Neuro-Oncology Lab - Genetics of Brain Tumors
Our research activity is aimed at the identification of the genetic and epigenetic mechanisms associated with mesenchymal transformation in glioblastoma mulitforme (GBM). In addition, we are interested in understanding and characterizing the molecular mechanisms which underline these events. Our work aims to translate to the clinic. Our focus lies on the deregulation of signaling pathways that result in tumorigenesis and treatment resistance. We combine transcriptional, genomic and epigenomic analysis from patient tumor samples with both in vitro and in vivo models to identify new therapeutic strategies. We also aim to use tumor profiling and genomic analyses to benefit the patient in providing prognostic information and adding in therapeutic decision-making.
Brain tumors are highly complex, individual tumors, which require tailored treatment. However, to this date, therapeutic decision-making for brain tumor patients, such as patient enrollment into distinct clinical trials, is predominantly not based on the individual molecular makeup of a brain tumor disease but rather done by molding patients into risk groups inherently created by imprecise clinical and end-stage morphological measures.
Tumor profiling can expose the presence or absence of distinct disease-associated targets that may guide therapy. In addition, the ability of such profiles to estimate individual patient risk represents a major advantage relative to risk grouping of patient populations who share similar clinico-pathologic disease characteristics. Molecular profiles thus lend themselves to assist in difficult clinical decision-making.
Our laboratory is interested in "holistic" (genome-wide) molecular profiling strategies as well as "focused" strategies that utilize innovative and early phase biomarker assays to generate a unique "profile" for a brain tumor disease that provides insights into the prognosis and/or the most appropriate therapeutic regimen for any single patient.
Holistic analytic approach
As opposed to other genome-wide profiling efforts, which primarily aim at identifying predictive/ prognostic metagene predictor sets without looking at underlying mechanisms, our approach examines genome-wide profiles through the viewpoint of larger molecular pathways and networks rather than a gene-by-gene basis. They can also assess established resistance pathways/networks to predict a patient’s response to contemporary treatment and to guide tailoring treatment based on mechanisms that target critical molecular pathways.
Focused Analytic Approach
Focused target screens complement the holistic approach in that they assess specific members of molecular pathways/networks deemed to critically determine their status at the protein level. For protein analysis, we are utilizing novel assay technology that combines the strengths of both protein recognition and nucleic acid chemistry to result in a technology that is able to detect minute amounts of protein alone or in complex in as few as 10,000 brain tumor cells, easily attainable from a small stereotactic biopsy core. This methodology helps us establishing predictive tests that assist therapy decisions.