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.

Selected Publications

Kauer TM, Figueiredo JL, Hingtgen S, Shah K. Encapsulated therapeutic stem cells implanted in the tumor resection cavity induce cell death in gliomas. Nat Neuroscience 2011 Dec 25, [ePub ahead of print]
 
Bagci-Onder, T., Wakimot, H., Cameron, C., Shah, K. A dual PI3K/mTOR inhibitor, PI-103, cooperates with stem cell delivered TRAIL in experimental glioma models. Cancer Research 2011, 71: 154-63
 
van Eeklen, M., Sasportas, L., Kasmieh, R., Yip, S., Figueiredo, J.L., Louis, D.N., Weissleder, W and Shah, K.,  Human stem cells expressing a novel TSP-1 variant have anti-angiogenic effect on brain tumors model; Oncogene 2010, 29:3185-95.
 
Hingtgen, S., Kasmieh, R., van de Water, J., Figueiredo, J.L., Weissleder, R and Shah, K.,  Creation and utilization of novel bifunctional theranostic molecules for anti-cancer therapy. Stem Cells 2010, 28:832-41.
 
Carney BJ, Shah K Migration and fate of therapeutic stem cells in different brain disease models. Neuroscience. 2011:ePub ahead of print
 
Shah, K.  Mesenchymal stem cells engineered for cancer therapy. Ad. Drug Delivery 2011; June 29