51st Annual Meeting & ToxExpo - Society of Toxicology

Society of Toxicology 2012
Scientific
Symposia
• Cell Signaling in Response to PARP Inhibition and Alkylating
Agent Exposure. Samuel Wilson, NIEHS, Research Triangle Park,
NC.
• Identifying Translational Components of the DNA Damage
Response. Thomas Begley, State University of New York at Albany,
Albany, NY.
• Damage-Specific Pathways for the Regulation of Postreplication
Repair. Karlene Cimprich, Stanford University, Stanford, CA.
• Redundancy and Cross-Talk in Pathways and Functions in DNA
Damage Responses to the Highly Toxic DNA Double-Strand
Break. Richard S. Paules, NIEHS, Research Triangle Park, NC.
Characterizing Toxic Modes of Action
and Pathways to Toxicity
The Thick and Thin of Nuclear Receptors and Nrf2
in Diabetes and Obesity
Monday, March 12, 9:15 AM to 12:00 Noon
Chairperson(s): Angela Slitt, University of Rhode Island, Kingston,
RI, and Lauren Aleksunes, Rutgers University, Piscataway, NJ.
Sponsor:
Molecular Biology Specialty Section
Endorsed by:
Cardiovascular Toxicology Specialty Section
Mechanisms Specialty Section
Molecular Biology Specialty Section
The Thematic Track information can be found on pages 8–9.
Xenobiotic nuclear receptors, such as CAR, PXR, AHR, FXR, and
NRF2 are best known for transcription regulation and induction of
Phase I and Phase II biotransformation enzymes, as well as transporters.
These receptor pathways are of interest because they are
activated by diverse chemicals—drugs, chemicals of environmental
exposure, as well as endogenous chemicals such as hormones and
bile acids. It is well established that there are chemical-receptor
interactions—especially in the liver, which lead to transcriptional
upregulation of gene batteries and result in coordinate regulation
of metabolism and transport. However, recent evidence points to
nuclear receptors and the role for these receptors in diseases related
to metabolic syndrome, dyslipidemia, and glucose homeostasis. As
the incidence of obesity and obesity-related diseases, which culminate
in metabolic syndrome, increase worldwide, understanding
the mechanisms of obesity is of high interest for human health. As
these receptors are targeted by drugs and environmental chemicals,
it is of importance to understand how activators of these xenobiotic
receptors affect aspects of adipocyte differentiation, adiposity, and
pancreatic function in adults, as well as sensitive populations, specifically
pregnant women and children. Our findings will be presented
for various receptor-mediated pathways with regard to various obesity
and diabetes models. Presentations will cover nuclear receptor-mediated
gene induction and research findings related to nuclear receptors
with regard to obesity and diabetes. Finally, findings will be presented
regarding what is currently known regarding nuclear receptor function
in caloric restriction, the practice most recommended to combat
obesity and obesity-related disorders. The information presented will
be useful to those interested in nuclear receptors, aspects of metabolic
syndrome, mouse models of obesity and diabetes, aspects of metabolic
syndrome and drug interactions, therapeutic drug targets, and
environment-obesogen effects.
• A Novel Function of the Xenobiotic Receptor CAR in Obesity
and Type-2 Diabetes. Wen Xie, University of Pittsburgh School of
Pharmacy, Pittsburgh, PA.
• Paradoxical Roles of Nrf2 Activation in Arsenic-Induced
Pancreatic β-Cell Dysfunction and Insulin Resistance. Jingbo Pi,
The Hamner Institute, Research Triangle Park, NC.
• Bile Acid and Nuclear Receptor Signaling in Diabetes and
Obesity. John Chiang, Northeastern Ohio Universities, Rootstown,
OH.
• Hepatobiliary Transporter Regulation in Diabetic Pregnancy:
Influence of Nrf2 and FXR-Shp Signaling. Lauren Aleksunes,
Rutgers University, Ernest Mario School of Pharmacy, Piscataway,
NJ.
• Reversing Obesity and Metabolic Syndrome: Do Nuclear
Receptors Have a Role in Weight Loss? Angela Slitt, University of
Rhode Island, Kingston, RI.
Aberrant Gene Expression in Toxicity
and Disease—Epigenetics and
microRNAs
Toxicological Considerations of Epigenetic
Targets in Product Development
Monday, March 12, 9:15 AM to 12:00 Noon
Chairperson(s): Melissa Rhodes, GlaxoSmithKline, Research Triangle
Park, NC, and Brandon Jeffy, Celgene, San Diego, CA.
Sponsor:
Drug Discovery Toxicology Specialty Section
Endorsed by:
Carcinogenesis Specialty Section
Mechanisms Specialty Section
Molecular Biology Specialty Section
Regulatory and Safety Evaluation Specialty Section
Reproductive and Developmental Toxicology Specialty Section
In recent years, epigenetic factors have been implicated in the etiology
of various diseases including cancers, psychiatric disorders, and
diabetes/obesity. As epigenetic mechanisms have become more extensively
characterized, new opportunities for therapeutic intervention
Thematic Session
70
SOT’s 51 st Annual Meeting