As a pediatric neurosurgeon, Dr. Cheshier witnesses first hand the devastation that pediatric malignant brain tumors cause both the patients and families. The desire to help these people motivates him to conduct basic science research, with the goal of translating experiments into therapies.
Preclinical and Clinical Science: Dr. Cheshier’s laboratory performs highly sophisticated, pediatric specific, preclinical animal studies in order to eventually conduct a phase I clinical trial in children with malignant brain tumors including medulloblastoma, pediatric glioblastoma, and diffuse intrinsic pontine glioma. His group is utilizing a monoclonal antibody to stimulate immune cell macrophages to specifically target and remove these brain cancers with an emphasis on removal of the cancer stem cells.
This project is the culmination of at least three decades of basic science research at Stanford, starting with blood stem cells, and ending with a potential treatment for a wide range of cancers. Dr. Cheshier’s collaborators include basic scientist, physicians, and physician-scientists from across Lucile Packard Children’s Hospital at Stanford, and the School of Medicine. The group is taking the lead in attempting to bring this therapy to pediatric brain tumor patients upfront, rather than waiting for trials to be finished in adults, and then applying to pediatric patients in an “off label” manner.
Basic Neuro-Oncology Science: The laboratory utilizes novel combinations of cell surface molecules to isolate pure populations of normal neural stem cells/progenitors and determines their relationships to purified malignant-brain tumor stem cells/progenitors; including the stage of development malignant transformation occurs, as well as, the genetic and epigenetic events that differentiate cancer progenitors from their normal cellular counterparts. Dr. Cheshier’s current research emphasis is on adult and pediatric high-grade brain malignancies including medulloblastoma and glioblastoma. The group has also recently developed lenti-viral reporter constructs capable of marking cell populations on the basis of biochemical pathway activation such as Wnt, Notch, and SHh. The laboratory has developed robust in vitro methods to study the developmental fates of neural and cancer cells including single-cell analysis. Cancer cell populations, including cancer stem cells, are regularly analyzed by orthotropic xenograft transplantation into immune-compromised mice. Their hope is to gain insights into the events that transform normal stem cells into cancer stem cells which will lead to targeted therapies against these highly malignant cancers. This research is supported by the extensive infrastructure for translational research at Stanford University School of Medicine and Lucile Packard Children’s Hospital at Stanford. Dr. Cheshier and his collaborators are all fully dedicated to achieving their goals through continuous collaboration, novel research discoveries, and excellent patient care.