miRNA as therapuetics: We are exploring how ‘cocktails’ of miRNA can be given to modify global gene expression programs in glioblastoma, focusing on the EGFR pathway, a common amplification in adult patients with GBM. In the recurrent state, glioblastomas overexpress the EGFR pathway (despite a lack of amplification) and we will test whether the resistant state can be abrogated using miRNA targeting, serving as a proof of concept for a novel class of therapeutics in this disease.
Radiomics and machine learning: Using novel methods of data analysis, we are developing new biomarkers and tools to help with understanding how brain tumors and metastatic disease to the brain evolves over time, and how to make better, more informed clinical decisions based on this information.
circRNA: An enigmatic and challenging aspect of RNA biology is what to do with the unmapped reads that come from standard RNA sequencing. Within this set of unmapped reads, a species of non-linear (circular) RNA molecules was found, resistant to degradation by common RNAse enzymes, and with a poorly understood role in cancer biology. We are working on ways to better identify these species of non-coding RNA and understand their function.
Mathematical models of tumor evolution: The evolution of therapeutic resistance is the major issue in the treatment of central nervous system malignancies. By writing computer programs and equation systems that rely on basic assumptions of how tumors grow and evolve, we can better understand real-world tumor genetic data to recapitulate how evolution has occurred in a cancer. By understanding this, we hope to generate an understanding of how tumor evolution can be directed by therapies to prolong survival.
Neurological manifestations of PTEN hamartoma tumor syndrome: PTEN hamartoma tumor syndrome is an inherited predisposition to cancer, but with significant potential effects on neurodevelopment as well. Through collaborations with the Eng lab at the Lerner Research Institue, Cleveland Clinic, we are examining the neurological phenotypes in this condition, and using this to better define clinical trial endpoints and clinical care guidelines.
Genotype-phenotype mapping in tuberous sclerosis complex: In collaboration with the Epilepsy Center at the Cleveland Clinic, we have been working on using high-dimensional semisupervised and unsupervised clustering methods on large datasets describin gthe phenotypes of patietns with tuberous sclerosis complex (TSC) to better define the genotype-phenotype map, with the goal of fostering early intervention in the most severe cases.
Climate and neurological health: Our group has produced the first large-scale review of the neurological effects of climate change. As this is an issue of pressing global concern, we are committed to identifying better ways of not only measuring the health effects of climate change at a population level, but better understanding its effect through a mechanistic level.