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Science On Demand: A Roundup of Newly Released SOT Webinar Recordings

By James Luyendyk posted 12-22-2022 12:34

  

Many of the webinars hosted by SOT Regional Chapters, Special Interest Groups, and Specialty Sections—collectively known as the SOT Component Groups—are recorded and added to the SOT Video Library so that SOT members and others can watch these valuable presentations at any time. In this blog, you will find a listing of all the recent webinars whose recordings were added to the SOT Video Library.

2022 Computational Toxicology Specialty Section Award Winner Presentations

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Hosted by: SOT Computational Toxicology Specialty Section (CTSS)

Speakers:

  • CTSS Paper of the Year Award recipient Heather Ciallella, Rutgers, the State University of New Jersey—“Revealing Adverse Outcome Pathways from Public High-Throughput Screening Data to Evaluate New Toxicants by a Knowledge-Based Deep Neural Network Approach.” 2021. Environmental Science & Technology 55, no. 15 (August): 10875−87. https://doi.org/10.1021/acs.est.1c02656.
  • CTSS Student Travel Award recipient Xuelian Jia, Rutgers Center for Computational and Integrative Biology—“Mechanism-Driven Modeling of Drug-Induced Liver Injury Using Structural Alerts and an Oxidative Stress Screening Assay”
  • Elsevier/CTSS Postdoctoral Award recipient Adrian Green, North Carolina State University—“Leveraging High-Throughput Screening Data, Deep Neural Networks, and Conditional Generative Adversarial Networks to Advance Predictive Toxicology”
  • Yves Alarie Diversity Award recipient Linlin Zhao, Amazon (honored for work completed while at Genentech Inc.)—“Application of a Matrix Factorization Method for Kinase Data to Support Safety Profiling”

Moderators:

  • Catrin Hasselgren, Genentech, CTSS Past President
  • Patricia Ruiz, CDC/ATSDR



ADME in Liver Disease: Increased Risk of Drug Induced Toxicity

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Hosted by: SOT Drug Discovery Toxicology Specialty Section

Speaker: Nathan Cherrington, PhD, ATS, Associate Dean for Research, University of Arizona

It is well-known that liver diseases such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis can cause local changes in drug transporter and drug metabolizing enzyme expression, localization, and function. However, it is much less clear how liver diseases can affect these proteins in other organs, such as the kidneys. Since the kidneys also are a major organ for elimination, it is speculated that there are liver disease–induced changes in ADME proteins in this organ. As a result, liver disease may lead to increased risk of renal toxicity or other secondary organ toxicity.



Artificial Intelligence Enables Structural Toxicity Testing

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Hosted by: SOT American Association of Chinese in Toxicology Special Interest Group and SOT Computational Toxicology Specialty Section

Speaker: Alexandre Ribeiro, PhD, Senior Scientist, Hovione

This webinar presents a novel image-based artificial intelligence tool for quantifying subtle structural changes in cell-based models. The inputs are a collection of cellular images captured at multiple doses for the drugs of interest and a control set of images with only the vehicle applied. The output is a metric of structural change for each drug dose relative to the control. The technology introduces a new approach for structural toxicity testing that is unbiased and provides a high level of sensitivity that had not previously been possible. Through the process of training deep neural networks, the system learns what features within the images, if any, contribute to the structural changes. The proposed method is agnostic to imaging modality and works for fixed and stained cells (fluorescence images) as well as live cells (bright-field images), enabling drug testing at multiple timepoints.



Combined Effects of Chemical Mixtures Are Predictable for the Whole Transcriptome

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Hosted by: SOT Risk Assessment Specialty Section and SOT Mixtures Specialty Section

Presentation #1

Speaker: Wibke Busch, Group leader iTox (integrative toxicology), Helmholtz Centre for Environmental Research

Toxicogenomic profiles induced by chemical exposures have seldom been systematically considered in mixture contexts. During this talk, I reveal how we predict toxicogenomic effects of a synthetic mixture based on concentration and time-resolved whole transcriptome responses of individual mixture components using an adopted concentration addition approach using the zebrafish embryo model system. After predicting the mixture effects, we perform toxicogenomic measurements for mixture-exposed zebrafish embryos and compare the results with our predictions. These results indicate that the concept reasonable estimates for the effects induced by the mixture exposure on the whole transcriptome, that nonadditive effects were observed only occasionally, and that combined—that is, multicomponent-driven—effects are found for mixture components with anticipated similar, as well as dissimilar, modes of action.

Presentation #2

Speaker: Lucie Ford, doctoral student, Texas A&M University Interdisciplinary Faculty of Toxicology

Human cell-based population-wide in vitro models are proposed as a strategy to derive chemical-specific estimates of interindividual variability; however, the utility of this approach has not yet been tested for cumulative exposures in mixtures. This study aimed to test defined mixtures and their individual components and determine whether adverse effects of the mixtures were likely to be more variable in a population than those of the individual chemicals. The in vitro model comprised 146 human lymphoblastoid cell lines from four diverse subpopulations of European and African descent. Cells are exposed, in concentration-response, to 42 chemicals from diverse classes of environmental pollutants; in addition, eight defined mixtures were prepared from these chemicals using several exposure- or hazard-based scenarios. Points of departure for cytotoxicity are derived using Bayesian concentration-response modeling, and population variability are quantified in the form of a toxicodynamic variability factor (TDVF). We find that 28 chemicals and all mixtures exhibit concentration-response cytotoxicity, enabling calculation of the TDVF. The median TDVF across test substances for both individual chemicals and defined mixtures range from a default assumption (101/2) of toxicodynamic variability in human population to >10. The data also provide a proof of principle for single-variant genome-wide association mapping for toxicity of the chemicals and mixtures, although replication would be necessary due to statistical power limitations with the current sample size. This study demonstrates the feasibility of using a set of human lymphoblastoid cell lines as an in vitro model in order to quantify the extent of interindividual variability in hazardous properties of both individual chemicals and mixtures. The data indicate that population variability of the mixtures is unlikely to exceed that of the most variable component, and that similarity in genome-wide associations among components may be used to accrue additional evidence for the grouping of constituents in a mixture for cumulative assessments.



Considerations regarding Nonhuman Primate Use in Pharmaceutical Development

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Hosted by: SOT Biotechnology Specialty Section and SOT Regulatory and Safety Evaluation Specialty Section

Speaker: Ronald Wange, PhD, Associate Director for Pharmacology and Toxicology, US FDA/CDER

Dr. Wange’s presentation focuses on approaches to limit the use of nonhuman primates in drug development. The first half of the talk provides an overview of the guidance on “Nonclinical Considerations for Mitigating Nonhuman Primate Supply Constraints Arising from the COVID-19 Pandemic,” which was issued as final guidance earlier this year under the US Food and Drug Administration’s COVID-19 public health emergency authority. The second half of the presentation focuses on alternatives to nonhuman primates for assessing the risks of biotherapeutic proteins to embryofetal and postnatal development. An overview of existing guidance that supports use of alternative in vivo approaches and weight of evidence analyses for assessing developmental toxicity risk is provided. He also provides an assessment of the degree to which non-nonhuman primate sources of information have been leveraged for assessing embryofetal and postnatal development through an analysis of the sources of nonclinical data that have been used to inform section 8.1 of the US product labels for biologics approved by CDER over the last several years.



The Ethics of Conducting Toxicological Research and Communicating Novel Findings

Hosted by: SOT Sustainable Chemicals through Contemporary Toxicology Specialty Section and SOT Ethical, Legal, Forensics, and Social Issues Specialty Section

Toxicologists, safety scientists, and risk assessors must convey the substance and importance of their work to non-toxicologists, but often the general public is skeptical, prone to questioning a scientist’s credibility due to mistrust, biases, censorship, and perceived conflicts of interest and issue advocacy. In this three-part webinar series, which features two speakers per webinar, these topics will be addressed through the lens of emerging scientific research and toxicological concerns. The speakers will provide insight drawn from their experiences and give pointers on how toxicologists can earn trust, particularly as related to the assessment of novel scientific and sustainable innovations. This series is organized and.

Webinar #1: Combating Censorship and Vilification

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This webinar highlights recent examples of censorship of inconvenient viewpoints in toxicology (or “consensorship”), the importance of credibility and due diligence as expert witnesses in toxicology, and how to combat vilification by focusing on the science.

Presentations:

  • “Censorship and Issue-Specific Advocacy: Is ‘Consensorship’ the New Paradigm?”

Chris Borgert, President and Principal Scientist, Applied Pharmacology and Toxicology, Inc.

  • “Expert Witness Testimony and Ethics: Science over Advocacy”

Laura Plunkett, Managing Partner, Biopolicy Solutions, LLC

Webinar #2: Toxicologists Can Be Trusted through Integrity and Transparency

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This webinar provides tips for communicating the role of toxicologists to the general public—and why we can be trusted—and discusses the importance of scientific integrity and transparency, including how to disseminate your knowledge effectively.

Presentations:

  • “Who Are Toxicologists, and How Are They Different from My Medical Doctor?”

Michael Dourson, Director of Science, Toxicology Excellence for Risk Assessment (TERA)

  • “Knowledge Mobilization, Scientific Integrity, and Transparency”

Wendelyn Jones, Executive Director, Institute for the Advancement of Food and Nutrition Sciences (IAFNS)

Webinar #3: Avoid Being Toxicology’s Worst Enemy

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This webinar provides tips for interacting with the press to share your novel findings and for how to leverage the applied ethics framework and be a steward of scientific integrity.

Presentations:

  • “The Press Is Not Your Enemy! How to Engage and Interact with the Press”

Janet Raloff, Editor, Science News Media Group

  • Applied Ethics Analyses of Bias, Conflict of Interest, Censorship, and Issue Advocacy

Lyle Burgoon, Executive Chairman and Chief Scientific Officer, Raptor Pharm & Tox Ltd.



Evaluations of Epidemiology and Human Studies for Risk Assessment Recording

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Hosted by: SOT Risk Assessment Specialty Section

Speakers: Rachel Shaffer, PhD, US EPA; and Rebecca Nachman, PhD, US EPA

Designed for early career scientists, this webinar introduces the general principles behind evaluating epidemiological and human health data and those that are key to gathering data that can be used in human health and ecological risk assessment.



Generic Pharmacokinetic Models for Mother-to-Offspring Transfer of Chemicals

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Hosted by: SOT Risk Assessment Specialty Section and SOT Biological Modeling Specialty Section

Speaker: Dustin F. Kapraun, PhD, US EPA

Life-Stage specific considerations for evaluation of susceptibility to chemical exposures have always been challenging. Dr. Kapraun’s development of this dosimetry model provides refined characterization of ADME for important life stages and should be of keen interest to both Specialty Sections.



Metabolic Adaptation of Macrophages as Mechanism of Defense against Crystalline Silica

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Hosted by: SOT Occupational and Public Health Specialty Section

Speaker: Antonella Marrocco, MD, PhD, Harvard School of Public Health

This study contrasts mitochondrial and metabolic alterations induced by LPS and silica on macrophages and correlates them with macrophage viability and cytokine production, which are central to the pathogenesis of silicosis. Using state-of-art instrumentation (high-resolution respirometer and LC-HR-MS), we determine the effects of silica and LPS on mitochondrial respiration of murine macrophage cell lines RAW 264.7 and IC-21, showing that silica induces metabolic reprogramming of macrophages. Silica, as well as LPS, enhances glucose uptake and increases aerobic glycolysis in macrophages. However, in contrast with LPS, silica affects mitochondria respiration, reducing complex I and enhancing complex II activity, to sustain cell viability, associated with reductions of TCA cycle intermediates, including succinate, itaconate, glutamate, and glutamine. In addition, such silica-induced metabolic adaptations do not correlate with IL-1b or TNF-a production but with the suppressed release of IFN-b. Our data highlights the importance of complex II activity and tricarboxylic acid cycle remodeling to macrophage survival and cytokine-mediated inflammation in silicosis.



Overview of Bioinformatic Sequence Analysis and Applications in Toxicology

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Hosted by: SOT Arab Toxicologists Association Special Interest Group and SOT Computational Toxicology Specialty Section

Speakers: Ahmed Abdelmoneim, BVMS, MSc, PhD, Louisiana State University; and Tamer Mansour, MBChB, MS, PhD, University of California Davis

Next-Generation sequencing (NGS) and bioinformatic technologies enable new directions to address research questions that could not be previously considered due to cost/time prohibiting factors and the lack of molecular information. In the field of toxicology, NGS and bioinformatics help us gain a great deal of insight on chemical-induced proteome-, genome-, and transcriptome-wide effects and discover novel biomarkers of toxicant exposure and effects. However, to exploit the full potential of these technologies in toxicological studies, researchers need to learn more about their applications and limitations.

In this webinar, Dr. Abdelmoneim and Dr. Mansour provide an overview on the different branches of bioinformatics and their applications in toxicological research. They discuss how to design your first bioinformatic study and points to consider. They also present a detailed description of how bioinformatics tools are used to analyze datasets associated with a toxicological investigation.



Ramalingaswami Re-entry Fellowship: Opportunity for Returning Scientists

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Hosted by: SOT Association of Scientists of Indian Origin Special Interest Group

Speaker: Ashutosh Srivastava, Discipline of Biological Engineering, India Institute of Technology Gandhinagar

Many foreign students and postdocs come to the US each year to get trained in the field of toxicology and related scientific disciplines. While some of them venture ahead to establish a career as a toxicologist in the United States, many seek other avenues closer to home. The Ramalingaswami Re-entry Fellowship is one such avenue; this fellowship is awarded by the Government of India Ministry of Science & Technology Department of Biotechnology. The goal is to attract high-quality Indian scientists working abroad to pursue their research interests in life sciences, biotechnology, and related areas in India.



Wildfires and the Urban Interface

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Hosted by: SOT Inhalation and Respiratory Specialty Section

Speakers: Olorunfemi “Femi” Adetona, Associate Professor, Ohio State University College of Public Health Division of Environmental Health Sciences; and Amara Holder, Mechanical Engineer, US EPA/ORD

Wildfire smoke is a health hazard for emergency responders, cleanup workers, outdoor workers, and the public. Evidence indicates both pulmonary and extra-pulmonary health effects. The talk by Dr. Femi Adetona discusses the evidence and vulnerabilities relating to the adverse effects of wildfire smoke exposures. It is a serious global public health issue that impacts communities for days, weeks, or even months every year. The presentation by Dr. Amara Holder covers what is known about the chemical composition of wildfire smoke and explores its impact on air quality.

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