51吃瓜黑料曝料

Ali Arbab, MD, PhD

Professor, Biochemistry and Molecular Biology

Member, Tumor Signaling and Angiogenesis

Research Summary

Our laboratory is devoted to determining the mechanisms of therapy resistance by focusing on the involvement of bone marrow-derived cells in modulating the tumor microenvironment (TME) and initiating tumor neovascularization in glioblastoma and breast cancer models. Transgenic, chimeric, and wild type (syngeneic and immunocompromised) animals are being used to determine the involvement of bone marrow cells in the TME. Our group documented that tumor-recruited bone marrow cells are a predominantly heterogeneous myeloid cell population that can predict therapeutic response in cancer. Therefore, we are using several strategies to target myeloid cells in the TME using nanonized drugs or engineered therapeutic exosomes to potentiate the anti-tumor effect of FDA-approved drugs in preclinical models of glioblastoma and breast cancer. Besides, our group has successfully tested the IV formulation of the new drug HET0016 for the treatment of glioblastoma and breast cancers.

In addition to the tumor cell-extrinsic mechanisms, tumor intrinsic mechanisms such as vascular mimicry are being actively investigated in our laboratory. Tumor cells, under the influence of therapeutic drugs and hypoxia, acquire endothelial cell-like characteristics through a mesenchymal cell state to enhance tumor vasculature and therapy resistance to cause a relapse. We have identified a possible pathway that governs the transdifferentiation of tumor cells to make their own blood-supplying channels in the case of AAT-induced hypoxia. Our group also identified that following anti-angiogenic treatment there is the nuclear translocation of VEGFR2 in glioma.