Max McGee National Research Center for Juvenile Diabetes
Max McGee, the famous Green Bay Packer, is best known in the sports world as the man who scored the first touchdown in Super Bowl I. But the generosity and dedication of McGee and his wife, Denise, to Children's Hospital and Health System is one for the record books, too.
Diabetes is prevalent in the McGee family. The McGees wanted a cure not just for their own son, but for all people living today with Type 1 diabetes. Thanks to their efforts, Children's Hospital and Health System established The Max McGee National Research Center for Juvenile Diabetes in 1999.
The center is one of a few in the world studying the role of genetics in diabetes. While diabetes is prevalent in some families, only 10 percent of newly diagnosed cases occur in families where that history exists.
Research in the Max McGee National Research Center for Juvenile Diabetes
Doctors and scientists do not yet understand the cause of Type 1 diabetes. Without understanding the cause, there can be no cure. We know that like cancer, high blood pressure and other diseases, there is a genetic component to Type 1 diabetes. Genetic does not necessarily mean hereditary. In the vast majority of cases, the diagnosis of Type 1 diabetes is a family first. In this case, genetic refers to how genes are "switched on" and "switched off" throughout a person's life. Genes are activated and deactivated at different times, and for different reasons. The questions are:
- Which genes play a role in diabetes?
- How do those genes function in a person without diabetes?
- How do those genes function in a person with diabetes?
- What makes the genes function differently in each case?
These are the questions posed by scientists at the Max McGee National Research Center for Juvenile Diabetes, a collaboration with the Medical College of Wisconsin.
Current research
Type 1 diabetes is a T-cell mediated disease that results in the destruction of insulin-producing beta cells of the pancreas, which leads to a lifelong dependence on insulin. The ongoing human genetics/immunology projects of the Max McGee Center support our overall research objective of finding ways to prevent and eventually cure Type 1 diabetes. We are working to understand the mechanisms for how and why Type 1 diabetes develops. We have uncovered increased death of protective T-cells in Type 1 diabetes as both a mechanism for the disease and as a biomarker. We also have unearthed a gene expression signature that implicates the IL-1 cytokine pathway as another contributor to Type 1 diabetes. We believe that the combination of cellular and cytokine biomarkers is going to be more powerful than a single marker alone. We now are working out the underlying pathogenesis for these observations using rat and mouse models.
We have enrolled more than 1,000 diabetic subjects, their families and controls through the Children's Hospital of Wisconsin Diabetes Program and from a parallel study in Finland. The aims are to find genetic markers that explain disease pathogenesis to help in future preventive and therapeutic strategies. We already have discovered a gene locus that could explain delayed onset of disease in the Finnish population.
Finally, we have used mathematical models to relate beta cell structure and function. We have obtained extra information from measurements of glucose and insulin levels and will use this data to predict poor beta cell function in someone likely to get Type 1 diabetes. The same modeling tools can be applied to subjects undergoing transplants in order to predict the lifespan of beta cells. By using a novel integrative modeling approach on high-throughput genomics data, we have been successful in locating two potentially new Type 1 diabetes genes that need to be verified in separate samples.
Leadership
Director
Faculty
Research scientists:
Sanja Milosavljevic, PhD
Research Scientist
(414) 456-4572
smilosav@mcw.edu
Jennifer Schiller, PhD
Research Scientist II
(414) 456-5661
jschille@mcw.edu
Postdoctoral staff:
Shouguo Gao, PhD
(414) 456-4982
sgao@mcw.edu
Srikanta Jana, PhD
(414) 456-4982
sjana@mcw.edu
Natalya Zinkevich, PhD
(414) 456-4070
nzinkevi@mcw.edu
Staff:
Joel Basken
John Blimke, PhD
Jeffery Bub
Sarah Ehlenbach
Rhonda Geoffrey
Parthav Jailwala, MS
Shuang Jia
Matt Klinker
Joanna Kramer
Marilyn Koppen
Ernie Luczkowski
Aparna Nittala, MS
Constance Ross
Jill Waukau
Karen Zeqiri
Publications
Alemzadeh R, Ellis J, Calhoun M, Kichler J. Predictors of Metabolic Control at One Year in a Population of Pediatric Patients with Type 2 Diabetes: A Retrospective Study. Journal of Pediatric Endocrinology and Metabolism. 2006; 19:1141-1149.
Alemzadeh R, Palma-Sisto, Holzum MK, Parton, E, Kichler J. Continuous Subcutaneous Insulin Infusion Attenuated Glycemic Instability in Preschool Children with Type 1 Diabetes Mellitus. Journal of Diabetes Science and Technology. 2007.
Alemzadeh R, Rising R, Lifshitz F. Childhood Obesity. In: Pediatric Endocrinology, fifth edition, Ed, Lifshitz F, Informa Healthcare USA, Inc., New York, 2007; 1:1-36.
Alemzadeh R, Wyatt DT. Diabetes Mellitus. In: Nelson Text Book of Pediatrics, 18th edition, Eds, Behrman, Kliegman, Jensen; W.B. Saunders, Philadelphia, PA; 2007; 590.
Eversten JM, Alemzadeh R. Increasing Ten-year Burden of Pediatric Type 1 Diabetes Mellitus in Southeastern Wisconsin: Relationship to Body Weight. Archives of Pediatrics and Adolescent Medicine. 2007.
Geoffrey R, Jia S, Kwitek AE, Woodliff J, Ghosh S, Lernmark A, Wang X, Hessner MJ. Evidence of a Functional Role for Mast Cells in the Development of Type 1 Diabetes Mellitus in the BioBreeding Rat. Journal of Immunology. 2006; 177(10):7275-7286.
Ghosh S, Schork N. Commentary on "Genetics of Type 2 Diabetes: The Study of Quantitative Traits." Commentaries on Perspectives in Diabetes. 2006; 213-214.
Glisic-Milosavljevic S, Waukau J, Jailwala P, Jana S, Khoo HJ, Albertz H, Woodliff J, Koppen M, Alemzadeh R, Hagopian W, Ghosh S. At-risk and Recent-onset Type 1 Diabetic Subjects have Increased Apoptosis in the CD4+CD25+high T-cell Fraction. PLoS ONE. 2007; 2:e146.
Guo SW, Magnuson VL, Schiller JJ, Wang X, Wu Y, Ghosh S. Meta-Analysis of Vitamin D Receptor Polymorphisms and Type 1 Diabetes: A HuGE Review of Genetic Association Studies. American Journal of Epidemiology. 2005 Oct. 15; 164(8):711-24.
Hains AA, Berlin KS, Davies WH, Smothers MK, Sato AF, Alemzadeh R. Attributions of Adolescents with Type 1 Diabetes Related to Performing Self-care around Friends and Peers: The Moderating Role of Friend Support. Journal of Pediatric Psychology. 2006; 10.1093/jpepsy/js1040.
Hains AA, Davies WH, Berlin KS, Walos JJ, Jandrisevits MD, Guillen A, Busetto G, Parton EA, Alemzadeh R. Aattributions of Adolescents with Type 1 Diabetes in Social Situations. Diabetes Care. 2006; 29:818-822.
Hessner MJ, Liang M, Kwitek AE. 2006. The Application of Microarray Analysis to Pediatric Diseases. Pediatric Clinics of North America. 53:579-590.
Hessner MJ, Xiang B, Jia S, Geoffrey R, Holmes S, Meyer L, Muheisen S, Wang X. 2006. Three-color cDNA Microarrays with Prehybridization Quality Control Yield Gene Expression Data Comparable to that of Commercial Platforms. Physiological Genomics. 25:166-78.
Jia S, Gao S, Hessner MJ, Wang X. Acquisition of Accurate Gene Expression Information from Microarray Measurements. In: Current Trends in Genetic Research. World Scientific Publishing. 2006.
Nittala A, Ghosh S, Stefanovski D, Bergman R, Wang X. Dimensional Analysis of MINMOD Leads to Definition of the Disposition Index and Improved Simulation Algorithm. Biomedical Engineering Online. 2006; 5(44):doi:10.1186/1475-925X-5-44.
Nolan K, Schiller J, Ghosh S, Magnuson V. Identification of a Novel HLA-DQB1 allele, DQB1*060403, by Sequence-based Typing. Tissue Antigens. 2006; 68(5):456-457.
Smith EM, Wang X, Littrell J, Eckert J, Cole R, Kissebah AH, Olivier M. Comparison of Linkage Disequilibrium Patterns between the HapMap CEPH Samples and a Family-based Cohort of Northern-European descent. Genomics. 2006; 88(4):407-14.
Wang X, He Z, Ghosh S. Investigation of the Age-at-onset Heterogeneity in Type 1 Diabetes through Mathematical Modeling. Mathematical Biosciences, 2006; 203(1):79-99.
Wang X, Hessner MJ. Quantitative Quality Control of Microarray Experiments: Toward Accurate Gene Expression Measurements. In Cambridge University Press: Gene Expression Profiling by Microarrays - Clinical Implications. Wolf-Karsten Hofmann (editor). 2006.
Wang X, Jia S, Meyer L, Xiang B, Chen LY, Jiang N, Moreno C, Jacob HJ, Ghosh S, Hessner MJ. Comprehensive Quality Control Utilizing the Prehybridization Third-dye Image Leads to Accurate Gene Expression Measurements by cDNA Microarrays. BMC Bioinformatics. 2006; 7(1):378.
Wang X, Jia S, Xiang B, Jiang N, Meyer L, Chen Li-Y, Moreno-Quinn C, Ghosh S, Jacob HJ, Hessner MJ. Accurate Gene Expression Measurements by cDNA Microarrays Utilizing TDAV. BMC Bioinformatics. 2006; 7(1):378.
Wu Y, Kajdacsy-Balla A, Strawn E, Basir G, Halverson Z, Jailwala, P, Wang Y, Wang X, Ghosh S, Guo S-W. Transcriptional Characterizations of Differences between Eutopic and Ectopic Endometrium. Endocrinology. 2006; 147:232-246. |
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