model. We have developed a protocol for the reliable generation of neural stem cells (NSCs) from human pluripotent stem cells (embryonic or induced). These NSCs are self-renewable, bankable, neurogenic and genetically modifiable. NSCs are highly homogenous and can be efficiently differentiated into an almost pure population of neurons upon mitogens withdrawal. Here we report the development of a REST-activity reporter system for high-throughput screening of chemical compounds capable of modulating REST activity in hESC-derived NSCs. REST acts on its target genes via binding to RE1/NRSE (Repressor Element 1/Neuron-Restrictive Silencer Element), a 21 nucleotide consensus binding site found in the promoter of a number of neuronal and non-neuronal genes (potentially 1946 locations in the human genome). We have thus based our reporter system on the control by REST of a luciferase expression cassette via multiple RE1 sites placed upstream of a strong constitutive promoter. This assay effectively reads REST-activity in human neural cells and has been used to screen around 7000 small molecules (including 1120 FDAapproved drugs). Several families of small molecules capable of modulating the reporter signal were identified. Five selected hit-compounds modulating luciferase expression levels in NSCs via specific inhibition of REST-activity are under investigation. Interestingly, one of these compounds had previously been identified as a compound capable of blocking mutant huntington toxicity in rat neurons. 44 | SLAS.org/events/sbs11
Gaylord Palms Resort and Convention Center | March 27–31, 2011 | Orlando, Florida, USA Podium Presentation Abstracts Tuesday, March 29 Track I: Innovations in the Screening Sciences; Session 2: Innovations in Screening Biology: Assays, Techniques & Instrumentation Session Chairs: Jonathan O’Connell, Bristol-Myers Squibb Company Location: Osceola A 9:00 – 9:30 am Plenary: The Evolution of HTS at Bristol-Myers Squibb: Enabling the Support of the Most Relevant Bio-Assays Jonathan O’Connell, Bristol-Myers Squibb Company 9:30 – 10:00 am Etv6-NTRK3, a Constitutively Active Tyrosine Kinase Found in a Variety of Tumors, is Unique in its Mechanism of Transformation Jack Allen, Merrimack Pharmaceuticals 10:30 – 11:00 am High-Throughput Screening With Real-Time PCR: Reducing it to Practice Andrea Weston, Bristol-Myers Squibb Company 11:00 – 11:30 am New Ion Channel Screening Technologies Enabling Development of High Quality and High-Throughput Assays in a Plate-Based Screening Group Juha Kammonen, Pfizer Global Research & Development 11:30 am – 12:00 pm Creating a Holistic Screening Strategy for Label-Free Technology in a Plate Based Screening Group Rachel Russell, Pfizer Global Research & Development SLAS.org/events/sbs11 | 45
Page 1: SBS 17th Annual Conference & Exhibi
Page 4 and 5: SBS 17th Annual Conference & Exhibi
Page 6 and 7: SLAS On-Demand Offers Scientific Ed
Page 16 and 17: Job Seekers SBS 17th Annual Confere
Page 94 and 95:
SBS 17th Annual Conference & Exhibi
Page 96 and 97:
Page 98 and 99:
Page 100 and 101:
Page 102 and 103:
Page 104 and 105:
Page 106 and 107:
Page 108 and 109:
Page 110 and 111:
Page 112 and 113:
Page 114 and 115:
The world’s leading business revi
Page 116 and 117:
Page 118 and 119:
Epigenetic Assays Check Out Our New
Page 120 and 121:
Page 122 and 123:
Page 124 and 125:
Page 126 and 127:
PORTFOLIO: • 700,000 screening co
Page 128:
Page 131 and 132:
Gaylord Palms Resort and Convention
Page 133 and 134:
The Label-Free 384-Well Revolution
Page 135 and 136:
Unlimited speed? The Autobahn - mad
Page 137 and 138:
Use All That SLAS Offers You to Tra
Page 139 and 140:
Page 141 and 142:
Advance Science Achieve Great Thing
Page 143 and 144:
Page 145 and 146:
Page 147 and 148:
Page 149 and 150:
Page 151 and 152:
Page 153 and 154:
Page 155 and 156:
Page 157 and 158:
Page 159 and 160:
show all

Welcome to SBS 2011 - SLAS

Create successful ePaper yourself

Delete template?

Save as template?