Program - Society of Toxicology

50 th Anniversary Annual Meeting and ToxExpo
Program Description (Continued)
MONday
Abstract # Abstract #
#26 10:49 DIFFERENTIAL MECHANISMS OF
SUSCEPTIBILITY TO OXIDANT-INDUCED
LUNG DISEASE. ​E. M. Postlethwait.
Environmental Health Sciences, University of
Alabama at Birmingham, Birmingham, AL.
#27 11:25 TARGETING INFLAMMATION AND THE
INFLAMMASOME USING ANAKINRA, A
POTENTIAL THERAPEUTIC AGENT FOR
MESOTHELIOMA. ​B. Mossman. Pathology,
University of Vermont College of Medicine,
Burlington, VT. Sponsor: L. Mantell.
Monday Morning, March 7
9:15 AM to 12:00 NOON
Room 150
Novel Approaches to Preclinical Safety Assessment:
Bridging the Gap between Discovery and the Clinic
through Translational Toxicology
Symposium Session: High Content Imaging—Applications in
Toxicology and Toxicity Testing
Chairperson(s): William Mundy, U.S. EPA, Research Triangle Park, NC,
and Joseph Trask, The Hamner Institutes for Health Sciences, Research
Triangle Park, NC.
Sponsor:
In Vitro and Alternative Methods Specialty Section
Endorsed by:
Molecular Biology Specialty Section
Neurotoxicology Specialty Section
High Content Imaging (HCI) often referred as high content screening
(HCS), combines state-of-the-art microscopy, robotics, and computerassisted
image analysis to measure multiple cellular and sub-cellular
features. The technology produces information (digital images and metadata)
on cellular response or morphological changes at a high level of detail.
Assays are amenable to high-throughput automation generating hundreds of
measurements per cell and millions of data points from a single microtiter
plate. Introduction of this technology in the pharmaceutical industry led to
analysis of cell signaling and processes such as receptor internalization. The
technology has expanded to include applications in angiogenesis, wound
healing, cell cycle regulation, cell death, neurodegeneration, regeneration,
and genotoxicity, etc. Using these approaches, measurements are made at
the single cell or population level. HCI assays are generally conducted using
cell lines, primary cells, and stem cells. Ex vivo tissue and whole organisms
such as Drosophila, C. elegans, and zebrafish can also be imaged providing
knowledge from intact specimens. Novel strategies for toxicity testing
are likely to expand with HCI studies examining biologically significant
cellular perturbations by linking genetic, phenotypic, or functional cellular
changes with adverse outcomes from exposure to environmental chemicals
or pharmaceutical compounds. HCI is likely to become a key technology
for developing toxicity pathway assays as outlined by the 2007 NRC report
Toxicity Testing in the 21st Century: A Vision and A Strategy. Furthermore,
it is now evident toxicology programs in the pharmaceutical industry have
adopted this technology in an effort to expedite the fate of compound
candidate selection in preclinic and clinical trials using key measurements
generated with HCI. Therefore it is important to provide an overview of this
technology and its applications in toxicity testing relative to the HCI field
from academia, biopharma, and government agencies with examples and
case studies to gain knowledge and insight into toxicity pathways.
#28 9:15 HIGH CONTENT IMAGING –
APPLICATIONS IN TOXICOLOGY AND
TOXICITY TESTING. ​W. Mundy. Integrated
Systems Toxicology Division, U.S. EPA, Research
Triangle Park, NC.
9:15 INTRODUCTION. ​William Mundy
#29 9:25 AN INTRODUCTION TO HIGH CONTENT
IMAGING TECHNOLOGIES AND
APPLICATIONS IN TOXICOLOGY. ​O. Joseph
Trask. The Hamner Institutes for Health Sciences,
Research Triangle Park, NC. Sponsor: R. Thomas.
#30 9:45 HIGH CONTENT ANALYSIS OF
CYTOTOXICITY FOR PREDICTION,
MECHANISTIC ELUCIDATION, AND
BLOOD BIOMARKERS OF HUMAN
TOXICITY. ​P. J. O’Brien. University College
Dublin, Belfield, Dublin, Ireland. Sponsor: J. Trask.
#31 10:15 QUANTITATIVE IN VITRO MEASUREMENT
OF CELLULAR PROCESSES CRITICAL
TO THE DEVELOPMENT OF NEURAL
CONNECTIVITY USING HCA. ​J. A. Harrill.
Integrated Systems Toxicology Division, U.S. EPA,
Research Triangle Park, NC.
#32 10:45 BEYOND DECREASING ATTRITION: HIGH
CONTENT IMAGING (HCI) IN GENETIC
TOXICOLOGY. ​E. Rubitski. Genetic Toxicology,
Pfizer, Groton, CT. Sponsor: J. Aubrecht.
#33 11:15 HIGH CONTENT SCREENING (HCS) IN
EARLY SAFETY ASSESSMENT: FROM DATA
TO PREDICTIVE MODELS. ​M. Kansy 1 and
A. Hoffman 2 . 1 Nonclinical Safety, F. Hoffmann-La
Roche Ltd., Basel, Switzerland and 2 Discovery
Technologies, F. Hoffmann-La Roche Ltd., Nutely,
NJ.
11:45 PANEL DISCUSSION/Q&A.
Monday Morning, March 7
9:15 AM to 12:00 NOON
Room 207
Symposium Session: Ribotoxic Stress: Mechanisms and
Models for Human Disease
Chairperson(s): James Pestka, Michigan State University, East Lansing,
MI, and Yuseok Moon, Pusan National University School of Medicine,
Yangsan, Japan.
Sponsor:
Food Safety Specialty Section
Endorsed by:
Immunotoxicology Specialty Section
Mechanisms Specialty Section
Molecular Biology Specialty Section
Many xenobiotics evoke toxicity and cause disease by modifying critical
mitogen-activated protein kinase (MAPK) signaling pathways that regulate
growth, differentiation, and cell survival. A number of plant, fungal,
bacterial, and algal toxins can aberrantly activate the P38, ERK, and JNK
MAPKs by targeting the ribosome via a process termed the ribotoxic stress
response. Examples of ribotoxic agents include natural toxins produced
by plants (ricin), fungi (trichothecenes), bacteria (Shiga toxins), and algae
(palytoxin). These agents can be encountered in food and water and are
of further concern because of their potential use in chemical terrorism.
Cells involved in the innate immunity appear to be particularly sensitive to
ribotoxic stress. Ribotoxic stress is not completely understood but possible
mechanisms activation of intracellular signaling pathways by sensors of
damage-associated molecular patterns (DAMPs) or endoplasmic reticulum
stress. From a translational perspective, exposure of experimental animals
to ribotoxic stressors can result in downstream pathologic sequelae that
remarkably mimic clinical signs associated with inflammatory human
diseases such as acute respiratory distress, ulcerative colitis, IgA nephropathy,
and hemolytic uremic syndrome. To address these issues, our panel of
experts will explore commonalities and differences in upstream mechanisms
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