Research
Our research objective is to define and prevent immune-mediated effector mechanisms involved in the destruction of insulin-producing pancreatic beta-cells in Type 1 diabetes (T1D) and islet transplantation. Specifically, we are interested in determining how oxidative stress can regulate innate and adaptive immune responses.
We previously demonstrated that non-obese diabetic (NOD) mice lacking the ability to generate NADPH oxidase-derived superoxide exhibited a significant delay in spontaneous, adoptive transfer and virus-accelerated T1D. Our research has shown a synergistic interaction between redox biology and dysregulated autoimmune responses, specifically, the activation of signaling pathways necessary to mature CD4+ and CD8+ T cell effector responses and promote inflammatory macrophage differentiation in T1D are redox-regulated.
Currently, we continue to characterize the redox dependency of antiviral responses following diabetogenic Coxsackievirus infections, the role of thiol-dependent signaling on autoreactive T cells, why genetic susceptibility genes influence autoimmunity and the efficacy of islet encapsulation to delay allo- and xenograft rejection in mouse models and human translational studies in T1D.
Current Research Projects
- Determine the role of mitochondrial fusion and fission on autoreactive CD4 T cell effector responses in Type 1 diabetes
- To define how single nucleotide polymorphisms in IFIH1contribute to Type 1 diabetes susceptibility and resistance in immune cells and beta-cells following Coxsackievirus infection
- To determine the role of redox signaling in immune cells and beta-cells during spontaneous Type 1 diabetes
- To assess the efficacy of islet encapsulation to delay islet allograft rejection and elicit localized immunosuppression following transplantation
Current Laboratory Funding
- R01 DK131716, NIH/NIDDK
Tse, HM (PI)
Islet encapsulation to elicit localized immunosuppression and immune modulation following transplantation, To determine if islet encapsulation with various immune modulators can delay islet graft rejection. - R01 DK127497, NIH/NIDDK
Tse, HM (PI)
Determining the mechanism of IFIH1 disease-associated variants on beta-cell and immune responses in Type 1 diabetes, To define how single nucleotide polymorphisms of IFIH1contribute to Type 1 diabetes susceptibility and resistance - R01 DK126456, NIH/NIDDK
Tse, HM (PI)
Beta-cell responses to oxidative stress and Type 1 diabetes, To determine the role of NADPH oxidase-derived superoxide on beta-cell function in Type 1 diabetes - 2208831 NSF
Tse, HM (Co-PI); Kharlampieva, E (Co-PI)
Reprogrammading redox-controlled innate and adaptive immune responses by antioxidant polymer microvesicles, To determine if autoimmune responses can be redox modulated by treatment with antioxidant polymer microvesicles containing autoantigenic peptides - R01 DK116875, NIH/NIDDK
Tse, HM (Co-I); Fraker, C (PI)
Optimizing cellular encapsulation to treat Type 1 Diabetes Mellitus: The role of antigen shedding and early macrophage responses, To characterize the role of macrophages and antigen shedding following islet transplantation - R01 DK132583, NIH/NIDDK
Tse, HM (Co-I); Piganelli, J (PI)
Examining the role of CVB in the generation of beta cell neoantigens and targeted approaches at therapeutic intervention, To determine if neoantigens are generated following Coxsackievirus infection - 3-SRA-2023-1392-S-B, JDRF
Tse, HM (Co-I); Soleimanpour, S. (PI)
Repurposing LRRK2 inhibitors for beta-cell protection in T1D, To assess the efficacy of LRRK2 inhibitors to delay autoimmune diabetes in the NOD mouse
Current Trainee Funding:
- T32 Cell, Molecular, and Developmental Biology (CMDB) (T32.GM008111) pre-doctoral trainee slot – Miranda Chávez (Brad Yoder, PI)
- 1F31GM150237-01A1
Burnette, KaLia (PI)
Identifying Gestational-induced Changes in Islet Macrophages as a Potential Target for Beta-cell Expansion