Achievements & Developments of Metabolic Phenotyping and In Vivo Imaging Cores

1. Achievements & Developments of Metabolic Phenotyping and In Vivo Imaging Cores Thomas Balon, Ph.D. tombalon@bu.edu BUMC Faculty Meeting December 1, 2015

2. Introduction • Other cores • Cellular Imaging Cores – Mike Kirber mkirber@bu.edu • Immunohistochemistry – Natalie Bitar natbitar@bu.edu • Metabolomics – Anqi Zhang • anqi@bu.edu • High Throughput Screening Core - TBA • Analytical Instrumentation Core – Lynn Deng lynndeng@bu.edu later presentation Matt Aumau115@bu.edu

3. What We Have What Is it Good For • Determination of • total body fat • lean mass • body fluids • total body water • in live rats/mice up to 700 grams • Instrumentation-EchoMRI-700™ Old vs. New System • larger range of weights with • greater precision (smaller rodents) • faster resolution times

4. Instrumentation-EchoMRI-700™ • Usage • Calendar year Minutes of use 2012 1500 2013 2395 2014 2792 2015 (11 Mo.) 3138 • Challenges - Major user is leaving (44% usage loss) • Resolution - 4 new users & Contract with Harvard for Carcass analysis

5. Instrumentation-CLAMS • measurement of metabolic rate (caloric expenditure) • determination of substrate used (fat / carbohydrate) • assessment of activity patterns • greater sensitivity (sleep detection)

6. Instrumentation-CLAMS • Usage • Calendar year Days of use 2012 29 2013 60 2014 43 2015 (11 Mo.) 50 • Challenges - Major user is leaving (74% usage loss) • Resolution -2 new users & Characterization of 2 new strains

7. Partial List of Publications using Echo and CLAMS 1. Kleckner AS, Wong S, Corkey BE. 2015. The Intra- or Extracellular Redox State Was Not Affected by a High vs. Low Glycemic Response Diet in Mice. PLoS One 10:e0128380 2. McDonald Meghan E, Li C, Bian H, Smith Barbara D, Layne Matthew D, Farmer Stephen R. 2015. Myocardin-Related Transcription Factor A Regulates Conversion of Progenitors to Beige Adipocytes. Cell 160:105-18 3. Shimizu I, Aprahamian T, Kikuchi R, Shimizu A, Papanicolaou KN, et al. 2014. Vascular rarefaction mediates whitening of brown fat in obesity. The Journal of Clinical Investigation 124:2099-112 4. Watkins AA, Yasuda K, Wilson GE, Aprahamian T, Xie Y, et al. 2015. IRF5 deficiency ameliorates lupus but promotes atherosclerosis and metabolic dysfunction in a mouse model of lupus-associated atherosclerosis. J Immunol 194:1467-79

8. Instrumentation-Thermoneutrality Chambers Donated

9. Instrumentation-Thermoneutrality Chambers • Usage • Calendar year Days of use 2014 195 2015 (11 Mo.) 316 • Challenges – Major user is leaving (100% usage loss) • Resolution – New Instrument

10. Instrumentation-IVIS Bioluminescence Fluorescence

11. Instrumentation-IVIS Spectrum • Usage • Calendar year Minutes of use 2012 3132 2013 6093 2014 6581 2015 (11 Mo.) 3872 • Challenges – Major user left for each of past 2 years

12. Instrumentation-IVIS Spectrum • Resolution – New users including non-academic • Current contracts • Arietis • Pixabio • Under negotiation • Selecta

13. Partial List of Publications using IVIS J. Richmond, M. Finkel, A. Studwell, F. Little, and W. Cruikshank . Introduction of Pro-interleukin-16 inhibits T lymphoblastic leukemia growth in mice. Journal of Cancer Research and Clinical Oncology. J Cancer Res ClinOncol 137:1581–1585. Wilson, AA, Murphy, GJ, Hamakawa, H, Kwok, LW, Srinivasan, S, Hovav, AH, Mulligan, RC, Amar, S, Suki, B and Kotton DN. Amelioration of emphysema in mice through lentiviral transduction of long-lived pulmonary alveolar macrophages. J ClinInv 120(1):379–389. Bais MV, Wigner N, Young M, Toholka R, Graves DT, Morgan EF, Gerstenfeld LC, Einhorn TA BMP2 is essential for post natal osteogenesis but not for recruitment of osteogenic stem cells. Bone. 45(2): 254-66.

14. Seminars for More Methods