About the Lab
Our lab is focused on understanding the cellular and molecular mechanisms that regulate the recruitment and activation of immunosuppressive myeloid cells in solid tumors. Cancer immunotherapy has recently revolutionized the field of cancer therapy. Despite the tremendous clinical success of immunotherapy over other cancer treatments, this approach has shown benefit to only some of the patients, while a significant fraction of patients do not respond to this therapy. Immunosuppressive myeloid cells and macrophages secrete several cytokines to promote immunosuppression and to dampen anti-tumor immune responses which leads to failure of immunotherapy. Our lab uses genetic mouse models and human patient samples to investigate the interactions between immune cells and tumors. Currently, we are using transgenic mouse models of pancreatic ductal adenocarcinoma and neuroblastoma to study the functional role of these innate immune cells in modulating the tumor microenvironment.
Our lab has identified a novel macrophage autonomous pathway involving Rac2 and Syk kinase downstream of the provisional integrins, a4b1 and avb3 that controls immunosuppressive macrophage differentiation in tumor growth and metastasis. Our recent work has demonstrated Syk as a novel immuno-oncology target which plays a crucial role in the control of macrophage-mediated immune suppression and the inhibition of anti-tumor immunity in the lung carcinoma model. We have shown that genetic or pharmacologic inhibition of Syk and/or PI3Kgamma in macrophages promotes a proinflammatory macrophage phenotype, restores CD8+ T-cell activity, destabilizes HIF under hypoxia, and stimulates an antitumor immune response in various syngeneic mouse models.
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