Integration of Metabolic and Signaling Pathways

Our lab explores the integration of metabolic and signaling pathways that regulate cancer development and progression. We are interested in elucidating the mechanisms by which cellular metabolism regulates the normal development of the nervous system and how metabolic alterations are linked to nervous system disorders including brain tumors.

We examine cellular energy sensors and metabolic regulators in brain development tumorigenesis including the role of the energy sensor AMPK and the anabolic kinase mTOR. AMP-activated protein kinase (AMPK) is a molecular hub of metabolic control in all eukaryotic cells and functions at the crossroads of several signaling pathways.

We are investigating the context-dependent functions of the AMPK-mTOR signaling axis during normal development and tumorigenesis, why some cancer cells are sensitive while others are resistant to mitochondrial and glycolytic poisons and if this axis provides cellular protection through drug resistance.

Unintended Gene Deletions

Another aim of our laboratory is to investigate the consequence of unintended gene deletions in cancer. Out of the thousands of genes deleted or amplified in human cancer, most are called passengers that occur unintentionally along with driver gene alterations.

We are examining if these unintended alterations that survived negative selection during tumor evolution are critical for tumor biology and can be targeted in a cancer subtype-specific manner.

Links for External, Intrinsic Risk Factors

A third area that we have begun to explore is to understand the molecular links between external and intrinsic risk factors in the etiology of human cancer. Despite strong evidence of substantial contribution of external risk factors to cancer development, the molecular link between specific external factors and specific genetic alterations is a relatively new and highly significant area of investigation.

Our goal is to understand the relationship between external and cell-intrinsic factors that influence cancer incidence, penetrance, development and progression.

Discovering Novel Targets in Pediatric Brain Tumors

Pediatric Diffuse Intrinsic Pontine Glioma (DIPG) is a rare but incurable childhood cancer. Towards a better understanding of DIPG, we have developed orthotopic xenograft mouse models of DIPG using a panel of DIPG cell lines. Genes and metabolites ultimately control the behavior and fate of living cells, and tumor metabolic program controls every aspect of tumor biology including growth, survival and metastasis. Unravelling gene‐metabolite interactions may lead to discovery of novel pathways that can be targeted with new or repurposed drugs. We generated the first comprehensive gene‐metabolite interactome to identify targetable pathways in DIPGs.