Richard is a Professor in the Department of Nutritional Sciences and in the Department of Chemistry and Biochemistry 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 Serves as the head of the CICbioGUNE research institute’s scientific advisory board in Bilbao, Spain, where he also holds a research appointment.
Robert is a partner with TeratOmic Consulting LLC and leads mechanism of action studies for the group. He has studied and conducted birth defect research for more than 15 years. His primary research includes cellular and animal models for testing the toxicity and teratogenicity of industrial chemicals and pharmaceuticals. He is currently the Project Manager for Stem Cell Research at Dell Children’s Medical Center and a Senior Research Scientist in the Department of Nutritional Sciences at The University of Texas at Austin.
Claudia holds an endowed Professorship in Developmental Biology at the Pennington Biomedical Research Center in Baton Rouge, Louisiana, the largest free-standing center for research on nutrition, obesity and diabetes in the United States. Her investigations focus on beneficial and adverse effects of maternal nutrition and metabolic disease during pregnancy, with special emphasis on neural tube defects and skeletal development. She has served for more than 10 years on review panels for the National Science Foundation, the Environmental Protection Agency, and the National Institutes of Health; she has edited a special Issue of Birth Defects Research and is currently an associate editor of the Journal Reproductive Toxicology.
Michel is Full Professor of Human Genetics at Université Paris Descartes and Director of the Department of Laboratory Medicine and Pathology at Hôpital Necker-Enfants Malades. His research focuses on the etiopathogenesis of human congenital malformations. He is the editor-in-chief of the journal Birth Defect Research part A: Clinical and Molecular Teratology.
Steve is a Professor in the Department of Systems Pharmacology and Translational Therapeutics at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia. For more than two decades he has studied the relationships between dis-regulation of folate and B vitamin metabolism and major human pathologies. His research has focused in particular on the adverse interactions between folate-related genetic, biochemical and environmental factors that compromise important biological functions and can lead to neural tube defects and other congenital malformations.
Bogdan is a toxicologist that has been performing teratology study on animal models for 30 years. He is trying to understand why some babies are born with congenital defects while others are healthy and develop normally. The results of his studies not only allow better understanding of how specific birth defects arise but also help to identify the population of humans (having a similar mutation) who may be at higher risk of conceiving a baby with congenital defects. He holds a Research Assistant Professor position at The Dell Pediatric Research Institute, University of Texas at Austin.
TeratOmic Consulting brings together seasoned scientists and clinicians with experience in the area of adverse birth outcomes. Some work in clinical settings, but each has focused on research that tries to understand the underlying science at the heart of birth defects. They know the birth defects literature from clinical and professional, investigative perspectives.
Teratomic consulting can:
–Produce timely birth defects literature reviews and analysis
–Write concise summaries
–Educate other professionals about the nature of serious birth defects
–Serve as expert witnesses in birth defect litigation cases
Professionally, each member works toward a world where preventable birth defects can indeed be prevented. For more information please contact us at firstname.lastname@example.org
Regulation of folate receptor 1 gene expression in the visceral endoderm
Nutrient supply to the developing mammalian embryo is a fundamental requirement. Before completion of the chorioallantoic placenta, the visceral endoderm plays a crucial role in nurturing the embryo. We have found that visceral endoderm cells express folate receptor 1, a high-affinity receptor for the essential micronutrient folic acid, suggesting that the visceral endoderm has an important function for folate transport to the embryo.
118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects
Folic acid taken in early pregnancy reduces risks for delivering offspring with several congenital anomalies. The mechanism by which folic acid reduces risk is unknown. Investigations into genetic variation that influences transport and metabolism of folate will help fill this data gap. We focused on 118 SNPs involved in folate transport and metabolism.
Folate pathway and nonsyndromic cleft lip and palate
Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common complex birth defect. Periconceptional supplementation with folic acid, a key component in DNA synthesis and cell division, has reduced the birth prevalence of neural tube defects and may similarly reduce the birth prevalence of other complex birth defects including NSCLP.
Genetic basis of susceptibility to teratogen induced birth defects
In this review, we attempt to summarize the epidemiological and experimental literature concerning birth defects whose phenotypic expression can be clearly related to the interactions between several select environmental factors and those genetic pathways in which they are most likely to have significant modifying effects.
Association of selected persistent organic pollutants in the placenta with the risk of neural tube defects
Persistent organic pollutants (POPs) have been associated with a wide range of adverse health effects. Our case-control study was performed to explore the association between placental levels of selected POPs and risks for neural tube defects (NTDs) in a Chinese population with a high prevalence of NTDs. Cases included 80 fetuses or newborns with NTDs, whereas the controls were 50 healthy, nonmalformed newborn infants.
Effects on Gastroschisis among Offspring in the National Birth Defects Prevention Study
Exposure to polycyclic aromatic hydrocarbons (PAHs) occurs in many occupational settings. There is evidence in animal models that maternal exposure to PAHs during pregnancy is associated with gastroschisis in offspring; however, to our knowledge, no human studies examining this association have been conducted.
Retinoic acid-dependent signaling pathways and lineage events in the developing mouse spinal cord
Studies in avian models have demonstrated an involvement of retinoid signaling in early neural tube patterning. The roles of this signaling pathway at later stages of spinal cord development are only partly characterized. Here we use Raldh2-null mouse mutants rescued from early embryonic lethality to study the consequences of lack of endogenous retinoic acid (RA) in the differentiating spinal cord.
Gene variants in the folate-mediated one-carbon metabolism (FOCM) pathway as risk factors for conotruncal heart defects
We evaluated 35 variants among four folate-mediated one-carbon metabolism pathway genes, MTHFD1, SHMT1, MTHFR, and DHFR as risk factors for conotruncal heart defects.
Antiepileptic drugs and pregnancy outcomes
The treatment of epilepsy in women of reproductive age remains a clinical challenge. While most women with epilepsy (WWE) require anticonvulsant drugs for adequate control of their seizures, the teratogenicity associated with some antiepileptic drugs (AEDs) is a risk that needs to be carefully addressed.
Thymidylate synthase polymorphisms and risk of conotruncal heart defects
In this study, we investigated whether the two TYMS functional variants (28 bp VNTR and 1494del6) (275 cases and 653 controls) and six selected SNPs (265 case infants, 535 control infants; 169 case mothers and 276 control mothers) were associated with risks of conotruncal heart defects.
Maternal and infant gene-folate interactions and the risk of neural tube defects
Neural tube defects (NTDs) are common, serious malformations with a complex etiology that suggests involvement of both genetic and environmental factors. The authors evaluated maternal or offspring folate-related gene variants and interactions between the gene variants and maternal intake of folates on the risk of NTDs in their offspring.
Transcriptional analyses of two mouse models of spina bifida
Spina bifida is one of the most common of all human structural birth defects. Despite considerable effort over several decades, the causes and mechanisms underlying this malformation remain poorly characterized.
To better understand the pathogenesis of this abnormality, we conducted a microarray study using Mouse Whole Genome Bioarrays which have ~36,000 gene targets, to compare gene expression profiles between two mouse models
A GCH1 haplotype and risk of neural tube defects in the National Birth Defects Prevention Study
Tetrahydrobiopterin (BH(4)) is an essential cofactor and an important cellular antioxidant. BH(4) deficiency has been associated with diseases whose etiologies stem from excessive oxidative stress. GTP cyclohydrolase I (GCH1) catalyzes the first and rate-limiting step of de novo BH(4) synthesis.
The Continuing Challenge of Understanding, Preventing, and Treating Neural Tube Defects
Reviewing the process of neural tube development and how defects in this process lead to NTDs, both in humans and in the animal models that serve to inform our understanding of these processes.
Evaluation of 309 Environmental Chemicals Using a Mouse Embryonic Stem Cell Adherent Cell Differentiation and Cytotoxicity Assay
We evaluated 309 environmental chemicals, mostly food-use pesticides, from the ToxCastTM chemical library using a mouse ES cell platform. ES cells were cultured in the absence of pluripotency factors to promote spontaneous differentiation and in the presence of DMSO-solubilized chemicals at different concentrations to test the effects of exposure on differentiation and cytotoxicity.
A Computational Model Predicting Disruption of Blood Vessel Development
We describe a novel multicellular agent-based model of vasculogenesis using the CompuCell3D modeling environment supplemented with semi-automatic knowledgebase creation. The model incorporates vascular endothelial
growth factor signals, pro- and anti angiogenic inflammatory chemokine signals, and the plasminogen activating system of
enzymes and proteases linked to ECM interactions, to simulate nascent EC organization, growth and remodeling.
Disruption of Embryonic Vascular Development in Predictive Toxicology
This review examines disruption of embryonic vascular development as a potential adverse outcome pathway leading to developmental toxicity. We briefly review embryonic vascular development and important signals for vascular development (local growth factors and cytokines such as vascular endothelial growth factor-A and TGF-beta, components in the plasminogen activator system, and chemotactic chemokines).
A network of 12 leading global health organizations announces the first annual World Birth Defects Day, to be observed March 3, 2015. The purpose of this observance is to raise awareness about the occurrence of birth defects, develop and implement primary prevention programs, and expand referral and care services for all persons with birth defects. Read the article here.
The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) and the Physicians Committee for Responsible Medicine (PCRM) will cosponsor a scientific workshop on Adverse Outcome Pathways: From Research to Regulation. The workshop proposes to explore and discuss how interaction and collaboration among stakeholders can be initiated and maintained so that scientific progress in adverse outcome pathway (AOP) concepts may improve regulatory assessment of chemical toxicity. The Society of Toxicology endorses this workshop.
The meeting will take place from September 3-5, 2014 at the William H. Natcher Conference Center, National Institutes of Health, Bethesda, Maryland, USA. This workshop is free as is the concurrent plenary presentations webcast. Registration for the workshop or webcast along with other information and a preliminary agenda are available at: http://ntp.niehs.nih.gov/go/41374.
Dr. Christopher Austin of the National Center for Advancing Translational Sciences will provide the opening plenary presentation. Days 1 and 2 of the workshop will include 21 symposium presentations in four sessions:
1) Building Upon Other Efforts
2) AOPs Under Development
3) Case Studies: Regulatory Uses for Well-Identified AOPs
4) The Risk Context.
Days 2 and 3 will include three different interactive and rotating breakout groups and each workshop attendee will participate in all three groups:
·Breakout Group 1: The Process of Regulatory Acceptance
·Breakout Group 2: Using AOPS for Regulatory Decisions: Confidence and Criteria
·Breakout Group 3: Taking Qualitative AOPs to the Next (Quantitative) Level.
A poster session will be held at the Natcher Center on September 4 from 6:00 p.m. to 8:00 p.m. Abstracts can be submitted as per the instructions on the workshop website. Junior investigators will have the opportunity to receive travel support for the workshop by submitting a competitive write-up of their work. The workshop steering committee will determine the top abstracts and the winning investigators will present a short plenary talk about his/her poster at an evening poster session/reception. Federal employees are not eligible to receive travel support from the workshop sponsors. The workshop will conclude on the afternoon of September 5 with moderated whole-group discussion and a hands-on demonstration/training of AOP Wiki/Effectopedia provided by Dr. Stephen Edwards of the U.S. Environmental Protection Agency.
The Shadow of Thalidomide: In the 1950s, thalidomide cut a wide swath of destruction across the world, leaving behind thousands of deformed infants, but that was only the beginning of the story.