Our Research
Quantitative Proteomics
We have employed stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics to identify the proteins that are most abundantly expressed in the four molecular subtypes of medulloblastoma. We are now undertaking targeted CRISPR screening to validate these overexpressed proteins and determine which are essential for medulloblastoma cell survival. We will then evaluate the function of these essential proteins and determine their fitness as candidate drug targets.
Proteogenomic Discovery of Tumor-Specific Peptides as T cell Immunotherapy Targets
We have developed a proteogenomic pipeline employing DNA and RNA sequencing and mass spectrometry to identify peptides that are unique to tumor cells and expressed by no normal cells in the body. We are using these peptides to select and expand autologous T cells in order to develop a personalized immunotherapy.
Tumor-Specific Peptides as Cerebrospinal Fluid Biomarkers
We are measuring protegenomically identified, tumor-specific peptides in the cerebrospinal fluid of children with brain tumors in order to develop personalized peptide biomarker assays. These have the potential to monitor the effectiveness of therapy and detect tumor recurrence at the molecular level.
Methylation-Based Liquid Biopsy
Tumor DNA carries markings called methylation in specific locations. We are developing the means to identify these tumor markers in free-floating, cell-free DNA from cerebrospinal fluid. The goal is to create a marker capable of detecting the presence of tumor with greater sensitivity than magnetic resonance imaging (MRI).
Microsatellite-Based Cancer Predisposition
Small areas of repeated DNA sequence called microsatellites occur throughout the genome. The number of repeats varies from individual to individual. The sequence of these repeats can affect nearby genes and are nonrandomly associated with the occurrence of specific diseases. We have identified a signature set of microsatellites capable of differentiating healthy control subjects from children with medulloblastoma. We are now expanding this work to include a number of other pediatric brain tumors.