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Winter 2010 Newsletter

Message from the Director

The Administration Core coordinated the Center’s application to NIDDK in response to the American Recovery and Reinvestment Act of 2009 (ARRA). The MDRTC was awarded $200,000 in additonal Pilot and Feasibility (P/FS) funds and $200,000 for equipment in September 2009. We were also awarded an additonal $200,000 in P/FS funds in December 2009. This allowed us to fund five P/FS grants and three Diabetes Interdisciplinary Studies Program grants this year and will provide $450,000 for P/FS grants in the fall of 2010. For more information on the grants awarded see the section on Pilot and Feasibility Studies in this newsletter.

We plan to purchase a Multidetection Technology Analyzer for the Chemistry Laboratory and additional animal cages for the Animal Phenotyping Core with the funds made available from NIDDK. For more information on this equipment and your importance as MDRTC members see the section on Core Updates.

I would like to take this opportunity to introduce you to several new MDRTC members. Please join me in welcoming:

Malcolm J. Low, MD, PhD, Professor, Molecular & Integrative Physiology
Research Interests: Hypothalamic control of energy homeostasis; Neuropeptide gene expression; Neural circuits underlying food reward

Puneet Garg, MD, Lecturer, Internal Medicine – Nephrology
Research Interests: Molecular biology of Glomeular Slit Diaphragm, Vascular calcification in end stage renal disease, Hypertension

Wenjun Ju, PhD, Research Assistant Professor, Internal Medicine - Nephrology
Research Interests: Non-invasive biomarker identification, Pathomechanism study of biomarkers

Friedhelm Hildebrant, MD, Investigator, Howard Hughes Medical Institute, Professor of Pediatrics and Human Genetics
Research Interests: Gene identification in ciliopathies; Cystic kidney disease; Bardet-Biedl syndrome; Alstrom syndrome

Ernesto Bernal-Mizrachi, MD, Larry D. Soderquist Professor and Associate Professor of Internal Medicine
Research Interests: Beta cells biology; Islets; Pancreas development

Alla Karnovsky, PhD, Research Investigator, Center for Computational Medicine & Biology Research Interests: Systems Biology, Bioinformatics, Metabolomics

I would also like to remind you of the importance of citing the MDRTC in your publications when you have used MDRTC core resources. NIDDK is using the number of research papers citing the grant to evaluate diabetes centers. A national Diabetes Centers website was established which automatically retrieves publications from PubMed Central that contain the Center grant number (see article below). Currently, less than one-third of the publications supported by the MDRTC actually cite the MDRTC grant number in the Acknowledgements. We need to improve our reporting.

The following language should be used to recognize the MDRTC in publications:
“This work utilized ______Core(s) of the Michigan Diabetes Research and Training Center funded by DK020572 from the National Institute of Diabetes and Digestive and Kidney Diseases.”
OR

“This work was funded by a Pilot and Feasibility Study from the Michigan Diabetes Research and Training Center (DK020572 from the National Institute of Diabetes and Digestive and Kidney Diseases).”

Best wishes for the New Year,
Bill

MDRTC Core Updates

Chemistry Laboratory to purchase a Multidetection Technology Analyzer: Luminex xMap multiplex

Luminex analyzers allow for multiplex immunoassay, the determination of multiple analyses in a single reaction well. Multiplex immunoassay offers numerous advantages over other methodologies, including significant savings in time and cost when compared to ELISA technology. This system makes it possible to obtain and run a comprehensive line of validated reagents and services suited to the Luminex® xMAP® multiplex detection technology, including cytokines, chemokines, adipokines, and human and rodent endocrine hormones. This system offers the capability of doing multiple protein measurements off a single small volume blood sample, making it ideal for research studies involving rodent models of diabetes.

Animal Phenotyping Core to purchase Extension Cages to Upgrade CLAMS Unit

A major service of the Animal Phenotyping Core includes the analysis of rodent models of metabolic disease in a CLAMS apparatus; this instrument continuously assesses feeding, drinking, VO2, VCO2, and activity for the analysis of energy balance and metabolism. The Core has a single apparatus that can study 8 mice (or 4 rats) simultaneously. Since the average study requires 4 days in the device and demand is high, the current unit is oversubscribed and the machine is scheduled several months in advance. Requests for CLAMS analyses continue to increase. In order to increase throughput, the core will expand our current apparatus from 8 to 16 cages (for mice) and from 4 to 8 cages (for rats). This will effectively double the core’s capacity and increase the pace and number of animals the core is able to phenotype for MDRTC members.

Cell & Molecular Biology Core
Bacterial Artificial Chromosome Recombineering

The BAC Recombineering Core was fully operational as of October 2009. Bacterial Artificial Chromosomes (BACs) are plasmid-like constructs that can be grown in E. coli and that contain genomic DNA fragments of ~200 kb. BACs are commercially available that contain most of the genes from human, mouse and other species. These can be modified (“recombineered”) by insertion, deletion or point mutation, and can then be used as targeting vectors to modify endogenous genes in mice, or to produce transgenic mice. Thus, BACs can be used to create mouse models of human diseases and to make mice expressing reporter genes. Since BAC recombineering is technically demanding, the BAC Recombineering Core has been established.

This core is managed by Thom Saunders tsaunder@umich.edu and functionally is part of the Transgenic Animal Model Core. The MDRTC provides substantial support for the BAC Recombineering Core, therefore MDRTC members utilize its services at a significant discount. MDRTC investigators will be charged $500 for BAC recombineering (per construct), and $25 for BAC DNA purification including pulsed field gel verification of restriction enzyme fragments. The BAC Recombineering application is located on the MDRTC website at http://www.med.umich.edu/mdrtc/cores/MBCore/index.html and should be completed and sent to 2560 MSRB II, Box 0674.

Biostatistics and Economic Modeling Core:
New Disease Modeling Tools and a new version of the Michigan Model for Diabetes

A new addition to the MDRTC website is Disease Modeling software which should be of use to disease modelers and researchers who did not previously have modeling tools available. This is free software that can be downloaded under GPL license and allows simulation of diabetes disease progression. The user can create and modify disease models, include population covariates, define intervention rules, and apply cost and health utility estimates. The software includes a user Interface that simplifies the work.

This software was used to create a new and updated version of the Michigan Model for Diabetes. The new model was validated against published results from the United Kingdom Prospective Diabetes Study. This model is available as a file for download and after download can be used by the modeling software. The model is fully documented including the sources of information and results. Simulation results that validate the model against the UKPDS33 study are also available online.

The address of the web site is:
http://www.med.umich.edu/mdrtc/cores/DiseaseModel/

The website contains videos that explain the method used for disease modeling and also contains an online user manual for using the software. Future improvements will be published online and include improving the model and the software. The current focus is on improving the estimates used to model retinopathy and tools to estimate model parameters using data from multiple studies.

MDRTC Move to Brehm Center

The following MDRTC cores will be moving to the new Brehm Center located on Wall Street between February and April 2010:

Administration Core
Animal Phenotyping Core
Chemistry Laboratory
Morphology and Image Analysis Core

More information will be forthcoming regarding the dates and the relocation sites.

NIH-Sponsored Medical Student Training Program for Summer 2010

The Medical Student Summer Research Program in Diabetes is sponsored by the National Institutes of Health through the NIDDK and allows medical students to conduct research under the direction of an established scientist in the areas of diabetes, hormone action, physiology, islet cell biology, or obesity at one of 16 NIDDK-funded Diabetes and Endocrinology Research Centers (DERC) or Diabetes Research and Training Centers (DRTC). The medical students must work for 9-12 weeks (June-August 2010) with a mentor and are paid a stipend by NIH. Medical students must be between the first and second year or second and third year of medical school during the summer of 2010 to qualify for this program. The objectives of this program are to provide students the opportunity to conduct diabetes-related research and to gain an improved understanding of career opportunities in biomedical research.

If you know of a student who may be interested, please inform the student of this opportunity. More information and the application the students must complete by January 25, 2010 is located at http://medicalstudentdiabetesreseach.org/

The mentors for the 2009 MSTP program included John A. Williams, MD, PhD, Molecular & Integrative Physiology, Caroline Richardson, MD, Family Medicine, Amy Rothberg, MD, Internal Medicine, Metabolism, Endocrinology and Diabetes, and Peter Dempsey, PhD, Pediatrics and Communicable Diseases.

If you are interested in becoming a mentor for a medical student, please email Linda Potter at ldpotter@umich.edu to inform her of your interest and the type of research the medical student would participate in under your mentorship.

Pilot and Feasibility Grants

The MDRTC Grants Advisory Council met in November 2009 to review applications for P/FS grants from researchers across the University of Michigan. The goal of the grant program is to enable awardees to generate a sufficient body of preliminary information for a successful application for major research funding from the National Institutes of Health or other national granting agencies. During the 31-year history of the MDRTC, more than one-half of P/FS grants awarded have developed into extramurally-funded research programs.

The following researchers were awarded P/FS grants in 2009:
Pilot/Feasibility Study Grant Program Awardees

Diabetes Interdisciplinary Study Program (DISP) Awardees

Accolades to MDRTC Members

Internal Awards
Lori Isom, PhD, Director, Program in Biomedical Sciences and Professor, Department of Pharmacology
2009 University of Michigan Rackham Graduate School Distinguished Faculty Award

Robert W. Lash, MD, Professor of Internal Medicine
Kaiser- Permanente Award for Excellence in Clinical Teaching

Martin G. Myers, Jr., MD, PhD, Marilyn H. Vincent Professor in Diabetes Research, Associate Professor of Internal Medicine and Molecular & Integrative Physiology
Basic Science Research Award

Stephen J. Weiss, MD, E. Gifford and Love Barnett Upjohn Professor of Internal Medicine and Oncology, Professor of Internal Medicine, Research Professor, Life Sciences Institute
Distinguished Faculty Lectureship Award in Biomedical Research

John A. Williams, MD, PhD, Professor of Molecular & Integrative Physiology and Professor of Internal Medicine
2009 First Horace W. Davenport Collegiate Professor of Physiology

External Awards
Lori Isom, PhD, Director, Program in Biomedical Sciences and Professor, Department of Pharmacology
2009 Distinguished Alumni Lecturer, University of Washington, Department of Pharmacology

Ormond MacDougald, PhD, Professor of Molecular & Integrative Physiology and Professor of Internal Medicine
2009 Edictorial Boards of Journal of Biological Chemistry, Obesity

Linda Samuelson, PhD, Professor of Molecular & Integrative Physiology
2008-2011 American Physiological Society Councilor

Tae-Hwa Chun, MD, PhD, Assistant Professor of Internal Medicine
2008 Young Investigator Award American Society for Clinical Investigation.

Massimo (Max) T. Pietropaolo, MD, Professor of Pediatrics and Communicable Diseases
University of Perugia Medical School
Award for Career Achievements in Medicine

Dr. Massimo (Max) T. Pietropaolo, MD Professor of Pediatrics and Communicable Diseases, was appointed Chair of the NIH study section: Diabetes, Endocrinology and Metabolic Diseases B Subcommittee of the Diabetes and Digestive and Kidney Diseases Initial Review Group, NIDDK.

Victoria Hsiao, MD, PhD
2009 Lilly Endocrine Scholars Award

Martha Funnell, MS, RN, CDE
Chair, National Diabetes Education Program (NDEP)

Liangyou Rui, PhD, Associate Professor of Molecular & Integrative Physiology,
Star Reviewers for the Endocrinology and Metabolism Section of the American Journal of Physiology.

Winter Symposium

Please hold April 23 for the 2010 Winter Symposium to be held in conjunction with the Brehm Center dedication. Invited speakers will be Drs. Domenico Accili, Jeffrey Bluestone, Chris Rhodes, Matthias von Herrath and Matthias Hebrok. Further information will be sent out early in the new year.