Multi-Omics to Identify Novel Therapeutic Targets in Eye and Brain Tumors

Our laboratory utilizes multi-omics approaches to identify novel therapeutic targets in eye and brain tumors. Our studies identify signaling pathways cancer cells rely on for growth and survival and distinguishes cancer cells from normal human cells.

Metabolomics to identify therapeutic vulnerabilities in eye and brain tumors: Our laboratory completes stable isotope resolved metabolomics studies in flank and orthotopic brain tumors to identify metabolic dependencies modeled in an in vivo tumor microenvironment. These studies have uncovered metabolic dependencies in MYC-expressing medulloblastoma and atypical teratoid/rhabdoid tumors on glutamine metabolism for growth and survival. These studies have also shown that inhibiting glutamine metabolism depletes the anti-oxidant glutathione and makes cancer cells more sensitive to platinum chemotherapies. In addition, inhibiting glutamine metabolism depletes metabolic co-factors required to maintain tumor’s abnormal epigenetic landscape, known to transform and drive the aggressive growth of these tumors.
Phosphoproteomics to identify therapeutic vulnerabilities in eye and brain tumors: Phosphoproteomics is an extremely powerful research technique that can identify changes in the expression and modification of tens of thousands of proteins in one study. We have used this approach to understand how medications combine to impact important signaling pathways and to identify pathways of therapy resistance.

Pre-Clinical Drug Testing to Improve Therapies for Eye and Brain Tumors

We complete extensive pre-clinical drug testing to identify novel therapeutics to improve treatments for eye and brain tumors. These studies are focused on translating novel therapies into new clinical trials aimed at improving survival and reducing side effects of therapy. We complete rigorous pre-clinical studies including formal synergy studies, pharmacokinetics and pharmacodynamics evaluations, toxicity profiling, and survival studies in multiple orthotopic tumor models to ensure the successful translation into new and successful clinical trials. We also work to develop the correlative studies that help ensure that the clinical trial will improve our understanding of tumor biology and response to therapeutics so clinical trials continue to build on these developments.

Pre-Clinical drug testing in eye and brain tumors: Our extensive pre-clinical drug testing includes formal synergy testing of drug combinations in vitro. However, we focus many of our studies in orthotopic xenograft tumor to ensure we study tumors and the impact of medication in the proper tumor micro-environment. These studies include bioluminescence imaging and survival studies and shown here but also includes extensive toxicity profiling and pharmacokinetic and pharmacodynamics evaluations of medications.

Tumor Modeling to Improve our Understand of Eye and Brain Tumors

Our understanding of eye and brain tumors is only as good as the models we use to study them. We have assembled one of the largest collections of eye and brain tumor human-derived cell models and patient derived xenograft models. We have also developed new techniques to improve the number of successful models developed from surgical biopsies and autopsy specimesn. In addition we have developed zebra fish models to better image and test therapeutics in eye and brain tumors.

Conditional reprogramming culture media: Our laboratory has developed new techniques to facilitate growth of senescence-prone neoplastic cells by co-culturing with irradiated fibroblasts and a small molecule Rho kinase inhibitor. These methods help promote the growth of new eye and brain tumor models developed from patient-derived surgical specimens.
Zebra fish modeling of diffuse midline gliomas: We have developed zebra fish models of diffuse midline gliomas (DMG). These pictures show tumors migrating to the brain to accurately model DMGs. Zebra fish models allow us to better image and understand changes in brain tumors over time and shorten the timeframe required to study the efficacy of novel therapeutics