April 22 14:00 Rational Drug Design: First Steps to Avoid Adverse Effects of Drugs in Pregnancy

Speaker：Richard H. Finnell, Professor in the Department of Nutritional Sciences at the University of Texas at Austin

Host：Prof. Mingyao Liu
When：2014-4-22  14:00
Where：Conference Room 534, School of Life Sciences

CV：Richard H. Finnell is a Professor in the Department of Nutritional Sciences at the University of Texas at Austin, and serves as the Director of Genomic Research at Dell Children’s Medical Center. He is also an Adjunct Professor in the Shanghai Institute of Medical Genetics and a visiting scientist at East China Normal University. A pediatric geneticist, he has a distinguished career researching environmentally induced birth defects.  Dr. Finnell’s group applies stem cell technology to the detection of potential teratogenic compounds in efforts to prevent these birth defects, develops mouse models to understand the pathogenesis of the defects, and uses stem cells to approach novel means of treating these disabilities.  During his 30+-year career, he has authored close to 300 publications in journals such as Science, Nature Genetics, Nature Cell Biology, PNAS and Developmental Cell.  His work with murine embryonic stem cells established the dire embryonic consequences of folate deficiency during embryonic development.  His ongoing research efforts are funded by multiple grants from the US National Institutes of Health and the US Environmental Protection Agency.

Abstract：The “gold standard” when it comes to screening candidate molecules for their potential development into pharmaceutical products is the knockout mouse.  Although currently the leading 200 selling drugs in the world target only 46 gene products, the advent of newer genome editing techniques such as Crisper-Cas9 creates the possibility that a vast number of rationally designed medications will be available.  Unfortunately, our ability to test for one of the most serious adverse side effects of any pharmaceutical compound, its inherent teratogenicity, or ability to cause birth defects when exposure occurs in pregnant women, has not evolved to keep pace with these new drug development advances. There remains a considerable knowledge gap regarding the relationship between exposure to pharmaceutical compounds and potential adverse reproductive and developmental health effects. This data gap necessitates the implementation of a new vision for toxicity testing and a restructuring of risk assessment procedures. To this end, it is essential to have a greater appreciation for the underlying principles of Teratology, in order to avoid these tragic consequences.  In the first of a series of presentations on the topic, I will introduce the Six Principles of Teratology, following up with a review of existing drug screening methodologies moving into the use of human and mouse embryonic stem cell models, and ending with proposed studies utilizing 3D printing and multi-dimensional organ culture systems.