Understanding molecular mechanisms of tumor growth and metastasis
The primary goal of our research is to understand molecular mechanisms regulating tumor growth, inflammation and metastasis. Our laboratory has longstanding focus on studying signaling cascades that regulate recruitment and activation of immunosuppressive macrophages in the tumor microenvironment during tumor progression. Our lab has 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 protumerogenic 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 controls stabilization of hypoxia inducible factor to regulate innate and adaptive antitumor immune responses during tumor growth.
a4b1-Syk-Rac2 Signaling axis controls immunosuppressive differentiation of macrophages to promote tumor growth, immunosupression and metastasis.
Developing novel immune therapies for neuroblastoma
Neuroblastoma is an extremely heterogeneous pediatric tumor that arises from neural crest and progression of this tumor is associated with infiltration of immunosupressive myeloid cells that foster tumor growth and metastasis. How these myeloid cells are recruited and activated in MYCN amplified and non-MYCN amplified pediatric neuroblastoma (NB) tumors is not well understood. Our studies have shown that myeloid cells recruited in neuroblastoma tumors express have levels of BTK and SYK and targeting these kinases can reverse myeloid-mediated immunosupression and can enhance immunotherapy in mouse model of neuroblastoma. We are currently investigating if these myeloid-targeted therapies can combine with immunotherapy and or radiotherapy to improve survival of patients with neuroblastoma.