Activating Brain Tumor Stem Cells During Intra-operative Chemotherapy

Recently appointed to the neurosurgery staff at St. Michael’s Hospital, Sunit Das has a focused interest in malignant diseases of the brain, skull base and endoscopic neurosurgery. He will next add gamma knife radiosurgery to his skill set.

Sunit Das with his wife Pavani and their daughter Lakshmi

Sunit attended medical school at Northwestern University and then completed a neurosurgery residency there under Hunt Batjer, one of the great neurosurgical experts on vascular malformation. Batjer trained under the iconic Canadian neurosurgeon Charles Drake. Hunt is a Dallas Texan who creates an exceptionally calm atmosphere in the operating room. Hunt referred Sunit to his friend Jim Rutka during Sunit’s second year of neurosurgery residency. Jim has been a mentor ever since, writing supporting letters for every grant application, arranging for him to give talks and serve on committees to foster his career.

Sunit completed a PhD at NIH, focused on synaptic maturation and neural stem cell biology. “It was a fantastic place to learn, working with mentor Xuan Cheng and surrounded by spectacular scholars.”

In his laboratory in the MaRS building, Sunit he is working with glioma and glioblastoma stem cells. His focus is on signaling in the cell cycle, looking at signaling families at the EMT (epithelial mesenchyma transition). This is a pathway that has been actively and productively explored in breast cancer. The EMT interface maintains stem cells in a quiescent stage, but it is disrupted in gliomas and glioblastomas. The second pathway that he is studying is endothelial cellsignaling via prostacyclins. The prostacyclins maintain two niches in the brain where stem cells reside - in the subventricular area and the subgranulosa zone. Other signals push these cells toward differentiation, while vascular endothelial prostacyclins maintain them in equilibrium.

Sunit came to Toronto in order to combine clinical work with scientific work at a level that enables a surgeon scientist to keep his skills together. He will link clinical trials to laboratory investigations - for example, an RTOG (Radiation Therapy Oncology Group) trial working with 5 ALA, a compound that fluoresces when metabolically active cells break down. Resistance to chemotherapy is associated with stem cells. He hopes to be able to drive cells away from the stem cell phenotype to increase their sensitivity to chemotherapy and attack them with adjuvant treatment at the time of surgery. He will model his laboratory – based clinical work on the Brain Tumor Unit at the Hospital for Sick Children.

Sunit was born in Dhaka, Bangladesh, moved to New York city as an infant and subsequently moved to Detroit. He grew up as an immigrant Indian-American and as a scholar - athlete. He entered the honours program in English literature at the University of Michigan Ann Arbor and became interested in the life of the mind. He then studied political philosophy in graduate school at Harvard under Cornell West. He became interested in the philosophy of Locke, Wittgenstein and Heidegger. He considered pursuing philosophy or neuroscience and fortunately chose the latter. One of his surgical mentors was Mark Telemanti, a gifted surgical oncologist and highly praised and beloved clinician.

Sunit’s family includes his wife Pavani, a medical school classmate at Northwestern, and their two year old daughter Lakshmi. Pavani is a specialist in infectious disease, working at North York General and consulting for the Ontario Agency for Health Promotion. His dad is a pediatrician and his maternal grandfather was a military physician. Sunit runs and bikes and his wife skis. Sunit is currently reading the Anatomy of Influence by Harold Bloom, the dean of American literary critics and one of Sunit’s former teachers.

M.M.