Defining the roles of RIPK1 and RIPK3 in emergency hematopoiesisDescription of Major Goals
The major goal of this project is to understand how the negative regulation of necroptosis by RIPK1 and the positive regulation of necroptosis by RIPK3 affects hematopoieiss at steady state and following transplantation and infection. Aim 1b and Aim 3a have some overlap with this application.
Gene editing in ALL to promote immunomodulatory forms of lytic cell deathDescription of Major Goals
We propose to use CRISPR-Cas9 gene editing to eliminate RIPK1 (a negative regulator of necroptosis), as well as pharmacological approaches to access the necroptosis cascade. This research investigates the effects of necroptosis on leukemogenesis.
Gene editing in T cell leukemia to promote immunomodulatory forms of deathDescription of Major Goals
This research proposal will combine a panel of SMAC mimetics to increase the immunogenicity of cancer cell death and a panel of antibodies to suppress immune checkpoints in T cells to promote anti-tumor immunity. There is no overlap with this application.
Non-apoptotic death of neutrophils and eosinophils drives allergic asthmaDescription of Major Goals
The major goal of this research is to understand how neutrophil lifespan is affected in the setting of asthma and pulmonary infection, and the role of immunomodulatory forms of cell death. There is no overlap with this application.