The primary goal of our research is to understand molecular mechanisms regulating tumor growth, inflammation and metastasis. Our laboratory is focused on the study of signaling cascades that regulate recruitment and activation of immunosuppressive macrophages in the tumor microenvironment during tumor progression. In this regard, we have defined a novel mechanism by which signals transmitted from the extracellular matrix via the a4b1 integrin and MCSF receptor lead to the activation of Rac2 and Syk which potentially regulate protumerogeni macrophage differentiation and mediates immunosuppression and tumor growth in various solid tumors. An important recent discovery from this study is the identification of Syk kinase and Rac2 as novel targets in macrophages which control innate and adaptive antitumor immune responses during tumor growth. We are now investigating 1) the mechanisms which promote the recruitment of macrophages in MYCN amplified and non-MYCN amplified neuroblastoma tumors 2) if macrophage targeted therapies in combination with immune checkpoint inhibitors or radiotherapy can improve survival of patients in neuroblastoma. In parallel 3) we are exploring the role of Syk kinase in the progression of pancreatic carcinoma.