Project: 

Humanized Mouse Avatars for T1D

►Where are you from originally, and where did you go to school?

University of Iowa

►What is your current position?

Professor, Co-Director of the UMass Diabetes Center of Excellence

►What is the “Big Picture” of what you study?

It is difficult to identify the mechanisms the cause of type 1 diabetes due to the inaccessibility of the target tissue and because most patients must be analyzed long after initiation of the autoimmune attack. Our lack of understanding of the key molecules and cells mediating the initiation and progression of human T1D may well underlie the paucity of significant new therapeutic interventions. We propose to use novel immunodeficient mice as recipients of three key cell types derived from human iPS cells (SC): hematopoietic stem cells (HSC) that will generate immune systems, thymic epithelial cells (TEC), and β-cells, all integral to the pathology of T1D. These cells will be derived through the use of directed differentiation and reprogramming strategies. Differentiated β-cells, TECs, and immune cells derived from T1D donors will be co-transplanted into our novel immunodeficieint mice that are specifically optimized to enhance SC-β cell, SC-HSC, and SC-TEC cell engraftment and function allowing reconstitution of an individual patient’s disease in an animal model. These new models of human diabetes will permit detailed observation, manipulation, and analysis of T1D, enabling us to determine the cells and antigens that initiate T1D, drive disease progression and mediate beta cell destruction. Critical to the success of this project is the collaborative team of scientists that have the expertise required to accomplish this.

► What do you hope to achieve with your research?

We hope to identify underlying mechanisms of T1D so we can develop approaches to prevent or cure the disease.