Harvard Catalyst Profiles

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Fatma Dogan, Ph.D.


Available: 12/01/22, Expires: 01/01/25

Type 1 diabetes (T1D) is a chronic and currently incurable disease in which insulin-producing beta cells within islets of the pancreas are destroyed by the immune system. Replacement of beta cells by islet transplantation has proven successful in providing a functional cure for T1D. However, the concomitant requirement for lifelong immunosuppression to protect the transplanted cells from allo- and/or autoimmune-mediated rejection and the scarcity of functional donor islets for transplantation are major limitations to this treatment. With the advent of protocols to generate insulin-producing cells from human pluripotent stem cells in scalable quantities in vitro, the requirement for chronic immunosuppression will remain the biggest hurdle in beta-cell replacement by islet transplantation. Chronic systemic immunosuppression predisposes patients to infection, organ damage, and cancer development. Thus, a strategy that can eliminate the need for immunosuppression and prevent allo-islet rejection could pave the way for widespread islet transplantation as a functional cure for T1D. In this project, we propose to test in mice two complimentary approaches to achieve this via co-delivery of both CXCL12 and Fas-ligand (Fas-L) with allogenic donor murine or human islets in mouse and humanized murine models of T1D. These two approaches have independently been shown in both small and large animal models of diabetes to protect and support the function of transplanted islets via different mechanisms. Therefore, we combined CXCL12/FasL approach could abrogate both the need for either microencapsulation of the transplanted beta cells or islets and any additional level of systemic immune suppression. We would like to see curious, attentive and skilled participants to our collaborative project in Poznansky lab. We will expect full time attendance to conduct the work and attend project meetings. We are giving opportunity to experience the wet lab, learn experiment design and handle mice study in collaborative environment. We will also have other interesting projects running in our lab related to T1D. Students are also welcomed to contribute and be part of hypothesis-based other projects as well.

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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.