Glioblastoma is a brain cancer that is posing a formidable challenge to clinicians, researchers and patients because of its difficulty to treat. The culprit may be so-called glioblastoma stem cells—cancer stem cells identified in glioblastoma—that, despite being a minor population of cancer cells drive tumor progression, resist therapy and cause relapse. The goal of Dr. Wakimoto’s research is to develop novel therapeutic strategies for glioblastoma through a better understanding of the biological and molecular characteristics of glioblastoma stem cells that are likely associated with the unfavorable outcome of this brain cancer. Although efforts are directed at conducting laboratory studies of glioblastoma cancer cells using molecular, cellular and disease modeling approaches, emphasis is put on how to translate the leading-edge findings in the lab into better patient care in the clinic.
The Brain Tumor Stem Cell Lab (the Wakimoto Lab) has been successful in establishing more than 30 cultures of glioblastoma stem cells from patients that serve as a powerful tool to investigate how glioblastoma cancer cells proliferate, invade into the normal brain, and survive a variety of therapeutic agents such as anti-cancer drugs. These studies will lead to the development of new therapies that are effective at eradicating glioblastoma stem cells and can ultimately improve the lives of patients.
Characterizing glioblastoma stem cells
One of the main research focuses of the Brain Tumor Stem Cell Lab (Wakimoto Lab) is to characterize glioblastoma stem cells isolated from patient tumors. We are extensively establishing glioblastoma stem cells that grow in culture and testing their ability to form experimental brain tumors in mice. Our research shows that the capability of glioblastoma stem cells to migrate and invade through the brain varies greatly between patients. We are interested in identifying the molecular mechanisms that control tumor invasiveness. These studies are being conducted in close collaboration with the laboratories of Drs. Martuza, Rabkin, Curry, Cahill, Batchelor and Chi at Massachusetts General Hospital.
Glioblastoma stem cells are considered resistant to therapy such as chemotherapeutic drugs, but our research suggests that this is not always the case. Using glioblastoma stem cells as a unique model system that preserves patient-specific disease characteristics, we are evaluating the efficacy of therapeutic agents that include oncolytic herpes simplex virus -1 (in collaboration with the Martuza and Rabkin laboratories) and novel molecular targeting agents (in collaboration with the Batchelor and Chi Laboratories), and trying to discover molecular signatures of cells that help predict effectiveness for such treatment. Working closely with the Shah Laboratory of Radiology at Mass General, we are conducting research that harnesses normal stem cells to deliver therapeutic viruses to glioblastoma in the brain.
Cancer recurrence after surgery, radiation and chemotherapy is a serious issue that makes the management of glioblastoma difficult. We are trying to understand the role glioblastoma stem cells play in the relapse of the tumor. Our approach to this task is to establish glioblastoma stem cells from tumors both before and after therapy, and compare the two stem cells through analysis of their molecular and biological characteristics.
Taking advantage of the rich scientific environment at Mass General, the Brain Tumor Stem Cell Lab (Wakimoto Lab) works closely with the laboratories of Drs. Martuza, Rabkin, Curry, Cahill, Batchelor, Chi, Bernstein, Mohapatra, Iafrate and Shah. We are part of the Molecular Neurosurgery Lab and the Brain Tumor Research Center.