At our COBRE Center and Institute, the large majority of investigations employ and develop transgenic and knockout mouse models for human disease. In keeping with our Center's theme, these typically are designed towards studying stem and/or progenitor cells within select tissues, lineages and pathways of prime interest. It is becoming increasingly clear, however, that many cell and molecular regulators can also affect metabolism and bioenergetics in substantial and important ways. This can reveal unexpected "off targets", rule-in major circumscribed roles for new metabolic regulators, or rule-out pleiotropic effects. In year-4 of Phase-ll, in response to increasing needs for metabolic phenotyping, we designed and deployed a new Physiology Core Facility in order to provide consolidated and highly informed analyses of mouse model biomarkers and analytes, metabolism;global metabolism and skeletal features;cell and mitochondrial respiration;and hematology parameter analyses. Importantly, this new facility is headed by a highly productive and informed clinician scientist with exceptional experience in bone, adipocyte, endocrine and metabolic biology (Dr. C Rosen, Core Director). Expert research staff also are in-place with 15+ yrs combined experience. Specific goals/aims of this now fully active core are four-fold: 1- Offer a needs-based arrays of enzyme-linked, colorimetric and radioimmunoassays for comprehensive hematologic, metabolic and skeletal phenotyping;2- Perform complete metabolic phenotyping for genetic models through the use of metabolic cages plus DXA scanning approaches;3- Assess cellular and mitochondrial bioenergetics via analysis of oxidative phosphorylation and glycolysis of isolated cells and mitochondria;4- Provide investigators with full reports and counsel detailing the metabolic profiling of mutant strains, total and fractional tissue mass, energy expenditure, biochemical markers and substrate utilization. As this core now ramps-up, biomarker/analytic demands are increasing;mouse metabolic chambers are reserved 3-monthsout;and needs for cell/mitochondrial respiration and hematology analyses are steadily increasing. Six months- in, exciting findings already are being generated for publications and grants. Extensive prior experience (and success) with clinical laboratory endeavors further underscores strengths in developing plans for core income, and self-sustainability. Institutional support for this exciting new core facility also has been strong (and new institutional faculty hires in metabolics are scheduled in a recently approved new 5- year research strategic plan). Overall, this core will effectively and efficiently provide investigators with comprehensive metabolic phenotyping.

Public Health Relevance

The majority of COBRE Center and Institute investigators have developed incisive mouse models for human disease. Needs for critically assessing metabolic features therefore have increased. Our Physiology Core now meets these demands by providing analyses of biomarkers/analytes, hematology, skeletal features, overall metabolism and cellular respiration. Importantly, this includes expert interpretation of data, training and follow-up council.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Center Core Grants (P30)
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Special Emphasis Panel (ZGM1-TWD-C (C3))
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Maine Medical Center
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