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Research Division Faculty



Maki Nakayama, MD, PhD
Assistant Professor, Department of Pediatrics
Assistant Professor, Integrated Department of Immunology

University of Colorado School of Medicine

Barbara Davis Center for Diabetes

BioSketch

Our laboratory focuses on the mechanism how anti-islet autoimmunity causing type 1 diabetes is initiated.  We approach this question from an aspect of autoantigens that are primarily targeted by autoreactive T cells and could be essential for the development of type 1 diabetes. We discovered that NOD mice (a mouse model spontaneously developing type 1 diabetes) lacking the insulin B chain 9-23 amino acid peptide (insulin B:9-23) sequence are protected from diabetes development (Nature 2005) and that expressing this particular insulin sequence in pancreatic islets triggers anti-islet autoimmunity (JCI 2007). These findings strongly suggest that the insulin B:9-23 peptide is an essential antigen for the development of type 1 diabetes in the NOD mouse model. Recently, our focus has moved to identifying and qualifying specific T cell receptor (TCR) sequences that recognize the insulin B:9-23 peptide and may initiate the development of anti-islet autoimmunity. We found that TCRs containing a specific Vgene called "TRAV5D-4" are sufficient to induce anti-insulin autoimmunity (Diabetes 2012). In addition, we have established a method to obtain and analyze millions of TCR sequences using the high-throughput technology. Utilizing this technique, we demonstrated that there is significant accumulation of TCRs containing the TRAV5D-4 Vgene in pancreatic islets of adult NOD mice. We are currently pursuing the role of T cells expressing TRAV5D-4 TCRs for the recognition of the insulin B:9-23 and for the development of type 1 diabetes. Targeting T cells expressing TRAV5D-4 TCRs may provide us an opportunity to develop antigen-based immunotherapy. To translate our findings in the NOD mouse model to human type 1 diabetes, we are investigating TCR repertoires in pancreas of patients having type 1 diabetes as well. Our ultimate goal is to identify target antigens of TCRs infiltrating pancreatic islets of patients having type 1 diabetes and to illustrate the mechanism how autoreactive T cells targeting such antigens are induced to destroy pancreatic beta cells and to cause type 1 diabetes. We believe that our findings will lead us to develop robust antigen-based immunotherapy to prevent and cure type 1 diabetes. 

Professional Research Assistant: Laurie Landry, PhD

Postdoctoral Fellow: Melanie Stumpf, PhD

Publications list:
http://www.ncbi.nlm.nih.gov/pubmed/?term=Nakayama+Maki

To access a more complete listing of publications, please go to PubMed http://www.ncbi.nlm.nih.gov/PubMed/ and use the search term Barbara Davis Center for Childhood Diabetes or enter individual author names.
Please direct inquiries to specific e-mail addresses listed within individual entries. For all other general Research inquiries, please contact:Kathryn Gray