About 30,000 new patients are diagnosed each year with malignant tumor lesions in the brain, and most of these lesions remain untreated due to the complexity of the brain thereby effecting the quality of life for patients. Dr. Khalid Shah, of Massachusetts General Hospital and Harvard Medical School, focuses on the advancement of novel promising therapies for primary tumors in the brain as well as highly metastatic forms of tumors from the breast, lung, and melanomas that find their way to the brain. One major reason for the failure of numerous drugs to treat the tumors in the brain is the blood-brain-barrier that protects the entry of certain substances into the brain. Dr. Shah’s strategy to overcome this hurdle is to use stem cells that locally deliver certain substances into the brain or introduce the therapeutics via alternate routes that bypass the blood-brain-barrier. The development of these therapeutic interventions is essential for improving the overall survival of patients dealing with these deadly conditions.

Dr. Shah’s team capitalizes on their unique expertise in interdisciplinary research spanning stem cell and tumor cell biology, genetic engineering, and molecular imaging as well as their proven abilities to synthesize new insights from disparate fields, to lead interdisciplinary teams into new territory. In addition, while Dr. Shah’s research is deeply fundamental, there is always a translational aspect connected to it. As the leading cause of cancer-related deaths in children; second leading cause of cancer-related deaths in males ages 20-39; and the fifth leading cause of cancer-related deaths in females ages 20-39, the therapeutic options Dr. Shah and his team are developing will provide innovative and targeted therapies that are safe and effective to treat the large incidence of tumors.

Current research includes:

• Clinically relevant Mouse Tumor Models: Dr. Shah’s team has created mouse models that replicate the clinical settings of  primary (nodular and invasive) brain tumors and are currently creating metastatic brain tumor models from patient derived tumor cells.

• Tumor Specific Therapeutic Agents: Dr. Shah’s team is focused on engineering stem cells that release tumor specific therapeutic proteins such as death receptor targeting TRAIL, EGFR targeting nanobody (ENb); the fusion of ENb-TRAIL targeting tumor cells and TSP-1 targeting CD36 receptor on tumor associated endothelial cells; tumor specific toxin, pseudomonas exotoxin (PE) and novel oncolytic herpes virus (oHSV) targeting both cell death and proliferation specifically in tumor cells.

• Testing therapeutic efficacy of stem cell delivered therapeutics in clinically translatable models of primary, recurrent and metastatic brain tumors that mimic the clinical scenario of brain tumor aggressiveness, invasion, metastasis and resection.

• Non-invasive imaging techniques: Dr. Shah’s team utilizes non-invasive imaging techniques to follow the fate of tumors and therapeutic cells.