SC9: Evaluating and Characterizing In Vitro Models of Drug Toxicity
WEDNESDAY, JUNE 19 | 6:15-9:15pm (DINNER PROVIDED)

ABOUT THIS COURSE:

This short course will focus on ways to evaluate and characterize which in vitro model of drug toxicity is best suited to understand the mechanism and extent of drug toxicity involved. Topics will include a general overview of the different types of in vitro models available to assess drug toxicity, what are some of their inherent strengths and limitations, and what factors need to be considered when deciding which model to use. Those scientists involved in medicinal chemistry, DMPK, safety pharmacology and toxicology will benefit from this overview by understanding some aspects of how safety assessments are made.

COURSE AGENDA:

Asking too much of in vitro models (broad vs. focused/targeted questions):

  • Landscaping performance vs other models
  • Cell lines vs primary cultures:
    • stable vs changing gene expression
    • human vs. animal cell lines
  • Models of cellular differentiation and advantages

Beyond morphology:

  • Gene expression
  • High-content imaging
  • Biomarker analysis
  • In vitro toxicity endpoints are relative - need to consider:
    • Concentrations
    • Time
    • Other treatment conditions
  • Throughput needs, extent of assay qualification, and statistical considerations for assay predictivity

INSTRUCTOR BIOGRAPHIES:

Van_Vleet_TerryTerry Van Vleet, Ph.D., DABT, Head of Molecular and Computational Toxicology, Department of Preclinical Safety, Abbvie

Dr. Van Vleet received a Bachelor’s degree in Zoology from Weber State University and a doctorate in Toxicology studying mechanisms of carcinogenesis and metabolic activation of carcinogens, at Utah State University. His postdoctoral training was at the Medical University of South Carolina, studying mechanisms of renal toxicity with an emphasis in mechanisms of mitochondrial dysfunction. Dr. Van Vleet is a Diplomate of the American Board of Toxicology. He worked at Bristol Myers Squibb in Mt Vernon, Indiana, for 11 years in positions of increasing importance culminating as the Head of the Molecular and In Vitro Toxicology Group. Currently he works at Abbvie in Investigative Toxicology and Pathology (Preclinical Safety) where he is responsible for the Molecular, Genetic, and Computational Toxicology groups. During his career in industry, he has served as a Drug Safety Project Representative, Study Director, and Study Monitor for numerous toxicology programs. He has also identified/characterized numerous mechanisms of toxicity and has been responsible for developing novel molecular assays for evaluating potential mechanisms of toxicity using a number of computational, analytical chemistry, molecular biology, and biochemistry techniques.

Proctor_WillWill Proctor, Ph.D., Senior Scientist, Head of Investigative Toxicology, Department of Safety Assessment, Genentech

Dr. Will Proctor is the Head of Investigative Toxicology in the Department of Safety Assessment at Genentech. Prior to joining Genentech in 2013, Will earned his PhD in Pharmaceutical Sciences from the University of North Carolina at Chapel Hill in the laboratory of Dr. Dhiren Thakker with a focus on drug transport and pharmacokinetics. He then performed postdoctoral training at the NIH in laboratory of Dr. Lance Pohl, focusing on immune mechanisms of drug-induced liver injury (DILI). His research interests in mechanisms of DILI continued at Genentech, where his group focuses on qualifying new in vitro models to predict and characterize hepatotoxicity risk.