Science Inventory

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New approach methodologies (NAMs) refer to any non-animal technology, methodology, approach, or combination thereof that can be used to provide information on chemical hazard and risk assessment that avoids the use of intact animals. A spectrum of&nbsp;in silico&nbsp;models is ne...

Presentation for the Cascade Training Programme: Risk Assessment Courses Reproductive and Developmental Toxicology.

Experimental models that reduce a complex biological system to simpler assays for high-throughput screening (HTS) of large chemical inventories have the benefit of facilitating quantitative evaluation of cellular and molecular responses to chemical perturbation, providing substan...

Biologically inspired multicellular systems models that are fully computable (eg, virtual embryo) can be used to titrate critical phenomena during tissue development, homeostasis, and disease; however, in silico reconstitution of a complex, self-organizing morphogenetic system fr...

Presentation to Symposium in honor of Aldert Piersma&rsquo;s Retirement RIVM Nov 2023

Scientific and practical needs exist for a different way to predict human developmental toxicity with less reliance on animal testing. The term New Approach Methods (NAMs) refers to any technology, methodology, approach, or combination thereof that can be used to provide informat...

Capacity to model and simulate key events in developmental toxicity using computational systems biology and biological knowledge steps closer to hazard identification across the vast landscape of untested environmental chemicals. In this context, we chose cleft palate as a model ...

Hypospadias, one of the most common birth defects in human male infants, is a condition in which the urethral opening is misplaced along ventral aspect of the penis. We developed an Adverse Outcome Pathway (AOP) framework and computer simulation that describes the pathogenesis of...

Presentation of the US EPA's Virtual Tissue Model project using agent-based models (ABMs). ABMs can execute simulations that self-organize cells into high levels of biological structure and function (emergent phenotypes), and simulate perturbations in the system-dose or stage res...

Integrative models are needed to "decode the toxicological blueprint of active substances that interact with living systems" (Systems toxicology). Computational biology is uniquely positioned to capture this connectivity and help shift decision-making to mechanistic prediction.

Virtual tissue models use new computational methods to construct advanced computer models capable of simulating how chemicals may affect human development. Virtual tissue models are some of the most advanced methods being developed today. The models will help reduce dependence on...

Discuss how the US EPA/NCCT is trying to solve the problem of too many chemicals, too high a cost, and too much biological uncertainty.

Technologies used by toxicologists, and the biological questions we ask, have become increasingly sophisticated with the integration of data science and computational intelligence. Computer models allow us to mine big data and synthesize important concepts that can be applied to ...

Technologies used by toxicologists, and the biological questions we ask, have become increasingly sophisticated with the integration of data science and computational intelligence. Computer models allow us to mine big-data and synthesize important concepts that can be applied to ...

New Approach Methodologies (NAMs) for toxicity assessment that are based largely on in vitro data and in silico models provide a path forward to animal-free testing of the potential for developmental and reproductive toxicity (predictive DART). A major science challenge is transl...

Morphogenetic events are driven by cell-generated physical forces and complex cellular dynamics. To improve our capacity to predict developmental effects from cellular alterations, we built a multi-cellular agent-based model in CompuCell3D that recapitulates the cellular networks...

Standard practice for assessing developmental toxicity is the observation of apical endpoints (intrauterine death, fetal growth retardation, structural malformations) in pregnant rats/rabbits following exposure during organogenesis. EPA’s computational toxicology research program...

SYNOPSIS: The question of how tissues and organs are shaped during development is crucial for understanding human birth defects. Data from high-throughput screening assays on human stem cells may be utilized predict developmental toxicity with reasonable accuracy. Other types of ...

Developmental and Reproductive Toxicity (DART) testing is important for assessing the potential consequences of drug and chemical exposure on human health and well-being. Complexity of pregnancy and the reproductive cycle makes DART testing challenging and costly for traditional ...

Hypospadias is a developmental defect of urethral tube closure that has a complex etiology. Here, we describe a multicellular agent-based model of genital tubercle development that simulates urethrogenesis from the urethral plate stage to urethral tube closure in differentiating ...

Presentation at International Conference on Reproductive Biology and Toxicology Oct 2017 on Computational Biology

Presentation at Brazialian Congress of Toxicology on Computational Modeling of Developmental Toxicity: Modeling with Human Pluripotent Stem Cells

Adverse trends in male reproductive health have been reported for increased rates of testicular germ cell tumor, low semen quality, cryptorchidism, and hypospadias. An association with prenatal environmental exposure has been inferred from human and animal studies underlying male...

Thyroid hormones (TH) are critical for normal brain development. Environmental chemicals may disrupt TH homeostasis through a variety of physiological systems including membrane transporters, serum transporters, synthesis and catabolic enzymes, and nuclear receptors. Current comp...

Blood-brain barrier (BBB) development is a complex process invoked by heterotypic cellularization of the embryonic neuroepithelium: vascular invasion from the perineural vascular plexus; neuroprogenitor proliferation, migration and differentiation in the subventricular zone; and ...