Michigan MMPC

PI: Malcolm J. Low, MD, PhD

10/28/19 Adminstrative Core Malcolm Low, MD, PhD –Core Director (Departments of Molecular & Integrative Physiology; Internal Medicine)

Debra Warrick, MS – Administrator

Animal Care and Germ‐Free Mouse Core Robert Sigler, DVM, PhD ‐ Core Director (Unit for Laboratory Animal Medicine)

Robert Dysko, DVM, DCLAM ‐ Core Co‐Director (Unit for Laboratory Animal Medicine)

Kathryn Eaton, DVM, PhD ‐ Core Assoc. Director (Department of Microbiology & Immunology and ULAM) Metabolism and Behavior Core Malcolm Low, MD, PhD ‐ Core Director (Department of Molecular & Integrative Physiology) Nathan Qi, MD, PhD ‐ Core Co‐Director (Department of Molecular & Integrative Physiology) Melanie Schmitt, MS‐ Core Lab Manager

Microvascular Complications Core Eva Feldman, MD, PhD ‐ Director (Department of ) Jeffrey Hodgin, PhD ‐ Co‐Director (Department of Pathology) David Antonetti, PhD ‐ Co‐Director (Department of Ophthalmology & Visual Sciences) Cheng‐mao Lin, PhD ‐ Coordinating Manager (Department of Ophthalmology & Visual Sciences) Microbiome Core Vincent Young, MD, PhD ‐ Core Director (Departments of Internal Medicine; Microbiology & Immunology) Pat Schloss, PhD ‐ Core Assoc. Director (Department of Microbiology & Immunology) Tom Schmidt, PhD ‐ Core Assoc. Director (Departments of Ecology & Evolutionary (LSA); Internal Medicine, Microbiology & Immunology) Christine Bassis, PhD ‐ Research Investigator (Department of Internal Medicine) Service Requests and Fee for Service Revenue

Year 16 FY 2017 Year 17 FY2018 Year 18 FY2019 Totals three years Service Requests (internal) 365 750 775 1890 Service Requests (external) 8 214 123 345 Service Requests (total) 373 964 898 2235

Unique customers (internal) 35 42 39 116 Unique customers (external) 3 8 12 23 Somnio Global Cincinnati Children's Hospital Wayne State University Swiss Federal Institute of Technology University of Kentucky Somnio Global Yale University Somnio Global University of University of Gothenburg Proneurotech, Inc UW ‐ Madison Aarhus University, Denmark West Virginia Univ University of Pennsylvania Yale University Food and Drug Administration NIH‐NIDDK Loyal University, Chicago Pena University of Kentucky PharmaZRI Cornell University Children's Hospital Of Oakland Res Inst. Washington University, St. Louis

Unique customers (total) 38 51 51 140

Revenue (internal) $246,902 $338,923 $291,844 $877,669 Revenue (external) $36,174 $117,700 $130,571 $284,445 Revenue (total) $283,076 $456,623 $422,415 $1,162,114 Additional Performance Metrics

Grants supported by Michigan MMPC for the past three years

73 total NIH grants supported over past three years 60 were R01s 41 were DK grants Additional NIH institutes were: EY, HD, AG, HL, ES, CA, NS, DA, OD, AI, GM and DE

Letters of support written for grant applications: 81

Services provided to academic institutions in 13 states and 3 countries (Sweden, Denmark and Switzerland) Research Updates

Metabolism and Behavior Core Portal vein vs. carotid artery blood sampling OGTT

Nathan Qi Portal vein vs. carotid artery blood sampling IVGTT

Nathan Qi Sable Systems 16 cage Promethion Core

• Standard O2 and CO2 sensors for indirect calorimetry and calculation of EE

• Additional gas sensors for detection of H2, methane and VOC produced by gut bacteria

• Gas sensors for detection of the stable isotopes [13C] & [18O] in exhaled breath (breath tests) Theory and application of breath tests • Based on the detection of ratios between either 13C/12C or 18O/16O in exhaled air • The stable isotopes can reflect either the endogenous tissue pools or artificial enrichment with a variety of 13C or 18O tracer molecules

All other grains, Corn, Fruits, vegetables Cane sugar Including sugar beets

Two distinct photosynthetic pathways in plants cause distinct levels of 13C Breath tests at natural abundance levels of 13C

McCue MD and Welch KC Jr. (2016) J Comp Physiol B 186:265‐285 Breath tests using tracer‐enriched molecules for diagnostic purposes

McCue MD and Welch KC Jr. (2016) J Comp Physiol B 186:265‐285 Oxidative disposal of a bolus of 13C‐glucose

Sable Systems Research Updates

Retinopathy Core Effect of S490A Occludin on Vision

David Antonetti and Chengmao Lin Research Updates

Neuropathy Core Microvascular Complications Diabetic Polyneuropathy Phenotyping Core Director, Eva L. Feldman, MD, PhD

2019 Publications

• Mitochondrial uncoupling has no effect on microvascular complications in type 2 . Hinder LM, Sas KM, O'Brien PD, Backus C, Kayampilly P, Hayes JM, Lin CM, Zhang H, Shanmugam S, Rumora AE, Abcouwer SF, Brosius FC 3rd, Pennathur S, Feldman EL. Sci Rep. 9(1):881, 2019.

• The divergent roles of dietary saturated and monounsaturated fatty acids on function in murine models of . Rumora AE, LoGrasso G, Hayes JM, Mendelson FE, Tabbey MA, Haidar JA, Lentz SI, Feldman EL. J Neurosci. 39(19):3770-3781, 2019.

• Integrated lipidomic and transcriptomic analyses identify altered nerve triglycerides in mouse models of prediabetes and type 2 diabetes O’Brien PD, Guo K, Eid SA, Rumora AE, Hinder LM, Hayes JM, Mendelson FE, Hur J, Feldman EL. Dis Model Mech. (under revision; see next slide) Diet Reversal Restores Peripheral Nerve Function

John Hayes Research Updates

Microbiome Core Aged mice have altered microbiota

• Mice from closed breeding colony at U of M • Mice were maintained under SCID housing • Compared microbiota of young (4‐6 week old) to old (22‐24 months old) via 16S analysis • Preparing grant application where we will associate metabolic/immunologic status

Vincent Young and Ray Yung Introducing the Mycobiome

The Microbiome Core will be introducing a new service: amplification and sequencing of the fungal ITS2. This Internally Transcribed Spacer region is between the nuclear genes coding for the 5.8S and 28S ribosomal RNAs. The ITS2 provides an inventory for fungi in much the same way that the 16S rRNA-encoding gene sequence is used for bacteria. So when fungi might be worth considering as a component of the mouse microbiome, we will offer a service to catalog the fungi present. Pricing will be the same as for bacterial 16S service.