Exploring Frontiers: Predicting Biology Webinar
Model systems have been used to successfully pioneer foundational research, leading not only to an advanced understanding of biological systems but also to translational breakthroughs. However, only a portion of scientific results seen in mice are mirrored in humans. How can we better infer which observations will hold true in both systems?
This webinar included speaker presentations and a lively panel discussion on the challenges, opportunities and next steps needed to move the needle in modeling mouse to human inference. See below for the agenda and speaker information.
Wednesday, October 6 (Pacific Time)
8:50 - 9:00am - Virtual meeting log-in
9:00 - 9:05am - Kathryn Richmond, The Paul G. Allen Frontiers Group, Welcome and introductory remarks
9:05 - 9:30am - Shai Shen-Orr, Technion Medicine
9:30 - 9:55am - Nadia Rosenthal, The Jackson Laboratory
9:55 - 10:05am - Break
10:05 - 10:30am - Douglas Brubaker, Purdue University
10:30 - 11:00am - Panel Discussion and Q&A, moderated by Stacey Finley, University of Southern California
Douglas Brubaker, Ph.D.
"Computational humanization of latent variables for cross-species modeling"
Abstract: Direct mapping of molecular-to-phenotype relationships across species often fails to yield translatable insights into disease pathobiology, therapeutic mechanisms, and rules of life. To address this challenge, systems biology methods have been proposed to enhance the predictive capability of model organisms and in vitro systems. Our approach to these challenges, termed computational humanization, aims to translate models of animal data to humans via computational integration of animal and human-context measurements. In this talk I will discuss our work developing latent variable methods for cross-species modeling and ongoing efforts to better translate these models to heterogeneous human populations.
Bio: Douglas Brubaker is an Assistant Professor in the Weldon School of Biomedical Engineering and Core Faculty Member in the Regenstrief Center for Healthcare Engineering at Purdue University. His lab develops systems biology approaches to understand mechanisms of host-microbiome interactions and approaches to translate biological observations from model systems to humans. His research is supported by Open Philanthropy and the National Science Foundation. Professor Brubaker completed post-doctoral studies in the Department of Biological Engineering at MIT and holds a Ph.D. in Systems Biology and Bioinformatics from Case Western Reserve University.
Nadia Rosenthal, Ph.D.
The Jackson Laboratory
"The mouse ascending: Translating human genetic variation to function"
Abstract: Inbred mice have been only modestly successful in modelling widely divergent clinical outcomes in human disease, due to their limited genetic background. As host genetics plays a significant role in disease susceptibility, pathogenic infection and treatment success, preclinical models that reflect human genetic variation are crucial for predicting disease course and developing precision therapies.Interbred panels of mouse strains offer allelic diversity that mimics human genetic variation with the requisite statistical power and resolution for dissecting complex traits. Mouse diversity resources combined with gene editing offer exciting prospects for creating a future of predictive biology for individualized disease prevention and treatment.
Bio: Nadia Rosenthal is Scientific Director of The Jackson Laboratory in Bar Harbor, Maine. She obtained her PhD from Harvard Medical School, where she later directed a biomedical research laboratory, then headed the European Molecular Biology Laboratory (EMBL) campus in Rome. She founded EMBL Australia as its Scientific Head, and was Founding Director of the Australian Regenerative Medicine Institute in Melbourne. She is an EMBO member, a Fellow of the UK Academy of Medical Sciences and of the Australian Academy of Health and Medical Science. She also holds a Chair in Cardiovascular Science at Imperial College London.
Rosenthal’s research team focuses on the role of growth factors, stromal cells and the immune system in the resolution of tissue injury for applications in regenerative medicine. They have recently shown how modifying the profile of immune cell infiltration can facilitate or prevent tissue repair and have demonstrated the power of harnessing mouse genetic diversity to identify new genetic pathways in the varied response to cardiovascular disease. Over the past year, they have turned their expertise in mouse genetics toward creating more precise mouse models for SARS-CoV-2.
Shai Shen-Orr, Ph.D.
Technion – Israel Institute of Technology
"Found in translation: Leveraging machine learning models to bridge the cross-species"
Abstract: Mice are the most widely used and cost-effective model to study human diseases. Yet, from a clinical perspective, successful therapeutic experiments in mice often fail in human clinical trials. Despite the considerable time and expense involved, efforts to improve human-disease modeling have focused on developing mice that more closely mimic human biology. In contrast, there have been scarce attempts to develop in silico methodologies for overcoming translational challenge and this is despite an explosion of data.
Here we present Found in Translation (FIT), a data-driven machine learning model that, given a mouse gene expression experiment and a corpus of prior data comparing mouse/human experiments, predicts the biology in the mouse model relevant to the analogous human condition. FIT can increase identification of human relevant genes by up to 50%. The use of computational modeling to bridge the cross-species gap can reduce risk, save time and improve utilization of pre-clinical models.
Bio: Shai Shen-Orr is an Associate Prof. at the Faculty of Medicine at the Technion – Israel Institute of Technology, where he heads the Systems Immunology & Precision Medicine laboratory since 2012. His research is focused on charting the immune system landscape – namely the principles by which the immune system varies over time as a function of environment and genetics. For this, his lab develops novel computational methodologies, empowering human immune monitoring for precision medicine.
Prof. Shen-Orr received a BSc from the Technion in Information Systems (1999), an M.Sc. in Bioinformatics at the Weizmann Institute of Science (2002), a Ph.D. from Harvard University in Biochemistry (2007) and performed his postdoctoral studies at Stanford University with Prof. Mark Davis and Prof. Atul Butte.
Prof. Shen-Orr is also the Chief Scientist of CytoReason. CytoReason is building a machine learning model of the immune system; which it applies to drug development.
Stacey Finley, Ph.D.
University of Southern California
Dr. Stacey D. Finley is the Gordon S. Marshall Early Career Chair and Associate Professor of Biomedical Engineering at the University of Southern California. Dr. Finley is also the Founder and Director of the Center for Computational Modeling of Cancer at USC. Dr. Finley received her B.S. in Chemical Engineering from Florida A & M University and obtained her Ph.D. in Chemical Engineering from Northwestern University. She completed postdoctoral training at Johns Hopkins University in the Department of Biomedical Engineering. Dr. Finley joined the faculty at USC in 2013, and she leads the Computational Systems Biology Laboratory. Dr. Finley has joint appointments in the Department of Chemical Engineering & Materials Science and the Department of Quantitative and Computational Biology, and she is a member of the USC Norris Comprehensive Cancer Center. Dr. Finley is also a standing member of the MABS Study Section at NIH.
Dr. Finley’s research group uses multiscale computational models to answer unresolved questions about how behave and to identify new ways to control cell behavior. Dr. Finley has applied these models to study signaling that promotes angiogenesis, metabolic pathways that cells use to proliferate, and immune cell activation.
Selected honors. 2016 NSF Faculty Early CAREER Award; 2016 Young Innovator by the Cellular and Molecular Bioengineering journal; Leah Edelstein-Keshet Prize from the Society of Mathematical Biology; Junior Research Award from the USC Viterbi School of Engineering; the Hanna Reisler Mentorship Award; 2018 AACR NextGen Star; 2018 Orange County Engineering Council Outstanding Young Engineer; 2021 Elected Fellow of American Institute for Biological and Medical Engineering
Kathryn Richmond, Ph.D., M.B.A
The Paul G. Allen Frontiers Group
Kathryn Richmond directs the overall research portfolio strategy and all grant programs at The Paul G. Allen Frontiers Group, overseeing ~$200M in award funding. In addition, she frequently serves as a reviewer with federal agencies and partner organizations for multidisciplinary ‘frontier’ research programs, and as an invited panel member on topics ranging from science philanthropy to technology development. Since joining the organization in 2012, Richmond has grown the bioscience portfolio, expanded the Allen Distinguished Investigator program and led funding in emerging bioscience and technology areas. She previously served as Director of Enabling Technologies at the Great Lakes Bioenergy Research Center. In that position, she developed and oversaw a diverse portfolio of numerous technologies ranging from "omics" to plant transformation which supported the research needs of its 300 members. Prior to that, Richmond worked as a bench scientist, project lead and industry consultant, garnering two patents and multiple publications. Along with a doctorate in Cell and Molecular Biology from the University of Wisconsin, Madison, Richmond also holds an MBA and attended Stanford University as an American Cancer Society fellow.