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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Center Core Grants (P30)
Project #
1P30GM106391-01
Application #
8543902
Study Section
Special Emphasis Panel (ZGM1-TWD-C (C3))
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$132,523
Indirect Cost
$46,189
Name
Maine Medical Center
Department
Type
DUNS #
071732663
City
Portland
State
ME
Country
United States
Zip Code
04102
Ames, Jacquelyn J; Contois, Liangru; Caron, Jennifer M et al. (2016) Identification of an Endogenously Generated Cryptic Collagen Epitope (XL313) That May Selectively Regulate Angiogenesis by an Integrin Yes-associated Protein (YAP) Mechano-transduction Pathway. J Biol Chem 291:2731-50
Liaw, Lucy; Prudovsky, Igor; Koza, Robert A et al. (2016) Lipid Profiling of In Vitro Cell Models of Adipogenic Differentiation: Relationships With Mouse Adipose Tissues. J Cell Biochem 117:2182-93
Dadwal, Ushashi; Falank, Carolyne; Fairfield, Heather et al. (2016) Tissue-engineered 3D cancer-in-bone modeling: silk and PUR protocols. Bonekey Rep 5:842
Anunciado-Koza, Rea P; Higgins, David C; Koza, Robert A (2016) Adipose tissue Mest and Sfrp5 are concomitant with variations of adiposity among inbred mouse strains fed a non-obesogenic diet. Biochimie 124:134-40
Lecka-Czernik, Beata; Rosen, Clifford J (2016) Skeletal integration of energy homeostasis: Translational implications. Bone 82:35-41
Krebs, Luke T; Norton, Christine R; Gridley, Thomas (2016) Notch signal reception is required in vascular smooth muscle cells for ductus arteriosus closure. Genesis 54:86-90
Young, K; Krebs, L T; Tweedie, E et al. (2016) Endoglin is required in Pax3-derived cells for embryonic blood vessel formation. Dev Biol 409:95-105
Calabrese, Gina; Mesner, Larry D; Foley, Patricia L et al. (2016) Network Analysis Implicates Alpha-Synuclein (Snca) in the Regulation of Ovariectomy-Induced Bone Loss. Sci Rep 6:29475
Martinez, M Elena; Karaczyn, Aldona; Stohn, J Patrizia et al. (2016) The Type 3 Deiodinase Is a Critical Determinant of Appropriate Thyroid Hormone Action in the Developing Testis. Endocrinology 157:1276-88
Anunciado-Koza, Rea P; Manuel, Justin; Koza, Robert A (2016) Molecular correlates of fat mass expansion in C57BL/6J mice after short-term exposure to dietary fat. Ann N Y Acad Sci 1363:50-8

Showing the most recent 10 out of 40 publications