The COBRE grant-Mammalian Hibernation: A Path Towards a Center for Transformative Research in Metabolism (Supported by the NIGMS of the NIH under award number P20GM130443) A review of events leading to UAF’s COBRE Phase 1 award: • Submitted January 2018, Revised January 2019. • 2018 submission funded July 16, 2019 $11.8 M over 5 years. • Eligible for two 5-year renewals (for a total of 15 years) and an additional $17 M Dr. Kelly Drew, Principal Investigator June 23, 2020
Introducing Members of our External Advisory Committee Dr. Sven O. Ebbesson, Dr. Margaret E. Rice , Professor Emeritus who Professor and Vice Chair for formerly served as a Professor Research in the Dept. of at UAF in the areas of medical Neuroscience and Physiology science, neuroscience, and at the NYU Grossman School marine science. of Medicine. Dr. Detlev Boison, Professor Dr. David A. Lathrop, and Vice Chair of Research and Consulting Scientist and Training at the Dept of former Chief of the Heart Neurosurgery, RWJMS and New Failure and Arrhythmias Jersey Medical School, at Branch in the Division of Rutgers, The State University of Cardiovascular Sciences at New Jersey. NHLBI of the NIH. Dr. Thomas Kilduff, Director of the Center for Neuroscience at SRI International.
Overall Project Summary Establish a self-sustaining, multi-disciplinary biomedical research center that builds on our proven history of hibernation research, infrastructure, and long-term commitment and applies what has been learned about the underlying physiological mechanisms in hibernation into treatments that advance human metabolic health. Support the research and career development of both experienced as well as new investigators in all stages of translational studies related to hibernation, metabolism, and microbiome in biomedical research. TRiM is the first biomedical research program in the U.S. to adopt hibernation as a model of natural adaptations in metabolism as an approach to treat metabolic disease.
Overall Specific Aims-Build infrastructure and support research until it is competitive SA1: Establish an organizational structure and research infrastructure comprised of an Administrative Core, a Microbiome Core (AIMS), and a Health and Metabolism Research Core that will support and promote a multidisciplinary framework that defines mechanisms of metabolic adaptations in hibernating mammals. SA2: Enhance the careers of experienced project leaders and new investigators leading pilot projects by using effective mentoring and collaboration plans involving established NIH-funded investigators that will allow new investigators to submit high quality, competitive proposals to NIH for their individual research grants. SA3: Support research and pilot projects to develop an understanding of hibernation mechanisms - physiological, genetic, and gut microbial - and define how these mechanisms may play a role in treating metabolic disease and muscle atrophy or sarcopenia . SA4: Support clinical research projects related to the theme of this Center.
Michelle Rizk (Acting)
Introductions
“Center” of Transformative Research in Metabolism (TRiM)
Pubmed search-Hibernation and Alaska
We invite you to take a journey in Translational Hibernation Research at UA as we describe: • What UAF/UAA has done… • Who we are now • What we are doing… • Where we are going…
What we have done Exploring hibernation as a unique adaptation of northern mammals to survive Alaska’s long winters and working to translate this fundamental knowledge to enhance human health.
What have we learned? Hibernation is a highly regulated adaptive, and reversible state of metabolic flexibility and anabolic sensitivity from which to discover novel therapeutic targets (Carey et al. 2003) 12
What have we learned? Hibernation allows northern mammals to comfortably survive Alaska’s long winters. Through research, we are learning that hibernating mammals: • Drop their body temperature below freezing, • Preserve muscle mass despite not eating or moving for 8 months, and • Switch from carbohydrate to fat metabolism during hibernation. We have also discovered: • Which genes turn on and off during hibernation, and • How body chemicals change during hibernation.
Why is the study of hibernation important to human health and Alaskan health? Hibernation science has novel cues to treat metabolic disease and promote healthy aging Sarcopenia Disuse muscle atrophy Cachexia Anorexia Obesity Cardiac arrest and stroke Type 2 diabetes Osteoporosis Cardiac disease Fatty liver
Who we are
Introducing TRiM's Research Investigators and their Projects P.I. Vadim Fedorov, PhD, Genomics, UAF Project 1: Post transcriptional mechanisms of muscle atrophy prevention in hibernating mammals . P.I. Khrys Duddleston, PhD, Microbiology, UAA Dr. Kelly Drew, Project 2 : Microbial provision of essential amino TRiM Principal Investigator acids, protein conservation in hibernation UAF P.I. Robert “Trey” Coker, PhD, Clinical Nutrition and Exercise Physiology, UAF Project 3: Nutritional strategies for metabolic health in aging
TRiM's Vision, Mission, and Values Our Vision: Translating hibernation research to improve human health. Our Mission: To seek fundamental knowledge about the nature and behavior of hibernating mammals and the translation of that knowledge to enhance human health, lengthen life, and reduce illness and disability. Our Values: “TRiM” ➢ T for Team Science : Multiple, diverse perspectives, and expertise empowers great and innovative science. ➢ R for Respect: Respecting each person for their unique perspective, expertise, and contribution to the overall effort. ➢ I for Integrity: Helping people to be the best at what they do best and keeping a high ethical standard. ➢ M for Motivation: Motivating oneself and others to do the job better than it has been done before in order to create a cycle of empowerment and accomplishment for both the scientific community and the Institute.
What we are doing Translating hibernation research to improve human health.
Alaska Senior Population, 2010 to 2019 Population 60+ Average Growth Rate 2010 – 2019: 5.8% per year and 52%, 2010-2019 Source: Alaska Department of Labor and Workforce Development, Research and Analysis Population Estimates, 2010-2019 160,000 Alaska is the state with the fastest growing senior population per capita. Alaskans age 60+ are the fastest growing age demographic in the state. Within the senior 140,000 population, people age 70-74 are growing rapidly, increasing at an annual rate of 10% as baby boomers come of age. 120,000 100,000 80,000 60,000 40,000 20,000 0 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 60-64 65-69 70-74 75-79 80-84 85+
Projected Alaska Senior Population by Age Cohort, 2020-2045 Population 60+ Average Annual Growth Rate: 5.25% (or 21% total older adult population increase, 2020 to 2045) Source: Alaska Department of Labor and Workforce Development, Research and Analysis, Population Projections, Middle Scenario From 2020 to 2045, Alaska’s older adults will increase by 30,708 people and comprise 21% of the state’s total population in 2045. During that time, the fastest growing age segment will be persons age 85+. 200,000 180,000 160,000 140,000 120,000 100,000 80,000 60,000 40,000 20,000 - 2020 2025 2030 2035 2040 2045 60-64 65-69 70-74 75-79 80-84 85+
Hibernation Science Offers Clues to Understand Frailty and Age-Related Health Conditions Sarcopenia Disuse muscle atrophy Cachexia Anorexia Obesity Cerebral Ischemia and stroke Type 2 diabetes Osteoporosis Cardiac disease Fatty liver Fall Risk
22 • Approach – Hibernation Science → Understanding frailty In disease and understanding degeneration/regeneration of neurons and myocytes in aging. Frailty exacerbates morbidity and mortality associated with disease (acute – such as after a cardiac arrest, or chronic such as metabolic syndrome Type 2 Diabetes) as well as aging. • Our Goal – Translate hibernation science platforms into therapies and diagnostics providing numerous partnering opportunities
Health and Metabolism Research Core (HaMR) & Key Personnel Dr. Cory Williams, Core Leader, UAF Dr. Carl Murphy, Molecular Imaging Facility Manager, UAF Dr. Øivind Tøien, Manager of Animal Instrumentation, UAF
Advanced Investigations in Microbiome Sciences Core & Key Personnel Dr. Brandon Briggs, Core Leader, UAA Eric Henderson, B.S., Lab Manager Tyler Fox, B.S., Laboratory Technician
Administrative Core & Key Personnel Dr. Kelly Drew, Principal Investigator, UAF Dr. Anya Goropashnaya, Research Professional, UAF Dr. Bahareh Barati, Biostatician, UAF Denise Daniello, MA, Program Coordinator, UAF Brittney Wilhite, MS, Fiscal Technician and Admin Assistant, UAF
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