Achievements & Developments of Metabolic Phenotyping and

In Vivo Imaging Cores

Thomas Balon, Ph.D.tombalon@bu.edu BUMC Faculty MeetingDecember 1, 2015

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

Instrumentation-EchoMRI-700™ What We Have

•Determination oftotal body fat

lean massbody fluidstotal body water

in live rats/mice up to 700 grams

What Is it Good For

Old vs. New System•larger range of weights with greater precision (smaller rodents)•faster resolution times

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

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

Instrumentation-CLAMS

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

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:e01283802. 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 160:105-183. 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 124:2099-1124. 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

Instrumentation-Thermoneutrality Chambers

Donated

Usage Calendar year Days of use

2014 195 2015 (11 Mo.) 316

Challenges – Major user is leaving (100% usage loss)

Resolution – New Instrument

Instrumentation-Thermoneutrality Chambers

Instrumentation-IVIS

Bioluminescence Fluorescence

Usage– Calendar year Minutes of use

20123132201360932014 6581 2015 (11 Mo.) 3872

Challenges – Major user left for each of past 2 years

Instrumentation-IVIS Spectrum

Resolution – New users including non-academic Current contracts

– Arietis– Pixabio

Under negotiation – Selecta

Instrumentation-IVIS Spectrum

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 Clin Oncol 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 Clin Inv 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.

Partial List of Publications using IVIS

Seminars for More Methods