NCATS Advisory Council June 2015 Concept Clearance DEVELOPMENT OF - - PowerPoint PPT Presentation

NCATS Advisory Council June 2015 Concept Clearance

DEVELOPMENT OF STEM CELL- OR IPS CELL-BASED ASSAYS FOR COMPOUND TOXICITY EVALUATION

MENGHANG XIA, PH.D. LILI M. PORTILLA, MPA ANNA ROSSOSHEK, MS, MBA

Description of the Goal

• For the Phase I cont ract , t he goal is t o develop t oxicological

relat ed assays in homogenous format t hat can be used in human st em cell or iPS

• derived cells wit h short t ime

compound t reat ment .

• For Phase II cont ract s, t he goal is t o miniat urize t he assays

int o 384-well and 1536-well plat e format .

Description of the Outcome

• Potential impact?
• Assays wit h various endpoint s using iPS
• derived cells in a

1536-well plat e format will great ly speed up t he capacit y

• f screening environment al chemicals.
• Also, using iPS
• derived st em cells will make t his screening

approach even more relevant and t he dat a more valuable in order t o est ablishing predict ive models of how t hese chemical compounds affect human t issues and pat hways.

Description of the Outcome

• Criteria for evaluating success?
• The number of solicit at ions received wit h innovat ive

approaches.

• Technical achievement in growing and ut ilizing iPS

derived st em cells for HTS in miniat urized assay plat es.

• A viable iPS

/ st em cell assays t hat meet s all t he appropriat e charact erizat ion crit eria, i.e. sensit ivit y, Z’ value >0.5

• Demonst rat es significant ut ilit y of t he assay by

charact erizing it s abilit y t o det ect t he effect s of compounds known t o affect t he pat hway/ cellular phenot ype.

Description of the Initiative

• What is the major obstacle/opportunity to address?
• Using iPS

cells in toxicological screens therefore making them more relevant in-vitro model systems for the future.

• Relevance to the NCATS’ mission?
• These assays would be the basis for screening programs such as the

Tox21 Program and other qHTS initiatives.

• Brief summary of ongoing research/activity in this

area?

• This proposed contract topic is closely related to a previous S

BIR contract topic entitled, “ Assay Development for High-Throughput S creening of Chemicals of Toxicological Concern” which has successfully produced several new assays to be commercialized by small businesses.