Research in our group is focused on understanding the mechanisms that lead to the loss of immune tolerance in autoimmune diseases. We are particularly interested in Type 1 Diabetes (T1D), the form of diabetes that results from autoimmune destruction of pancreatic insulin-producing beta cells. We are combining directed differentiation of human pluripotent stem cells into cell types relevant to T1D with genome engineering to model the human disease in vitro and in humanized mouse models. Our innovative research thus leverage a unique combination of stem cell differentiation, beta cell biology, and immunology expertise to study human autoimmune diseases.

The main areas of research in our laboratory include:

1. Modeling Autoimmune Pathogenesis and Beta Cell Destruction by T1D Immune Systems - Understanding the initiation and progression of human T1D has been hampered by the lack of appropriate models that can reproduce the complexity and heterogeneity of the disease. One of our projects is thus focused on creating new state of the art humanized models that incorporate stem cell-derived derivatives relevant to T1D, including thymic epithelial cells, which are critical to the development of new self-tolerant T cells, immune cells, and pancreatic beta cells.

2. Creation of immune evasive stem cell-derived beta cells for the treatment of diabetes - Successful clinical translation of stem cell therapies requires overcoming the major roadblock of immune rejection due to alloimmune responses and islet-specific autoimmune responses against transplanted beta cells present in patients with T1D. We are taking advantage of recent advances in genetic engineering methods to create immune evasive stem cell grafts, potentially allowing their survival in the absence of long-term immunosuppression. This work has led to the establishment of multiple interdisciplinary collaborations with researchers at UCSF and other institutions.

3. Development and education of human T cells - Our lab is generating thymic epithelial cells and immune cells from human pluripotent stem cells to study and manipulate immune tolerance. We have established a thymic organoid system and are using genetic engineering tools to better understand how specific genes affect thymic function. Overall, this work provides important insights into how the human thymus develops and functions and will further advance our understanding of immune tolerance defects in the context of human autoimmune diseases.