Environmental Mutagenesis & Genomics Society

51 st Annual Meeting, Palm Springs, California

September 12-16, 2020 - Renaissance Palm Springs Hotel

Environmental Genomics:
Mechanisms & Approaches
For Genomic Integrity

CLICK ON ORANGE HEADINGS TO EXPAND/COLLAPSE FOR DETAILS

Friday, September 11, 2020

Board Meeting
6:00 PM - 8:30 PM |
EMGS Executive Board Meeting
Andreas Room


 

Saturday, September 12, 2020

7:00 AM - 5:00 PM | Registration
Ballroom Foyer Room

7:00 AM - 5:00 PM | Speaker Ready Room
Cactus Room


Workshop 01

8:30 AM - 4:30 PM |
Advancing the Next Generation of Genetic Toxicology and Cancer Risk Assessment
Chair: Francesco Marchetti, Co-Chair: Robert Young, Young Investigator: Sheroy Minocherhomji
Catalina Room (Registration addon required)

Advances in next-generation sequencing make it feasible to analyze the whole genome of an organism in a matter of days. However, direct sequencing of DNA to evaluate mutagenesis in mammalian genomes is currently not possible with conventional next-generation sequencing because of an error rate (1 error per ~1000 sequenced bases) well above the mutant frequency of normal cell replication (~10-7 to 10-8). In recent years, a set of new sequencing tools, termed collectively as Error Corrected Next Generation sequencing (EC-NGS), have emerged that allow the detection of rare mutations within the heterogenous population of cells (Salk et al 2018; Salk and Kennedy, 2019) . These error-corrected sequencing technologies can be applied in any species/tissue and are poised to revolutionize genetic toxicology. New genomics approaches and paired-ends NGS techniques are also allowing a better understanding of structural variation in the genome (eg, duplication and deletion of large genomic regions), characterization of induced genomic instability and their impact on health (Compagno et al 2017; Garaycoechea et al, 2018) . The primary aim for this workshop is to educate the wider genetic toxicology community on basic methodologies and principles such as EC-NGS and other genomics approaches, including wet lab and bioinformatic approaches available. The workshop will provide an opportunity to learn about the various EC-NGS, paired-end NHS and genomics platforms, understand the critical bioinformatics pipelines needed for extracting and analyzing data generated by these platforms. We will also aim to cover other potential applications of these technologies for elucidating the mechanisms of mutagenesis for regulatory applications, cancer cell heterogeneity and basic biology. The workshop is planned for a one-day meeting to be held in conjunction with the 2020 Annual meeting of the Environmental Mutagenesis and Genomics Society and is aligned with the interests of the HESI EC-NGS and Germ Cell workgroups of the Genetic Toxicology Technical Committee and to the FDA’s predictive toxicology roadmap.

Workshop Agenda:

7:30 AM- 8:30 AM
Registration, light breakfast with coffee/tea

8:30 AM- 8:45 AM
Welcome, opening remarks, purpose of the workshop
Francesco Marchetti, Health Canada

8:45 AM- 10:00 AM
Concept: Unmet Need for Human Cancer Risk Assessment
Title: Landscape for a need to advance preclinical cancer risk assessment of xenobiotics

8:45- 9:10 Improving preclinical cancer risk assessment – a regulatory perspective. TBD
9:10- 9:35 Preclinical hazard identification: Patricia Escobar, Merck & Co.
9:35- 10:00 Alternative to lifetime cancer bioassay: Frank Sistare, Consultant

10:00 AM- 12:00 AM
Concept: New technologies to detect ultra-rare de novo mutants in mammalian genomes
Title: Development, implementation and data analysis of error-corrected sequencing technologies

10:00-10:30 NGS Sequencing introduction – Tom Wilson, Univ Michigan

10:30 AM- 11:30 AM
Coffee Break

11:00-11:30 Review of Error Corrected Sequencing technologies - Jesse Salk and Clint Valentine, TwinStrand
11:30-12:00 Mutagenicity in somatic tissues, technology transfer of Duplex Sequencing: A case study – Bob Young, MilliporeSigma/Bioreliance

12:00 AM- 1:00 PM
Lunch

1:00 PM- 2:15 PM
Concept: Genomic basis for non-clinical prediction of human genotoxicity and cancer risk
Title: Advancing mutagenicity and genome instability testing of xenobiotics

1:00-1:25 Landscape of mutations in mammalian cells – Ludmil Alexandrov’s Group Member, UC San Diego
1:25-1:50 New approaches to assess structural variation in the genome - Tom Wilson, Univ Michigan
1:50-2:15 Biomarkers of Drug Induced Genomic Instability in mammalian genomes - Sheroy Minocherhomji, Amgen

2:15 PM- 2:45 PM
Coffee break and Networking

2:45 PM- 4:00 PM
Concept: Regulatory requirements for implementation of new genomic sequencing endpoints for genotoxicity and cancer risk assessment
Title: Acceptance of Error Corrected Sequencing technologies for regulatory testing

2:45-3:10 Roadmap to Biomarker Qualification – Frank Sistare, Consultant
3:10-3:35 Building an Error Corrected Sequencing community - Kristine Witt, NIEHS
3:35-4:00 The role of HESI in the qualification and acceptance of new biomarkers of drug safety - Syril Pettit, HESI

4:00 PM - 4:30 PM
Panel discussion and audience engagement on topics discussed
Group discussion and closing remarks


Workshop 02
8:30AM - 4:30PM |
Quantitative Interpretation of Genetic Toxicity Dose Response Data for Risk Assessment and Regulatory Decision-making: Current Status, Persistent Challenges, and Emerging Priorities
Chair: Paul White, Co-Chair: Andreas Zeller, Young Investigator:
Madera Room (Registration addon required)

In 2008 Health Canada issued a contract to HESI (Health and Environmental Sciences Institute) that provided funding to create the G4 database, a database containing curated genetic toxicity dose-response data for 4 known mutagens (i.e., ENU, MNU, MMS an EMS). The database constituted the foundation for quantitative analysis that compared and contrasted different methods for interpreting genotoxicity dose-response data. The analyses resulted in two white papers (i.e., Gollapudi et al., 2013 and Johnson et al., 2014) . This foundational work was the basis for formal establishment of the GTTC Quantitative Analysis Workgroup (QAW). Since 2014, the QAW has conducted research dedicated to the establishment of a foundation for routine quantitative interpretation of genotoxicity dose-response data (e.g., White and Johnson, 2016, Wills et al., 2016a, Wills et al., 2016b, Soeteman-Hernández et al., 2016) . Initial work examined the utility of the BMD (Benchmark Dose) approach; moreover, the BMD combined covariate approach for compound potency ranking and MOA investigation. A QAW Workshop held in July 2014 resulted in a May 2016 Special Issue of Mutagenesis that provided an overview of the state of the science regarding quantitative interpretation of genotoxicity dose-response data. Follow-up work, most recently a commentary by White et al. published in the 50th Anniversary Special Issue of EMM (Environmental and Molecular Mutagenesis), highlighted the state of the science, and challenges that are hampering routine use of genetic toxicity dose-response analysis for risk assessment and regulatory decision-making. More specifically, White et al. (2020) noted that there is a need for consensus on CES (Critical Effect Size) for routine use of the BMD approach, and empirical evaluation of the default AF (Assessment Factor) values, also known as Uncertainly or Adjustment Factors, commonly used to determine HBGVs (Health-based Guidance Values). With respect to the latter, a need to empirically determine AF values that are suitable for routine interpretation of in vivo genetic toxicity dose-response data in a risk assessment context. White et al. (2020) also noted a need to develop methods for routine interpretation of in vitro genotoxicity dose-response data. The workshop will (1) provide a brief overview of the state of the science regarding quantitative interpretation of genetic toxicity dose-response data, including a brief overview of the BMD combined covariate approach for potency ranking and MOA investigation, (2) a summary of recent genotoxicity risk assessment case studies, particularly those related the pharmaceutical impurities such as NDMA, (3) an in-depth overview of issues pertaining to developing consensus CES values for genotoxicity endpoints, (4) an in-depth overview of issues pertaining to the determination of effective AF values for routine interpretation of genotoxicity dose-response data for establishment of HBGVs, and (4) a brief overview of issues pertaining to interpretation of in vitro genotoxicity dose-response data in a risk context. The workshop will include two 1hr time slots for structured discussion aimed at delineating action items a next steps.

7:00 AM- 8:00 AM
Registration, light breakfast with coffee/tea

8:00 AM- 8:30 AM
Quantitative Analysis of Genotoxicity Dose-response Data for Risk Assessment and Regulatory Decision-making Where We Are and How We Got Here
Andreas Zeller, Hoffmann-La Roche, Basel, Switzerland

8:30 AM- 9:00 AM
Existing Paradigm for Use of Gentoxicity Data in Chemical Risk Assessment
TBD

9:00 AM- 9:30 AM
Establishing Permitted Daily Exposure Values (PDEs) for Genotoxic Impurities in Therapeutic Products – Current Status and Emerging Priorities
TBD

9:30 AM- 10:00 AM
Coffee break

10:00 AM- 11:30 AM
Structured discussion – action items to advance the acceptance and use of genotoxicity dose-response data for chemical safety testing and risk assessment
All; moderated by Andreas Zeller & Paul White

11:30 AM- 12:00 PM
Determination of Critical Effect Size (CES) Values for Genotoxicity Endpoints – Current Status and Future Directions
Paul White, Health Canada, Ottawa.

12:00 PM- 1:00 PM
Lunch & networking

1:00 PM- 1:30 PM
Empirical Determination of Assessment Factors (AFs) for Calculation of HBGVs (Health-based Guidance Values) for Genotoxic Substances
Alexandra Long, University of Toronto, Toronto, Canada

1:30 PM- 3:00 PM
Structured Discussion - delineation of milestones and action items regarding determination of CES and AF values for genotoxicity endpoints
All; moderated by Paul White & Andreas Zeller

3:00 PM- 3:30 PM
Coffee Break

3:30 PM- 4:00 PM
Genotoxicity Risk Assessment without Animals - Quantitative Interpretation of In Vitro Genotoxicity Dose-response Data in a Human Risk Context
Marc Beal, Health Canada, Ottawa, Canada

4:00 PM- 4:30 PM
Conclusions and Closing remarks
Andreas Zeller & Paul White


Workshop 03
12:00 PM - 5:00 PM |
Leveraging the CometChip & the MicroColonyChip for studies of DNA Damage/Repair and Cell Growth
Chair: Bevin Engelward, Co-Chair: Les Recio, Young Investigator:
Mojave Learning Center Room(Registration addon required)

The comet assay is now a broadly accepted approach for measuring a variety of DNA lesions, including base adducts, strand breaks and crosslinks. The assay has utility in epidemiology, drug development, and chemical safety, and yet the traditional assay is slow, laborious and prone to bias. The CometChip was developed as a higher throughput version of the comet assay. This platform exploits cell microarray technology that prevents bias caused by comet selection, is compatible with a standard 96 well microtiter plate, and allows for rapid and automated imaging and analysis. By improving throughput by orders of magnitude, the assay enables studies that were previously impractical due to difficulties in sample handling and laboriousness. Variations on the CometChip offer additional utility by making it possible to detect bulky lesions that require metabolic activation and by enabling analysis of hepatocyte spheroids. This workshop will include research updates that demonstrate its utility, detailed guidance on performing the assay and a hands-on demonstration. In addition to the CometChip, this workshop also provides the opportunity to learn about the MicroColonyChip platform, another cell microarray platform that is a high-throughput version of the traditional Colony Forming Assay.


Special Event
5:00 PM - 6:30 PM |
EMGS President's Welcome Reception and Student & New Investigator Poster Session
Pasadena/Sierra/Venura Room


Keynote 01
6:30 PM - 7:30 PM |
TBD
Mary-Claire King, PhD, Professor of Genome Sciences and Medicine, University of Washington
Catalina/Madera Room


 

Sunday, September 13, 2020

7:00 AM - 5:00 PM | Registration
Ballroom Foyer Room

7:00 AM - 5:00 PM | Speaker Ready Room
Cactus Room


Special Interest Groups

7:00 AM - 8:15 AM |
Epigenomics SIG
San Jancinto Room

7:00 AM - 8:15 AM | In Vivo Mutagenesis SIG
Santa Rosa Room

7:00 AM - 8:15 AM | Applied Genetic Toxicology SIG
Andreas Room


Symposium 01
8:30 AM - 10:30 AM |
To the Stars and Back Again- Studies in Space Radiation Research
Chair: Janice Pluth, Co-Chair: Susan Bailey, Young Investigator: TBD
Mojave Learning Center Room

The recently reported findings from NASA’s Twin Study and first One Year Mission brought much attention to the exciting research being done to better understand human health effects of long duration space flight. Certainly, induction of DNA damage and genomic instability are of concern, however little is known in regard to such responses resulting from chronic exposure to space radiations and the space environment.

Telomeres in Space
Susan M. Bailey, Colorado State University

Defining Immune-Metabolic- and Protein Production-Related Stresses from by Space Capsule Launch, Zero Gravity and Re-entry to Earth
Michael Snyder, Ph.D., Stanford University

The Landscape of DNA and RNA Methylation Before, During, and After Human Space Travel
Christopher E. Mason, Ph.D, Weill Cornell Medicine, Department of Physiology and Biophysics


Symposium 02
8:30 AM - 10:30 AM |
Modernizing the Genotoxicity Testing Paradigm: How Adverse Outcome Pathways, Integrated Approaches to Testing and Assessment (IATA), and Quantitative Analyses in Genetic Toxicology are Impacting Modern Risk Assessment Practices
Chair: Alexandra Long, Co-Chair: Stefan Pfuhler, Young Investigator: Eunnara Cho
Catalina Room

The genotoxicity testing paradigm is transitioning from in vivo testing towards predictive in vitro and in silico methods, and quantitative genetic toxicology applications. AOPs provide a framework for documenting the biological knowledge and empirical data to describe the key events leading to adverse outcomes. Quantitative modeling is required to understand the relationship between key events and build predictive toxicology models from AOPs, and identify points of departure. AOPs can be leveraged to build test paradigms that implement the newest (non-test guideline) test methods for regulatory decision-making. One approach to efficiently increase application of these novel concepts in risk assessment is through the development of Integrated Approaches to Testing and Assessment (IATA).

This symposium will provide: 1) an introduction to AOPs and IATAs, recent advances in these programs, and examples of how they are impacting risk assessment practices; 2) a synthesis of the AOP projects ongoing within the Health and Environmental Sciences Institute’s (HESI) Genetic Toxicology Technical Committee (GTTC) and their expected applications; 3) advances in the use of genetic toxicity dose-response data including discussions on critical effects sizes and uncertainty factors applied to points of departure; 4) application of the IATA concept in integrated genotoxicity testing by Health Canada in their GeneTox21 program; 5) the use of AOPs in the development of predictive toxicology models. Collectively, this symposium will provide an overview of different collaborative efforts to modernize genotoxicity assessment through the use of AOPs, IATA and genotoxicity dose-response analysis.

AOPs and IATA: What They Are and Why They Should Matter to the EMGS
Jason O'Brien, Environment and Climate Change Canada

The Health and Environmental Institutes Genetic Toxicology Technical Committee AOP initiative: The Growing Genotoxicity AOP Network and Practical Applications
Stefan Pfuhler, Procter & Gamble

Risk Assessment and Regulatory Decision Making Based on Mutagenicity Dose-response Data - Case Studies of Noteworthy Environmental Mutagens
George Johnson, Swansea University

Harnessing Genomics and AOPs for Predictive Toxicology
Edward Perkins, US Army Corps of Engineers

GeneTox21 IATA: Leveraging AOPs and Quantitative Dose-response Modeling to Modernize Genotoxicity Assessment
Julie Cox, Health Canada


Symposium 03
8:30 AM - 10:30 AM |
The Toxicology of E-Cigarettes
Co-Chairs: Catherine Gibbons, Dan Roberts
Young Investigator: Esther Omaiye
Madera Room

The widespread use of e-cigarettes, particularly among young people, and growing public health concerns are accompanied by an increasingly discordant message regarding the evidence of toxicity presented by academia and industry. A discussion of the existing toxicity and genotoxicity data, and recommendations for future testing needs, will help clarify actual risk and help inform regulatory decision-making. Speakers will present current evidence of the toxic and genotoxic effects of e-cigarettes; the end of the session will provide time for an open and objective facilitated discussion on what is known regarding the toxicity of e-cigarettes.

Toxicology of e-cigarettes
Ilona Jaspers, University of North Carolina at Chapel Hill

Chemical Elements and Metals in Aerosols from Three Generations of Electronic Cigarettes: Do They Cause EVALI?
Monique Williams, University of California, Riverside

In Vitro Genotoxicity Testing of e-Cigarette Formulations and Technical Issues Involved
Leon Stankowski, Charles River Laboratories

Toxicology of e-cigarettes (Title TBD)
Daniel Smart, Philip Morris International

E-cigarettes: The FDA perspective
Priscilla Callahan-Lyon, US FDA, Center for Tobacco Products

Panel Discussion
To be led by Les Recio, ILS, Inc


10:30 AM - 11:00 AM | Coffee Break
Pasadena/Sierra/Venura Room


Keynote 02
11:00 AM - 12:00 PM |
A Compendium of Mutational Signatures of Environmental Agents in Human Cancers and Normal Cells
Serena Nik-Zainal, CRUK Advanced Clinician Scientist and Honorary Consultant in Clinical Genetics, University of Cambridge

Catalina/Madera Room


12:00 PM - 1:30 PM | EMM Editorial Board
Chino Room


Special Event
12:00 PM - 1:30 PM |
Student and New investigator Luncheon
All Students and New Investigators are invited
Pueblo Room


Symposium 04
1:30 PM - 3:30 PM |
Nucleosome Dynamics and Environmental Stress
Chair: Kara Bernstein, Co-Chair: TBD, Young Investigator: Heather O’Hagan
Catalina Room

Our cells are constantly responding the onslaught of environmental toxicants that threaten the integrity of our genome. This symposium entitled “Nucleosome Dynamics and Environmental Stress” will address current topics of how our environmental exposures influence nucleosome dynamics leading to different repair outcomes. We will cover different types of DNA damage and how individual DNA repair pathways are engaged to ensure genomic integrity focusing on oxidative damage, mismatch repair, and chromatin remodeling complexes.

Mismatch Epair, Oxidative Damage, and Epigenetic Alteration in Cancer
Heather O’Hagan, Indiana University School of Medicine

Chromatin Remodeling: INO80 Complex
Ashby Morrison, PhD, Stanford University

Oxidative Damage and Environmentally Induced DNA Damage
Sarah Delaney, PhD, Brown University

Panel Discussion


Symposium 05
1:30 PM - 3:30 PM |
Mitochondria: Environment, Epigenetics, and Disease
Chair: Aishwarya Prakash, Co-Chair: TBD, Young Investigator: Laurie H. Andolina
Madera Room

Over the past few decades mitochondria have emerged as more than just the powerhouse of the cell. Mitochondrial DNA, like its nuclear counterpart is damaged by both environmental and endogenous agents. Aberrant mitochondrial DNA metabolism leads to a myriad of diseases including aging related neurological disorders. This symposium entitled “Mitochondria: Environment, Epigenetics, and Disease” will address current topics of how onslaught to mtDNA influences epigenetic changes and mitochondrial disease.

Mitochondrial DNA Stress Signaling
Gerald S. Shadel, Salk Institute for Biological Studies

Ultrasensitive Deletion Detection Links Mitochondrial Replication, Disease and Aging
Bill Copeland, National Institute of Environmental Health Sciences

Genomic Effects of Mitochondrial Dysfunction
Janine Santos, National Institute of Environmental Health Sciences


Symposium 06
1:30 PM - 3:30 PM |
Personalized Cancer Risk and Prevention: Are We Ready?
Chair: Rosalie Elespuru, Co-Chair: TBD, Young Investigator: TBD
Mojave Learning Center Room

It has been known for some time that both genes and environment are factors in human cancer development. In the era of personal genomics, what is the likelihood that we can begin to assess personalized cancer risk, instead of overall cancer risk? A default cancer risk assessment as practiced today includes “uncertainty factors” to account for differential susceptibility, sensitivity, and other unknowns and variables within the human population. Assessment of cancer risk in general is a common goal, but there is information currently available to address cancer risk for specific cancers. Cancers for which genetic, environmental, viral and other associations are well established and could be used in personalized cancer risk assessments include colon, liver, head and neck, and lung cancer. This symposium includes a general overview of the potential for personalized cancer risk and presentations exploring the chemical, genetic, epigenetic, viral, dietary, exercise, and other environmental factors known for specific involvement in the development of colon, liver, and other cancers in humans.

Evolution of Cancer Risk Assessment from Percival Pott to Personalized Cancer Prevention
Rosalie Elespuru, US Food and Drug Agency

Genetic and Nutritional Contributions to Colon Cancer
TBA

Preventable Factors in Liver Cancer
Farhad Islami, Cancer Surveillance Research, American Cancer Society

Panel Discussion: Future Approaches to Personalized Cancer Prevention


4:00 PM - 4:30 PM | Coffee Break
Pasadena/Sierra/Venura Room


4:30 PM - 6:30 PM | Poster Session #1
Light Refreshments provided
Pasadena/Sierra/Venura Room


Special Event
6:30 PM - 8:30 PM |
Meet and Greet Mixer
Light Refreshments provided
Poolside Room


 

Monday, September 14, 2020

7:00 AM - 5:00 PM | Registration
Ballroom Foyer Room

7:00 AM - 5:00 PM | Speaker Ready Room
Cactus Room


Special Interest Groups

7:00 AM - 8:15 AM |
DNA Repair & Mutagenic Mechanisms SIG
Andreas Room

7:00 AM - 8:15 AM | Genotoxity Risk Assessment and Public Health (GRAPH) SIG
San Jancinto Room

7:00 AM - 8:15 AM | The Genomics and Data Sciences SIG
Santa Rosa Room


Symposium 07
8:30 AM - 10:30 AM |
Inflammation and Genomic Instability
Chair: Joann Sweasy, Co-Chair: TBD, Young Investigator: TBD
Mojave Learning Center Room

Recent findings have emerged that suggest an interplay between genomic instability and inflammation. Genomic instability drives inflammation but inflammation is also suspected to induce genomic instability that leads to cancer. The presentations in this symposium by leading experts in the field will present cutting edge research findings that explore the complex relationships between genomic instability and inflammation.

cGas Sting and The Inflammatory Response
Zhijian Chen, UT Southwestern

Genomic Instability and Inflammation
John Schimenti, Cornell University

Immunogenicity of BRCA Mutant Cancers
Katherine Nathanson, University of Pennsylvania


Symposium 08
8:30 AM - 10:30 AM |
Application of Computational Approaches and Machine Learning to Risk Assessment and Genetic Toxicology
Chair: Jeffrey C. Bemis, Co-Chair: TBD, Young Investigator: TBD
Catalina Room

Summary: The application of computational toxicology to product safety testing is increasing at a vary fast pace. Based on the opportunities that these new methodologies are providing for data visualization and interpretation, the EMGS membership will benefit from learning about these approaches now so they can prepare for the eventual adoption that is likely inevitable.

This session serves as a complement to the EMGS Bioinformatics Challenge that will be occurring at the meeting in Palm Springs. Those that are already working in this area will gain additional knowledge from the peer’s case examples and those new to the field will get an introduction to data science and how it is being used.

Application of New Approach Methodologies (NAMs) to Chemical Risk Assessment
Maureen Gwinn, Division Director, Biomolecular and Computational Toxicology Division, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency

Trends and Application of Computational Toxicology Approaches
Agnes Karmaus, Senior Staff Toxicologist at Integrated Laboratory Systems, In

Predicting Genotoxic Classification through Robust Concentration-Response Modeling and Machine Learning on Screening End-Points
Elias Ozolior, Computational Toxicology in Global Pathology and Investigative Tox, Pfizer, Inc.


Symposium 09
8:30 AM - 10:30 AM |
Genomic Alterations and Environmental Factors Involved in Neurodevelopmental/Neuropsychiatric Disorders
Chair: Christi Walter, Co-Chair: Noboru Hiroi, Young Investigator: TBD
Madera Room

A variety of genome alterations are associated with neuropsychiatric disorders ranging from point mutations, to epigenetic changes, trinucleotide repeat expansions, and CNVs. Environmental factors, such as pesticides and air pollution, and maternal physiological conditions such as diabetes and immune disorders, are also associated with neuropsychiatric/neurodevelopmental disorders. De novo mutations related to the paternal age effect are linked with many of these diseases, such as autism spectrum disorders. This symposium will cover various genomic alterations and environmental factors that appear to impose on many neuropsychiatric/neurodevelopmental disorders and that impinge on environmental mutagenesis and genomics.

Dimensional Deconstruction of Neuropsychiatric Disorders associated with 22q11.2 Copy Number Variation
Noboru Hiroi, UT Health San Antonio

Oxidative Damage and its Role in Genetic Instability at Triplet Repeats
Cynthia McMurray, Lawrence Berkeley Laboratories

Paternal Age-Related Germline Mutagenesis in the Etiology of Neurodevelopmental Disorders
Christi Walter, UT Health San Antonio


Keynote 03
11:00 AM - 12:00 PM |
TBD
Kári Stefánsson, M.D., Dr Med, deCDE Genetics, Iceland
Catalina/Madera Room


Special Event
12:00 PM - 1:30 PM |
Women in EMGS Luncheon
Pueblo Room


Platform Sessions
1:30 PM - 3:30 PM |
Platform Session # 1
Mojave Learning Center Room

1:30 PM - 3:30 PM | Platform Session # 2
Catalina Room

1:30 PM - 3:30 PM | Platform Session # 3
Madera Room


Young Scientist Award
3:45 PM - 4:45 PM |
TBD
Catalina/Madera Room


Poster Viewing
4:45 PM - 6:45 PM |
Poster Session #2
Pasadena/Sierra/Venura Room


Special Event
6:45 PM - 9:00 PM |
Social Event at La Quinta Brewing Co. - Palm Springs Taproom
Sign up required


 

Tuesday, September 15, 2020

7:00 AM - 5:00 PM | Registration
Ballroom Foyer Room

7:00 AM - 5:00 PM | Speaker Ready Room
Cactus Room

Special Interest Group
7:00 AM - 8:15 AM |
Germ Cell and Heritable Effects SIG
Andreas Room

Committee Meetings
7:00 AM - 8:15 AM |
Hollaender Outreach
Santa Rosa Room

7:00 AM - 8:15 AM | Publication Policy
San Jancinto Room


Symposium 10
8:30 AM - 10:30 AM |
Non coding RNA: Shedding Light on the Dark Matter of the Genome
Chair: Isabelle Miousse, Co-Chair: TBD, Young Investigator: Sumira Phatak
Mojave Learning Center Room

Although less than 1.5% of the human genome codes for proteins, as much as 80% is transcribed. Haphazardly deemed junk DNA for decades, we now refer to these resulting transcripts as non-coding RNA (ncRNA) and know that they serve a number of essential regulatory functions. Circular RNA (circRNA), long non-coding RNA (lncRNA), and microRNA (miRNA) are examples of ncRNA species involved with maintenance of homeostasis, and their roles in environmentally-induced disease are only starting to be discovered. Circular RNA (circRNA) are more abundant in most cells than mRNA and serve as miRNA sponges, transcription factors, and alternative splicing guides, functions that ultimately regulate gene expression. These circRNA are aberrantly expressed in a number of cancers, including colorectal cancer, and may be developed to serve as diagnostic or therapeutic tools in the future. Long non-coding RNA (lncRNA) make up the majority of the non-coding transcriptome in humans, with more than 30,000 identified to date. Although most lncRNA are yet to be characterized, this diverse group of molecules is well known to regulate gene transcription, post-transcriptional modifications, and epigenetic regulation. Evidence suggests that both imprinting and X-chromosome inactivation are lncRNA directed processes. Dysregulation of several lncRNAs has been identified in neurological diseases and cancers. MicroRNA have been shown to be responsive to various environmental factors including methyl-deficient diet, bioactive food molecules, and toxicants such as heavy metals. miRNA may play an important role in pathogenesis of cancers, appearing to function as tumor suppressors or oncogenes. Ultimately, miRNA may even serve as a cancer diagnostic biomarker or therapeutic tool for prevention and treatment. This symposium will discuss the latest discoveries on function of circRNA, lncRNA, and miRNA, with an emphasis on their potential roles as mechanisms of disease pathogenesis and toxicity.

The Intersection of Neurotoxicants, MicroRNAs and Disease
Walter Lukiw, Louisiana State University

The Cell is a Bag of RNA: Revelations from Dingle Cell RNA Analysis
Alina Isacova, Stanford University

Are Long Intergenic non-coding RNAs Drivers of Cancer?
Ahmad Khalil, Case Western Reserve University School of Medicine

Emerging Role of Long non-coding RNAs in Cancer Precision Medicine
Stephanie Huang, University of Minnesota


Symposium 11
8:30 AM - 10:30 AM |
Advancements in Mutagenicity Assessment
Chairs: Dan Roberts, Charles River and Bob Young. Young Investigator: TBD
Catalina Room

Current genetic toxicity testing strategies identify mutagenic properties of novel products via phenotypic changes in a variety of in vitro and in vivo test systems. For example, the gold standard for detecting mutagenesis in vitro is the bacterial reverse mutation assay that uses highly engineered strains of Salmonella and E.coli to detect restoration of essential amino acid synthesis via reversion to wild-type. The biological relevance of in vitro mutagenic events can be further explored in vivo using transgenic rodent models, where phenotypic change in target/reporter genes is used to assess tissue-specific mutagenesis. To date, assessment of mutagenesis has mostly been limited to indirect measurements of phenotypic change due to mutation of reporter genes. For the first time, transformative new sequencing technologies and bioinformatics permit direct measurement of a variety of endpoints including mutant frequency and mutant spectrum directly in genomic DNA. This session aims to explore how these new technologies can be applied to these existing nonclinical assays and new applications as well as how these nonclinical applications translate to human cancer risk.

Determining Mutational Spectra from Existing Genetox Assays: Ames Test
Shoji Matsumura, Kao Corporation

Is Duplex Sequencing Equivalent to the Plaque Assay for Detecting cII Mutants in Big Blue® Rodents
Bob Young, Millipore-Sigma

Germ Cell Mutagenesis Update to Support OECD TG 488
Francesco Marchetti, Health Canada

Error-Corrected Duplex Sequencing; Bioinformatic Challenges
Clint Valentine, TwinStrand

Risks and Challenges of Utilizing Deep Sequencing for Hazard Identification
Jan Vijg, Einstein College of Medicine


Symposium 12
8:30 AM - 10:30 AM |
New Discoveries on the Role of the Epigenome in the Relationship between the Environment and Human Health.
Chair: Nina Holland, Co-Chair: Bambarendage Pinithi Perera
Madera Room

(Revised) Links between environmental exposures, diet and human health receive increasing attention. Accumulating evidence indicates that associations between environmental exposures and disease can be driven by changes in the epigenome. For example, many environmental factors have been linked to cancer, with much of the research focused on mutations in cancer genomes. However, widespread epigenetic changes have also been reported for many cancers. This symposium will provide links between specific exposures and epigenetic and other molecular changes in disease processes. The goals of this session are to present novel mechanistic relationships between environmental exposures, epigenomics and disease processes, as well as the possibility of manipulating the epigenome to reduce disease risk.

Cancer Chemoprevention Via Dietary Targeting of Epigenetic Pathways
Emily Ho, College of Public Health and Human Sciences, Oregon State University

Perinatal Exposure, Epigenomics and Disease Susceptibility: The PON1 Story
Karen Huen, University of California Berkeley

Epigenetic Changes in Cardiovascular Disease
Thomas Vondriska, Departments of Anesthesiology, Medicine, and Physiology, David Geffen School of Medicine, UCLA


10:30 AM - 11:00 AM | Coffee Break
Pasadena/Sierra/Venura Room


Keynote 04
11:00 AM - 12:00 PM |
The Enigma of Viral Noncoding RNAs
Joan A. Steitz, PhD, Sterling Professor of Molecular Biophysics and Biochemistry, Yale School of Medicine
Catalina/Madera Room

Committee Meetings
12:00 PM - 1:30 PM |
Awards and Honors
Andreas Room

12:00 PM - 1:30 PM | Endowment Board
San Jancinto Room

12:00 PM - 1:30 PM | Special Interest Group Leaders
Santa Rosa Room


Platform Sessions
1:30 PM - 3:30 PM |
Platform Session # 4
Mojave Learning Center Room

1:30 PM - 3:30 PM | Platform Session # 5
Catalina Room

1:30 PM - 3:30 PM | Platform Session # 6
Madera Room


Hollaender Award
3:45 PM - 4:45 PM |
TBD
Paul A. White, Ph.D., Environmental Health Science and Research Bureau, Mechanistic Studies Division
Catalina/Madera Room


4:45 PM - 6:00 PM | EMGS Business Meeting
All EMGS Members and interested EMGS Members are encouraged to attend.
Mojave Learning Center Room


Committee Meetings
6:00 PM - 7:00 PM |
Finance and Fundraising
San Jancinto Room

6:00 PM - 7:00 PM | Membership Professional Development
Andreas Room

6:00 PM - 7:00 PM | Public Relations and Communications
Santa Rosa Room


Special Event
7:00 PM - 11:00 PM |
EMGS Awards Banquet
Enjoy Dinner and help us recognize our award winners. Open Dance Floor follows the banquet.
Catalina/Madera Room


 

Wednesday, September 16, 2020

7:00 AM - 5:00 PM | Registration
Ballroom Foyer Room

8:00 AM - 12:00 PM | Speaker Ready Room
Cactus Room

 

Symposium 13
8:30 AM - 10:30 AM |
The Landscape of Human Germline Mutation
Chair: Jonatan Axelsson, Co-Chair: Carole Yauk, Young Investigator: Mathia Colwell
Mojave Learning Center Room

With increasing amounts of information emerging from global genome sequencing analyses we’re beginning to more deeply understand the processes, landscape and impacts of de novo mutations mediated through the male and female germline. In this session we will hear about the most recent discoveries about the role of de novo mutations as a cause of diseases such as intellectual disability and male infertility, including the impact of non-coding mutations. Speakers will present their findings on baseline rates of de novo mutations, how mutation rates differ between populations and families, and how methylation can influence mutation locations. Finally, we will hear about work exploring the contributions of "gonosomal", "post-primordial germ cell specification" and "single gamete" mutations to overall mutation burden and impact on the next generation.

Causes and Consequences of de novo Mutations in Health and Disease
Joris Veltman, Newcastle University, UK

Large, Three-Generation CEPH Families Reveal Post-Zygotic Mosaicism and Variability in Germline Mutation Accumulation
Aaron Quinlan, University of Utah

Timing, Rates and Spectra of Human Germline Mutation
Sarah Lindsay, Wellcome Sanger Institute


Symposium 14
8:30 AM - 10:30 AM |
Dynamic RNA Modifications: Roles in Environmental Response and Disease
Chair: Daniel Shaughnessy, Co-Chair: Frederick L. Tyson, Young Investigator: Jaclyn Goodrich
Catalina Room

Dynamic RNA modifications can interpret environmental challenges and respond by altering gene regulation, biological pathways and disease outcomes. Emerging evidence suggests that chemical modifications to RNA have critical roles in basic biological processes including embryonic stem cell differentiation, excitotoxic cell death, development, intergenerational inheritance of acquired traits, regulation of RNA stability, temperature adaptation, meiotic progression, alternative splicing, gene expression and regulation of RNA-RNA and RNA-protein binding interactions. The impact of the environment on chemical modifications of RNA molecules (the epitranscriptome) in the development of adverse human health outcomes is relatively unexplored. Technology advances in recent years have accelerated the detection of RNA modifications, and the RNA Modification Database currently lists approximately 100 RNA modifications identified in eukaryotic cells. This database also reveals transfer and ribosomal RNA are heavily modified, and many of these same modifications occur in messenger RNA and non-coding RNAs. The function of most of these modifications remains a mystery, despite their potential to influence RNA properties and functions and interactions with other molecules. This session will bring together leading investigators in the emerging area of functional RNA modifications to discuss the state of the science including how environmental exposures impact this layer of cellular regulation.

A Novel Gene Regulatory Mechanism in Mammalian Cells: Crosstalk between m6A mRNA Modification and Histone Modifications
Crystal Zhao, Sanford Burnham Prebys Medical Discovery Institute

Oxidative Stress and RNA Methylation
Ricardo C. Aguiar, University of Texas Health Science Center San Antonio

Translational Regulation during Cigarette Smoking-Induced Reprogramming of the tRNA Epitranscriptome
Thomas J. Begley, The State University of New York at Albany


Symposium 15
8:30 AM - 10:30 AM |
Alternative DNA Structures: Naturally-occurring Impediments to Transcription and Replication, and Sources of Genomic Instability
Chair: Karen Vasquez, Co-Chair: Kristin Eckert, Young Investigator: Guliang Wang
Madera Room

Repetitive sequences are abundant in the human genome, and have the capacity to adopt alternative (i.e. non-B) DNA structures. More than a dozen non-B DNA structures have been characterized to date, e.g., Z-DNA, H-DNA, G4-DNA, hairpins, and cruciforms. These alternative DNA structure-forming sequences have been found to impact DNA metabolic processes, as they can act as impediments to DNA and RNA polymerases, helicases, DNA repair enzymes, etc. Moreover, these structure-forming sequences have been identified as a naturally occurring source of genetic instability, and have been implicated in disease etiology and evolution. For example, non-B DNA-forming sequences have been found to be substantially enriched at translocation breakpoints in human cancer genomes. Because certain sequence elements are required for the formation of a particular non-B DNA structure (e.g. inverted repeats can adopt cruciform structures, alternating purine-pyrimidine dinucleotide repeats can adopt Z-DNA structures, etc.), algorithms have been designed to search databases for potential non-B DNA-forming sequences. Such information can inform on their potential roles in modulating transcription, replication, repair, and disease etiology. In this session, a new technology for genome-wide mapping of non-B DNA structures will be presented. In addition, their roles in disease etiology, and the mechanisms involved in their error-generating and error-free processing will be discussed.

Alternative DNA Structures and Genomic Instability
Catherine Freudenreich, Tufts University

Genome-Wide Mapping non-B DNA Sequences
David Levens, National Institute of Environmental Health Sciences

R loops and Genomic Instability
Andres Aguilera, Universidad de Sevilla


10:30 AM - 11:00 AM | Coffee Break
Pasadena/Sierra/Venura Room


EMGS Award
11:00 AM - 12:00 PM |
Precision Medicine of Cancer: Environment, Molecular Epidemiology and p53
Curtis Harris, MD, NIH, NCI, CCR
Catalina/Madera Room


Committee Meetings
12:00 PM - 1:30 PM |
2021 Program Committee
Andreas Room


Platform Sessions
1:30 PM - 3:30 PM |
Platform Session # 7
Mojave Learning Center Room

1:30 PM - 3:30 PM | Platform Session # 8
Catalina Room

1:30 PM - 3:30 PM | Platform Session # 9
Madera Room


3:00 PM - 6:00 PM | EMGS Council Meeting
Andreas Room

 

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Download PDF of the EMGS 2020 Program Overview