The Neuro-Oncology Branch (NOB) has developed robust scientific programs addressing critical areas of brain and spine cancer research. Our investigators translate laboratory findings into clinical trials that are designed to assess whether a treatment is working and what impact it has on the patient. Each of our research programs has the same goal: to improve brain and spine cancer patient care and outcomes.
Clinical Research Program
Led by Mark Gilbert, M.D., and Terri Armstrong, Ph.D., this program encompasses a growing portfolio of therapeutic clinical trials to treat brain and spine cancer patients, as well as a series of complementary non-therapeutic studies. The NOB's extensive clinical research infrastructure enables our investigators to launch critical studies, including Phase 0 studies using both microdialysis techniques and post-treatment tumor resection to determine tumor drug delivery; Phase I studies with pharmacokinetics and pharmacodynamics; and single arm Phase II studies. Larger scale clinical trials are being conducted through the Brain Tumor Trials Collaborative (BTTC) and NCI-CONNECT (Comprehensive Oncology Network Evaluating Rare CNS Tumors), both led by the NOB. Patient outcomes measures are integrated into each clinical trial, complementing ongoing work in the NOB's Patient Outcomes Program.
Patient Outcomes Research Program
Led by Terri Armstrong, Ph.D., this program implements outcomes measures that assess brain and spine cancer patients over the course of their disease. This research utilizes longitudinal data from the Natural History Study, patient reported outcomes measures to learn cancer risk information, and biologic samples including germline DNA for single nucleotide polymorphisms. Dr. Armstrong is also developing preclinical models for treatment-related toxicities including radiation-induced somnolence, which may have an association with polymorphisms of select CLOCK genes.
Translational Research Program
Led by Jing Wu, M.D., Ph.D., this program develops brain and spine cancer clinical trials based on strong preclinical science and rationale. For example, Dr. Wu's studies with the multi-kinase inhibitor TG02 have led to the creation of a successful Phase I trial. The Translational Research Program is also investigating the malignant transformation and hypermutation that occurs in a subset of patients harboring IDH-mutated gliomas. This translational research complements the Cancer Metabolism Research Program, translating preclinical models and imaging biomarkers into clinical trials.
Immunology Research Program
Initially led by Mark Gilbert, M.D., and called the Translational Immunology Research Program, this program has since transitioned its leadership to Masaki Terabe, Ph.D., who runs the Basic Immunology Research Program. The team is now focused on various aspects of translational and basic immunology, such as examining the biology of natural killer T (NKT) cells that serve as potent mediators of the immune response in brain and spine cancers. Other research topics include:
- Techniques to assess the immune phenotype of brain and spine tumors
- Patient immunocompetence and metrics of peripheral response to immune modulators
- The impact of treatment agents such as chemotherapy and corticosteroids on immune reactivity
- A fundamental understanding of the mediators of an effective immune response, such as immune cell trafficking
- Chemokine production in the tumor microenvironment
Cancer Stem Cell Biology Research Program
Led by Zhengping Zhuang, M.D., Ph.D., this program was founded on Dr. Zhuang's longstanding interest and expertise in evaluating hypoxia and pseudohypoxia, as well as the role of HIF2α abnormalities in brain and spine cancer biology. The Cancer Stem Cell Biology Program's ongoing research is focused on understanding the functional impact of genetic changes that may uncover early disease states and potential therapeutic opportunities.
Molecular and Cell Biology Research Program
Led by Chunzhang Yang, Ph.D., this program investigates the biological impacts of cancer-associated IDH mutations to uncover selective vulnerabilities in brain and spine cancers. Dr. Yang's research has demonstrated that DNA repair pathways are compromised in IDH-mutated cells, and that Nrf2-mediated metabolic pathways—such as glutathione de novo synthesis—support these cells by relieving metabolic stress and oxidative damage. These studies may have a direct link to clinical studies, as researchers in the Translational Research Program are developing a robust therapeutic program for patients with IDH-mutated tumors.
Cancer Metabolism Research Program
Led by Mioara Larion, Ph.D., this program studies the effects that IDH mutations have on tumor metabolism, with a particular focus on gliomas. Specifically, Dr. Larion is exploring the impact that IDH mutations have on cellular requirements for carbon sources; lipid metabolism at the molecular, organelle, and cellular levels; and the preclinical development of hyperpolarized MRI using 13C substrates to measure in vitro metabolic flux. Her research complements the cell biology-focused Molecular and Cell Biology Program and the clinical research on IDH-mutant tumors performed in the Translational Research Program.