Current Research

Cancer Immunology: Our studies on cancer use spontaneous mouse lung and colon tumor models that were crossed onto mice deficient in BLT. BLT1 is an important mediator of host response to infection and immune surveillance of intestinal cancers. Our studies showed that exposure to crystalline silica, a common agent encountered in mining and other industries strongly promotes lung cancer and that absence of BLT1 protects mice from developing silicosis and reduces the lung cancer burden. Our observations in models of colon cancer suggest that absence of BLT1 reshapes the gut microbiome to promote colon cancer development. Absence of BLT1 was also found to significantly impair cytotoxic T-cell mediated anti-tumor immunity in intestinal tumors as well as in implantable melanoma. In this case mast mediated LTB₄ acts to recruit CD8⁺ T-cells and our current studies are aimed at understanding the mechanistic implications of these findings. We are currently testing whether ectopic expression of BLT1 improves homing of cytotoxic T cells in to tumors to enhance the efficasy of tumor immunotherapies.

Alzheimer's Disease: Our recent observations on mouse models of Alzheimer’s disease (AD) suggest a complex role for lipid mediators of inflammation and microbiota in promoting neurodegenerative disorders. We are working with 5XFAD and 3xTG models that are rederived as germ-free and crossed onto mice lacking distinct chemokine receptors including BLT1 and CCR2. We have generated gnotobiotic mice stably transferred with AD patient microbiome via FMT of germ-free 3xTG mice. We are using cellular immunology, spatial transcriptomics and metagenomics to identify the role specific bacteria in promoting and/or protecting from AD progression.