Event Agenda

Grow your knowledge with in-depth sessions in research modalities such as traditional and
non-traditional animal models, novel
in vitro and ex vivo approaches to disease modeling, the application of technologies such as CRISPR/Cas9 gene editing, 3D bioprinting, the exploitation
of the microbiome and co-opting the immune system in the treatment of disease.

  • Tuesday, September 26                                                                +

    8:30 a.m.

    Conference Welcome & Live Broadcast Start

    James C. Foster

    President, Chairman, CEO, Charles River

    8:40 a.m.

    Charles River Annual Research Models in Drug Discovery Award Presentation

    Prion Alliance/Broad Institute


    9:00 a.m.

    Historical Perspective on Reverse Translational Medicine

    Elazar Edelman, MD, PhD

    Thomas D. and Virginia W. Cabot Professor of Health Sciences and Technology, Massachusetts Institute of Technology; Professor of Medicine, Harvard Medical School; Senior Attending Physician, Coronary Care Unit, Brigham and Women’s Hospital

    10:00 - 10:20 a.m.     Break

    10:20 a.m.

    Understanding Complex Interactions in Metabolic and Cardiovascular Disease:
    Genetics, the Microbiome, Sex, and Diet

    Jake Lusis, PhD

    Professor of Microbiology, Human Genetics and Medicine, University of California, Los Angeles


    One important application of animal models is, of course, to identify mechanisms through experimental perturbation. A less well-known application is to utilize natural variation to study complex interactions. The lab detailed in this presentation studies a panel of diverse inbred strains of mice to understand interactions between genetics, sex, the microbiome, and diet in the context of cardiometabolic disease.


    One surprising research finding is that genetic variation of the host is a major determinant of the composition of the gut microbiome. For example, when a panel of common inbred strains of mice was maintained in the same vivarium and fed the same diet, the heritability of gut microbiota was about 40% or higher for most genera of gut bacteria. Nevertheless, the microbiome could be dramatically altered by dietary challenge, and microbiota transplantation studies showed that the effects of the diets on the host were dependent in part upon genetic background, sex, and microbiome composition. While the lessons gleaned from studies in mice may not be directly translatable to humans, an understanding of the basic principles will help guide human studies.

    11:20 a.m.

    Bench to Bedside in Oncology: Translation of Cancer Vaccines from Mouse Models
    to Human Clinical Trials

    Jay Berzofsky, MD, PhD

    Chief, Vaccine Branch; Senior Investigator Head, Molecular Immunogenetics and Vaccine Research Section, National Cancer Center, NIH


    This presentation will review two cancer vaccine platforms developed in transgenic mouse models that were successfully translated to human trials with promising results. The first was developed by studying TARP, a prostate cancer antigen discovered at NCI, mapping HLA-A2-presented epitopes, and testing these in HLA-A2 transgenic mice. Additional studies in mouse models were conducted following amino acid modification to improve binding to HLA-A2 – a process referred to as ““epitope enhancement.” The mouse studies led to a phase I clinical trial in patients with stage D0 prostate cancer, in which the primary tumor is removed but a rising PSA indicates microscopic recurrence, before any tumor can be seen radiographically.


    The second platform is a recently developed vaccine targeting the HER2 oncogene, responsible for about one-quarter of breast cancers and a smaller percent of several other cancers. For mice, an adenovirus expressing the extracellular and transmembrane domains of rodent HER2 was developed. Positive effects in HER2-transgenic BALB/c mice and wild-type BALB/c mice has led to an in-progress clinical trial in patients with advanced metastatic HER2+ tumors who have failed other therapies.

    12:20 - 1:30 p.m.        Lunch

    1:30 p.m.                     AFTERNOON BREAKOUT SESSIONS (see schedule)

    4:50 p.m.                     Closing Remarks; Live Broadcast Ends

    5:30 p.m.                     Reception

    Tuesday Track 1
    Approaches for Rare and Neglected Diseases

    1:30 p.m.

    Stem Cell Approaches for Studying Inherited Cardiovascular Diseases

    Joseph C. Wu, MD, PhD

    Professor & Director, Stanford Cardiovascular Institute; Simon H. Stertzer, MD Professor of Medicine & Radiology


    2:30 p.m.

    Team Science to Advance Therapeutics for Batten Disease

    David Pearce, PhD

    President of Research, Sanford Health; Pediatrics Professor, Sanford School of Medicine, University of South Dakota


    The fatal, primarily childhood, neurodegenerative disorders known collectively as neuronal ceroid lipofuscinoses (NCLs) are currently associated with mutations in 14 genes. The protein products of these genes (CLN1 to CLN14) differ in their function and their intracellular localization. NCL-associated proteins have been localized mostly to lysosomes (CLN1, CLN2, CLN3, CLN5, CLN7, CLN10, CLN12, and CLN13) but also the endoplasmic reticulum (CLN6 and CLN8), or in the cytosol associated to vesicular membranes (CLN4 and CLN14). Some of them, such as CLN1 (palmitoyl-protein thioesterase 1), CLN2 (tripeptidyl-peptidase 1), CLN5, CLN10 (cathepsin D), and CLN13 (cathepsin F), are soluble lysosomal proteins; others, like CLN3, CLN7, and CLN12, have been proposed to be lysosomal transmembrane proteins.


    This presentation will examine mouse models and recently developed porcine models for many of these NCLs that have facilitated therapeutic studies leading to clinical trials. As our understanding of the pathology of these diseases advances, identifying the right collaborators to execute understanding disease mechanisms, performing preclinical studies, and moving to clinical trials will be critical.

    3:30 - 3:50 p.m.           Break

    3:50 p.m.

    How the Genomics Revolution is Changing Understanding of Rare Diseases and Cancer

    C. Jimmy Lin, MD, PhD, MHS

    Founder/CEO, Rare Genomics Institute; CSO, Oncology, Natera
    Will not be recorded

    Tuesday Track 2
    Practical Applications of Bedside to Bench Reverse Translation

    1:30 p.m.

    The Translational Medicine Guide: “Asking the Right Question at the Right Time"

    Laetitia Devy-Dimanche, PhD

    Head of Global Project Management, EMD Serono, Inc.


    EMD Serono’s Translational Medicine Guide (TxM guide) has been developed to help each project team maximize success in achieving clinical proof of concept (cPoC) by considering multiple aspects of drug discovery and development. The TxM guide is a forward-looking strategic planning framework for teams to ask “the right questions at the right time.”


    This presentation will lay out the three primary goals of the TxM guide: (1) to identify the right biological target for the selected disease, (2) to identify the right molecule that delivers the right exposure at the target site of action and elicits the desired target modulation over the stated time period, without compromising patient safety, and (3) is to identify the right patient group in the selected disease. The speaker will then outline how the TxM guide helps teams to build a body of scientific and medical evidence to be better positioned to achieve positive cPoC.

    2:30 p.m.

    Neurimmune’s Reverse Translational Medicine Platform: Development of Human Antibodies
    for the Treatment of Protein Aggregation Diseases

    Jan Grimm, PhD

    Chief Scientific Officer, Neurimmune Holding AG

    Will not be streaming live


    Abnormal folding and aggregation of endogenous proteins in the brain or peripheral tissues characterizes many degenerative diseases, including Alzheimer’s and Parkinson’s disease, amyotrophic lateral sclerosis, and type 2 diabetes. The abnormal protein aggregates are stable; they can be involved in cell-to-cell propagation of pathology and can adopt conformations with cytotoxic activities. The presence of plasma antibodies against such misfolded proteins suggests active humoral immune responses, along with the formation of B cell memory.


    In this presentation, the speakers will detail their the hypothesis that selected B cell clones triggered by neoepitopes of pathological protein conformations encode antibodies that can block the toxicity and promote the clearance of protein aggregates. To test this hypothesis, the memory B cell repertoires of a large cohort of healthy aged human donors were analyzed, including donors with disease risk and abnormally slow progression or onset. Based on these analyses, the research team generated recombinant high-affinity human monoclonal antibodies that can be effective in neutralizing toxicity, blocking cell-to-cell propagation, and triggering the removal of protein aggregates by microglia or macrophage-mediated phagocytosis. Recent study results will be reviewed.

    3:30 - 3:50 p.m.           Break

    3:50 p.m.
    Improving Translational Animal Models of CNS Disease – The Critical Role of New Technologies

    Antti Nurmi, PhD

    Managing Director, Charles River


    This presentation will offer an overview of established animal models of CNS diseases, their key properties, and how well they model human disease. Issues related to interpretations in animal behavior studies will be addressed, along with how valid interpretations mimic human symptoms and behaviors. The speakers will also explore novel methods that help build translational bridges between mice and men, in turn, improving confidence in the preclinical data to increase translatability to the clinic. These examples include clinically applied imaging techniques, such as positron emission tomography (PET), magnetic resonance imaging (MRI), as well as more advanced animal behavioral techniques such as touch screen operant assays and kinematic motion analysis. Attendees will also learn how multi-model studies in the rodent brain led to the discovery of vascular and metabolic anomalies of the liver, which has serious implications for biomedical research beyond CNS disease research.

    Tuesday Track 3

    Novel In Vitro Models for Drug Discovery - Technologies and Trends


    1:30 p.m.

    Patient in a Dish – Non-alcoholic Steatohepatitis (NASH) and Beyond

    Ryan Feaver, PhD

    Program Leader, NASH at HemoShear Therapeutics, LLC


    Non-alcoholic fatty liver disease (NAFLD) is a rapidly emerging public health crisis, affecting up to one-third of the US population, and can progress to non-alcoholic steatohepatitis (NASH) and cirrhosis, often resulting in liver transplant or death. This is one of the most active areas in drug discovery with over 40 drugs in the preclinical and clinical phase of development, but none to date have advanced beyond phase III clinical trials or been approved for therapy. The field is hampered by a lack of disease understanding and overreliance on >40 rodent models unable to map to the human response.


    This presentation introduces an in vitro approach that combines primary human hepatocytes, stellate cells, macrophages, a physiologically relevant tissue microenvironment consisting of liver sinusoid hemodynamic and transport conditions, and clinically-derived concentrations of NASH risk factors to create “NASH in a dish.” To date, the in vitro human NASH model has been used to survey the current drug development landscape in order to understand the therapeutic gaps, providing the principal data set to identity new targets for NASH therapies. Future research applications will also be discussed.

    2:30 p.m.
    Metastatic Breast Cancer Explored in a Human, 3D, Microfluidic Liver Chip

    D. Lansing Taylor, PhD

    Director, University of Pittsburgh Drug Discovery Institute, Allegheny Foundation; Professor of Computational and Systems Biology, University of Pittsburgh


    This talk will provide an overview of quantitative systems pharmacology (QSP), an integrated and iterative computational and experimental approach to drug discovery, that was recently implemented in several drug discovery programs. Specifically, the speaker will discuss the evolution of a human, 3-D, 4-cell type, microfluidic, liver microphysiology system (MPS) as a key experimental component of the institution’s metastatic breast cancer and liver disease programs.


    Metastatic breast cancer involves intravasation, extravasation and “seed and soil” growth establishment in the target organ. Initial studies are being investigated in the human liver MPS by exploring the seed and soil growth and drug sensitivity using the wild-type estrogen receptor alpha (ESR1) and two of the most common mutations, D538G and Y537S, in comparison to experiments performed in 2-D, where the research team explored distinguishable phenotypes that these mutations may confer using genome-editing methods. Results from completed and in-progress studies will be reviewed.

    3:30 - 3:50 p.m.           Break


    3:50 p.m.

    Microvessel-Based 3D Assays of Angiogenesis

    James B. Hoying, PhD, FAHA

    Chief of the Division of Cardiovascular Therapeutics at the Cardiovascular Innovation Institute and President & CEO of Angiomics, Inc.; Chief Scientist, Advanced Solutions Life Sciences, University of Louisville


    Tissue health and disease involve complex interactions between the microvasculature, stroma, and parenchyma of the tissue. The microvasculature itself requires a dynamic interplay between vascular and perivascular cell types to maintain proper form and function.


    In this presentation, the speaker will discuss a versatile, enabling assay platform uniquely positioned to assess an integrated angiogenesis response in a complex environment. Involving the use of intact, isolated human microvessels in a 3-D stromal environment, the assay platform recapitulates native angiogenesis for use in phenotypic screens of different neovascular behaviors. The system is based on bona fide angiogenic sprouting and neovessel growth from isolated, intact parent microvessels that retain all intrinsic vascular and perivascular cells within a 3-D matrix environment. This model system has been effectively used to identify and characterize putative angiogenic factors and inhibitors, evaluate microvascular instability, and define tissue dynamics during angiogenesis. It is compatible with high-content analysis modalities and has a proven utility in a variety of research and pharmaceutical applications. In addition, the microvessels are showing promise in regenerative medicine and tissue fabrication as a promising vascularizing solution.


  • Wednesday, September 27                                                         +

    8:30 a.m.

    Conference Welcome & Live Broadcast Start

    James C. Foster

    President, Chairman, CEO, Charles River




    9:00 a.m.

    A Unifying Model to Explain Primary and Compensatory Immune Resilience of Cancer

    Francesco Marincola, MD, FACS

    Distinguished Research Fellow in Immuno-Oncology, AbbVie


    Available data suggest that three landscapes best portray the cancer microenvironment: an immune-active, an opposite immune-deserted, and an intermediate immune-depleted. This trichotomy is observable across most solid tumors, suggesting that convergent evolutionary adaptations determine the survival and growth of cancer in the immune competent host. The mechanisms allowing persistence of cancer in the immune-active cluster are referred to as compensatory immune resistance (CIRes). Conversely, survival of cancer in the immune-silent environment is referred to as primary immune resistance (PIRes).


    To explain CIRes and PIRes, several models have been proposed that largely outnumber the fewer immune landscapes. In this presentation, the speakers will share how they the research team came to build a navigational map of cancer to assign distinct immune-resistance models to the respective immune-landscape. The survey confirmed that immune suppression strictly goes hand-in-hand with immune activation in the favorable landscape, while the silent landscape is characterized by lack of immune modulation and by a lean oncogenic process that permits growth without activation of the host’s defense mechanisms.

    10:00 - 10:20 a.m.       Break


    10:20 a.m.

    Translating Animal Studies to Successful Human Therapies

    James M. Wilson, MD, PhD

    Professor, Internal Medicine and Pathology & Laboratory Medicine; Director, Gene Therapy Program, Perelman School of Medicine, University of Pennsylvania


    11:20 a.m.

    Genetic Screens to Study Cancer Biology

    David M. Sabatini, MD, PhD

    Member, Whitehead Institute; Professor of Biology, MIT; Investigator of the Howard Hughes Medical Institute; Senior Associate Member, Broad Institute

    12:20 - 1:30 p.m.          Break

    1:30 p.m.                      AFTERNOON BREAKOUT SESSIONS (see schedule)

    4:50 p.m.                      Closing Remarks; Live Broadcast Ends

    5:30 p.m.                      Reception

    Wednesday Track 1
    Improving Translatability of Animal Models in Drug Discovery


    1:30 p.m.

    A Diet-Induced Animal Model of Nonalcoholic Fatty Liver Disease

    Arun Sanyal, MD

    Professor, Department of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University


    Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease and a growing indication for liver transplantation for end-stage liver disease as well as liver cancer. There are currently no approved therapies for nonalcoholic steatohepatitis (NASH). While a large number of therapeutic targets have been identified, there is a need for viable preclinical animal models that recapitulate all stages of NASH development and progression, and that recapitulate the human disease with respect to inducers, liver histology, activation of pathways known to be relevant to human disease, and a transcriptomic profile similar to that in humans.


    This presentation introduces a model where the phenotype was originally noted in a B6129SF2/J mice family and which is now shown to meet the above noted criteria in a consistent manner through brother-sister inbreeding to create an isogenic mouse strain. Study data indicate that this mouse captures the key elements of human disease and provides a tool to better understand the inter-relationships between pathways with disease progression, and to test the therapeutic potential of individual or combination therapies for related disease.

    2:30 p.m.

    Exercise Capacity, Aging, and Longevity

    Lauren Koch, PhD

    Associate Professor of Anesthesiology; Principle Investigator, University of Michigan, Ann Arbor


    Over the past few decades several large-scale epidemiological studies have shown that high performance on tests of maximal exercise capacity associates with lower all-cause morbidity and mortality. Concomitantly, maintaining an aerobic-based exercise program is a primary recommendation for the prevention and treatment of chronic disease, and one of the most important interventions for successful aging and longevity. Yet, there is wide interindividual variation for exercise capacity, and up to 20% of human subjects are considered “exercise resistant” (i.e., demonstrate little or no change in maximal oxygen consumption [VO2max] in response to training).


    In this presentation, the speakers will review their recent research, which demonstrates that exercise genomic rat models via selection provide unbiased support that variation in exercise capacity (either intrinsic or acquired) correctly forecasts future health and disease across aging. Moreover, this original and translational animal model system represents a basic yet highly individualized underlying process that can be probed repeatedly across lifetime for more detailed information regarding efficacy and specificity within drug discovery and development.


    3:30 - 3:50 p.m.           Break


    3:50 p.m.

    Diet Preferences in Large Animal Models of Cardiovascular Disease: Does it Matter?

    Anthony G. Comuzzie, PhD, FTOS

    Executive Director, The Obesity Society


    Most of the animal-based research related to diet and risk associated with cardiovascular disease, obesity, and diabetes has focused primarily on the impact of specific dietary fats. While these efforts have recently expanded to examine the impact of carbohydrates and proteins, the potential contribution of overall palatability on the feeding behavior of research animals has largely been ignored. Data from multiple feeding studies that have been conducted in the baboon suggest the importance of considering palatability in the development of dietary challenges to investigate the impact of nutritional components on cardiometabolic health.


    This presentation will review the speaker’s research, which indicates that the research animals’ pattern of consumption, an important component in the mechanism of nutritional impact on disease risk, may vary depending on the palatability of the diet. The researchers have found that by increasing the palatability of challenge diets, simply by adding fruit flavoring and baking, they can obtain a pattern of consumption that is most likely more like that seen in humans, and as a result more successfully drives the development of the clinical manifestations of interest.


    Wednesday Track 2
    Non-Traditional Animal Models for Drug Discovery


    1:30 p.m.

    Small Molecule Discovery for Regenerative Medicine: The Essential Role of
    Non-Traditional Animal Models

    Kevin Strange, PhD

    Novo Biosciences


    Regenerative medicine is the field of biomedical R&D and clinical practice focused on repairing, regenerating, or replacing tissues and organs that have been lost or damaged due to injury, disease, and the degenerative changes associated with aging. The discovery and development of small molecules capable of activating innate tissue repair and regenerative processes is a newly emerging field in regenerative medicine. Arguably, the most economical and efficient strategy for development of small molecules with regenerative medicine applications is to use “non-traditional” animal models for both target- and phenotype-based drug discovery.


    Novo Biosciences, Inc. and the MDI Biological Laboratory have undertaken a focused effort to develop lead small molecules capable of activating endogenous tissue regenerative mechanisms. These efforts are greatly facilitated by RegenDbase, a unique computational biology and bioinformatics tool, as well as the use of the zebrafish for phenotype-based small molecule screening and discovery. This presentation will examine the discovery and characterization of MSI-1436, the first and, to date, only small molecule capable of inducing regeneration in the adult mammalian heart following ischemic injury.

    2:30 p.m.

    Bugs as Drugs

    Paul Miller, PhD

    Chief Scientific Officer, Synlogic Therapeutics


    3:30 - 3:50 p.m.           Break


    3:50 p.m.

    Rapid 3D Bioprinting of Blood Vessel Network and Microphysiological Systems

    Shaochen Chen, PhD

    Professor, University of California, San Diego


    This presentation will review the speakers’s recent research efforts in rapid continuous projection 3-D bioprinting to create 3-D scaffolds using a variety of biomaterials. These 3-D biomaterials are functionalized with precise control of micro-architecture, mechanical, chemical, and biological properties. Such functional biomaterials allowed for investigation of cell-microenvironment interactions at nano- and micro-scales in response to integrated physical and chemical stimuli. From these fundamental studies, both in vitro and in vivo microphysiological systems can be created, including a human liver tissue for tissue regeneration, disease modeling, and drug discovery.


    To vascularize these engineered tissues, the researchers have developed a prevascularization technique using the rapid 3-D bioprinting method. With regionally controlled biomaterial properties, the endothelial cells formed lumen-like structures spontaneously in vitro. In vivo implantation demonstrated the survival and progressive formation of the endothelial network in the prevascularized tissue. Anastomosis between the bioprinted endothelial network and host circulation was observed with functional blood vessels featuring red blood cells. With superior bioprinting speed, flexibility and scalability, this new prevascularization approach can be broadly applicable to the engineering and translation of various functional tissues.


    Wednesday Track 3
    How Reverse Translation Has Influenced Animal Model Creation


    1:30 p.m.

    Models of Vascular Pathologies – Extrapolation To and From Human Diseases

    Alan Daugherty, PhD, DSc, FAHA

    Associate VP for Research, Senior Associated Dean for Research, College of Medicine Chair, Department of Physiology; Director, Saha Cardiovascular Research Center; Gill Foundation Chair in Preventive Cardiology, Professor of Medicine and Physiology, ATVB, Editor-in-Chief, University of Kentucky


    Atherosclerosis is the underlying cause of cardiovascular events and the major cause of morbidity and mortality in developed countries. The bulk of contemporary atherosclerosis literature is focused on mouse models performed in mice lacking either LDL receptor or ApoE. While these studies have determined potential therapeutic targets, there are limited examples of targets identified or validated in mouse models that have subsequently led to human interventions. A major shortcoming of common animal models is their failure to develop atherosclerosis that accurately mimics lesions in advanced stages and to recapitulate acute thrombotic events associated with atherosclerosis that trigger overt clinical symptoms.


    Aortic aneurysms are less common than atherosclerotic diseases, but represent an area of considerable unmet medical need. In this presentation, the speaker will review three common mouse models of abdominal aortic aneurysms and discuss how a lack of information on the natural history of the human disease hinders the determination of the fidelity of these animal models. Discussion will include current clinical trials and their potential role in increasing the diminutive number of therapeutic targets for these diseases.

    2:30 p.m.

    Recapitulating Human Patient Mutations in Mouse Oncology Models

    Dejan Juric, MD

    Director of Translational Research at Termeer Center for Targeted Therapies, Mass General Hospital; Professor, Harvard Medical School


    3:30 - 3:50 p.m.          Break


    3:50 p.m.

    Rat Models of Susceptibility to Complex Diseases: A Solution to Eroom’s Law

    Steven Britton, PhD

    Professor of Anesthesiology, Professor of Molecular and Integrative Physiology, University of Michigan


    Since 1950, the inflation-adjusted industrial development costs per drug increased nearly 100-fold to arrive at 1 billion dollars. This trend, termed Eroom’s Law (i.e., Moore’s Law backwards), is an enigma because huge high-throughput technological gains should have raised the efficiency of research and development (R&D). A recent quantitative decision-theoretic model of the R&D process led to the conclusion that Eroom’s is explained by: 1) limited creation and use of valid animal models of disease, and 2) too much reliance on reductionist molecular approaches that are devoid of the very complexity that embodies emergent disease conditions.


    This presentation will offer an alternative – an integrative, theory-based, approach to resolving complex diseases that builds upon an evidenced link between low exercise capacity and high morbidity and mortality. Attendees will learn about a predictive test of this hypothesis, which demonstrates that two-way selective breeding of genetically heterogeneous rats for low and high intrinsic treadmill running capacity (used as a surrogate for energy transfer) also produces rats that differ for risk of obesity, diabetic neuropathy, metabolic syndrome, and reduced longevity.



© 2017 Charles River Laboratories International, Inc.