2009

Division for Toxicology Symposia at EB2009 New Orleans

Symposium 1: Generating Proteomic Diversity in Xenobiotic Biotransformation with Alternative RNA Splicing

Co-Sponsor: Division for Molecular Pharmacology

Chair: Curt Omiecinski

Alternative patterns of intron removal from pre-mRNA transcripts allow the synthesis of multiple mRNAs from a single gene with the potential capacity to encode different proteins. Estimates indicate that >70% of human protein-encoding genes are alternatively spliced. This symposium will explore the mechanisms, detection and direct implications of alternative splicing, with specific reference to the implications of this process in xenobiotic biotransformation.

Genome wide analysis and heritability of alternatively spliced transcripts in humans

Jacek Majewski, Department of Human Genetics, McGill University and Genome Québec Innovation Centre, Québec, Canada

Small molecule approaches for dissecting the structure and function of the RNA spliceosome

Melissa S. Jurica, Molecular, Cell & Developmental Biology, Center for Molecular Biology of RNA, UC Santa Cruz, Santa Cruz, CA

Correcting aberrant splicing patterns in human disease genes with cell penetrating morpholino oligonucleotides

Patrick Iverson AVI BioPharma Inc, Corvallis, OR

Aberrant splicing of human P450 genes as a modifier of drug and chemotherapeutic metabolism

Ullrich Zanger, Institute of Clinical Pharmacology, Stuttgart, Germay

Alternative splicing of the human xenoreceptor, CAR, results in distinct receptor subtypes with unique biological activities

Curt Omiecinski, Ctr Molecular Toxicology & Carcinogenesis, Penn State University

University Park, PA

Symposium 2: The Role of Nuclear Receptors in Lipid Homeostasis

Co-Sponsor: Division for Cardiovascular Pharmacology

Chair: Jean-Marc Pascussi; Co-Chair: Curt Omiecinski

Beyond their role as xenosensors and regulators of drug metabolizing enzymes, more recently, additional roles for the nuclear receptors have been discovered that involve the homeostasis of cholesterol, bile acids, lipid metabolism and glucose regulation. This symposium will explore the newly defined roles for these xenobiotic receptors as regulators of molecular endocrinology.

Nuclear receptor regulation of bile acid homeostasis
John Young-Ling Chiang, NEOUCOM, Departments of Biochemistry/Molecular Pathology
PO Box 95, Rootstown, OH 44272
 

Farnesoid X receptor modulates renal lipid metabolism, fibrosis, and diabetic nephropathy

Moshe Levi, Depts of Medicine, Physiology and Biophysics, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Biomedical Research Building 451, Denver, CO

The nuclear receptor CAR and its role in energy homeostasis

Jodi Maglich Goodwin, Translational Biomarkers and Mechanistic Biology, Pfizer Global Research and Development, MS8118D -3008

Crosstalk of CAR and PXR activation as an effector of lipid metabolism and glucose homeostasis

Jean Marc Pascussi, INSERM U632, Montpellier, France

Symposium 3: The Nrf2-Keap1 system: an emerging key regulator in defense against oxidative stress, chemical toxicity, and disease

Chair: Qiang Ma; Co-Chair: Masayuki Yamamoto

Nrf2: Key to defense against oxidants, electrophiles, radiation and inflammation

Paul Talalay, The Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD

Environmental lung disease and the role of Nrf2

Steven R. Kleeberger, Laboratory of Respiratory Biology, Director, Environmental Genetics Group, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC

Defense against toxic metals and hyperglycemia by Nrf2

Qiang Ma, Receptor Biology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV

Nrf1 and Nrf2 interplay in regulation of stress response

Jefferson Y. Chan, Department of Pathology & Laboratory Medicine, School of Medicine, University of California, Irvine, Irvine, CA

Molecular basis for the Nrf2-Keap1 system function

Masayuki Yamamoto, Tohoku University School of Medicine, Department of Medical Biochemistry, Sendai, Japan

Symposium 4: Exposure to Environmental Agent Alters Epigenetic Homeostasis

Co-Sponsor: Division for Drug Metabolism,

Chair: Max Costa; Co-Chair: Mary Vore

Mounting experimental evidence has demonstrated that epigenetic regulation of gene expression is altered during cancer development and numerous studies show that tumor suppressor genes become silenced by DNA methylation in solid tumors. Recent studies have shown that mutagenic and non-mutagenic carcinogens can effect histone tail modifications and DNA methylation. This symposium will discuss the evidence that chemical carcinogens have the ability to effect both silencing and activating chromatin marks, leading to heritable changes in gene expression that can be tied to the etiology of tumors.

Epigenetics: The New Genetics of Disease Susceptibility

Randy Jirtle, Duke University, Durham, NC

Chromatin remodeling by chromium

Alvaro Puga, University of Cincinnati, Cincinnati, OH

Differentiation of ES cells induced by epigenetic regulation of Pax6

Lou Lu, UCLA, Los Angeles, CA

Epigenetic effects of nickel exposure

Max Costa, NYU School of Medicine, New York, NY

Identifying genome wide DNA methylation patterns and histone modifications in response to benzo[a]pyrene exposure

David Rodenhiser, University of Western Ontario, Ontario, CA

2008

Division for Toxicology Symposia at Past EB Meetings

Division for Toxicology Symposia at EB2008 San Diego

Symposium 1: Development of Inhibitors of the Soluble Epoxide Hydrolase as a Novel Treatment for Hypertension, Vascular Inflammation and End Organ Damage
Chairs: Bruce Hammock and John D. Imig
 
Epoxide hydrolases, from xenobiotic metabolism to pharmaceutical target
Michael Arand, University of Zurich, Zurich, Switzerland

Stabilization of epoxyeicosanoids by inhibitors of the soluble epoxide hydrolase as treatments for hypertension, vascular inflammation and end organ damage
John D. Imig, Medical College of Georgia, Georgia

Genetic polymorphisms of the soluble epoxide hydrolase are associated with risk of stroke and vascular disease.  Darryl C. Zeldin, NIEHS, NIH, NC

Biochemistry, structure and the design of inhibitors for the soluble epoxide hydrolase
Bruce D. Hammock, University of California – Davis, CA

Translation of soluble epoxide hydrolase inhibitors to the clinic.  Heather Webb, Arête Therapeutics

The impact of research on epoxide hydrolases and epoxyeiconsanoids on human health
William B. Campbell, Medical College of Wisconsin, WI
 
Symposium 2: The Emerging Science of Drug Safety
Sponsors: the Divisions for Clinical Pharmacology, Translational Medicine & Pharmacogenomics, Drug Discovery, Development & Regulatory Affairs, Toxicology, Behavioral Pharmacology, Cardiovascular Pharmacology, Drug Metabolism.  Chairs: Darrell R. Abernethy and Judith K. Jones

Introduction.  Darrell R. Abernethy, U.S. Pharmacopeia

Approaches to enhance drug safety in the ambulatory outpatient setting.  Michael Murray, University of North Carolina School of Pharmacy

Identification and evaluation of drug induced disease.  Judith K. Jones, The Degge Group, Ltd. Arlington, VA

European experience with active surveillance methods to identify drug safety problems
Sir Alasdair M. Breckenridge, Medicines and Healthcare Products Regulatory Agency
London, U.K.

Development of informatics to support post-marketing surveillance in the United States
Kenneth D. Mandl, Harvard-MIT
 
Symposium 3: Drug Metabolism, Bioactivation & Chemical-induced Toxicities: Lessons Learned & Contemporary Issues.  Sponsors: Divisions for Drug Metabolism, Toxicology, Clinical Pharmacology, Translational Medicine & Pharmacogenomics, Systems & Integrative Pharmacology.
Chairs: Terrence J. Monks and Kenneth E. Thummel
 
Drug toxicites - Lessons learned.  M.W. Anders, University of Rochester, NY
 
Cytochrome P450 mediated drug bioactivation and idiosyncratic toxicities. B. Kevin Park
University of Liverpool, UK
 
Transporters and drug-induced toxicities. Susan P.C. Cole, Queen's University, Canada
 
Symposium 4: Inflammation: Early Disease Marker, Drug Response Modifier, Therapeutic Target.  Sponsors: Divisions for Drug Discovery, Development & Regulatory Affairs, Clinical Pharmacology, Translational Medicine & Pharmacogenomics,  Molecular Pharmacology, Toxicology, Systems & Integrative Pharmacology, Drug Metabolism.  Chairs: Donald W. Miller and Daniel S. Sitar
 
Inflammation markers as early diagnostic tools and potential drug targets for disease
B. Alex Merrick, NIEHS, NIH, NC

Inflammation and drug idiosyncrasy - Is there a connection?  Patricia E. Ganey, Michigan State University, MI
 
Role of the blood-brain barrier in central nervous system inflammation.  Donald W. Miller
University of Manitoba, Canada
 
Emerging anti-inflammatory therapeutics: Perspectives from the laboratory.  David E. Szymkowski, Xencor, Inc.
 
Emerging anti-inflammatory therapeutics: Perspectives from the clinic.  Robert I. Fox
Scripps Memorial Hospital & Research Foundation, CA
 
Symposium 5: The Promise and Challenges of Pharmacogenetics as a Diagnostic Tool.  Sponsors: the Divisions for Clinical Pharmacology, Translational Medicine & Pharmacogenomics, Drug Metabolism, Systems & Integrative Pharmacology, Toxicology.  Chairs: Steven Leeder and Dan M. Roden
 
The use of pharmacogenetics to optimize cancer chemotherapeutics in children.  William E. Evans, St. Jude Children's Research Hospital, TE
 
Predictive tests for asthma exacerbations and short acting response to brochodilator medication: Use of whole genome data.  Scott T. Weiss, Brigham and Women's Hospital, Harvard Medical School, MA
 
Genetic variation in statin response.  Ronald Krauss,  Children's Hosp. Oakland Research Institute
 
Title TBA.  Herbert Y. Meltzer,  Vanderbilt University Medical Center, TE
 

Symposia at EB 2006 

1)   Cellular and Molecular Pathways of Neurotoxicity:  Relevance to Neurodegenerative Diseases - Jean L. Cadet

2)   Targets of Toxicant Sensitivity in Aging- Harihara Mehendale

3)   Therapeutics and Toxicology of COX-2 Inhibitors - Jim Kehrer

4)   Response to Oxidative Stress by Specific Epithelial Cell Types - Phil Mayeux

Symposia at EB 2007

1)   Toxicology of Nanomaterials - N. Monteiro-Riviere and M. Fariss

2)    Mechanisms of Idiosyncratic Drug Reactions - C. Ju and D. Petersen

3)    Molecular Mechanisms of Chemical Teratogenesis - P. Wells

4)    Toxicogenomic Approaches for Evaluating Drug and Chemical Toxicity - Curt Omiecinski

Symposia at EB 2008

1)    Development of Inhibitors of the Soluble Epoxide Hydrolase - Bruce Hammock and John D. Imig

2)    Role of Transporters in Prevention and Exacerbation of Toxicity - Mary Vore

3)    Mitochondria in Life and Death: From Biogenesis to Autophagy - R. Schnellmann