Khalid Shah, PhD
Harvard Medical School
Successful treatment of brain tumors remains one of the greatest challenges in oncology. The recognition that different stem cell types, including neural stem cells (NSCs) can integrate appropriately throughout the mammalian brain following transplantation has unveiled new possibilities for their use in neural transplantation. Our laboratory has shown that different stem cell types home to sites of cerebral pathology and thus can be armed with therapeutic transgenes, a strategy that can be used to inhibit tumor growth by targeting angiogenesis or selectively inducing apoptosis in proliferating tumor cells in the brain.
Our research is based on simultaneously targeting cell death and proliferation pathways in an effort to eradicate gliomas using therapeutically engineered stem cells, microRNA inhibitors and shRNAs. We have engineered different stem cells types (i) to secrete therapeutic protein, S-TRAIL (secreted Tumor necrosis factor receptor-apoptosis inducing ligand) to specifically induce apoptosis in tumor cells and anti-angiogenic TSP-1 (thrombospondin-1) to inhibit tumor angiogenesis. These stem cells are then used to populate primary tumors and their secondary micro-invasive deposits in the brain. Inherently linked to the brain tumor therapy paradigm, we employ fluorescent/bioluminescent imaging markers and optical imaging techniques to track NSC, image apoptosis and changes in tumor volumes in real time in vivo. We also explore the use of microRNAs inhibitors to target brain tumor specific microRNAs and shRNAs to target proteins specifically over-expressed in brain tumors in combination with therapeutic stem cells.