Research in Dr. Hernandez’s lab, the Metastasis Biology Section, seeks to interrogate the molecular underpinnings of metastatic colonization in order to interrupt the process prior to its completion. This line of investigation corresponds with a critical need in biomedical research, as metastases are the cause of greater than 90% of cancer related deaths.

For patients undergoing resection, identifying and targeting the mechanisms that support the survival and outgrowth of latent, disseminated tumor cells holds great promise for the prevention of tumor recurrence. The lab has utilized complex cDNA and CRISPR-Cas9 screens to identify genes that conspire to drive the outgrowth of disseminated tumor cells, which ostensibly appear to be involved in epigenetic reprogramming, compensatory metabolism, and extracellular matrix deposition and remodeling. Current efforts are focused on elucidation of mechanisms and signal transduction pathway involvement for the identified genes of interest, to unveil clinically translatable targets.

The lab utilizes multi-photon intravital microscopy to mechanistically interrogate and visualize the dynamics of metastatic outgrowth, including the roles of supporting stromal and immune cells. Moreover, the lab has begun pioneering first-ever human tissue models by repurposing perfusion systems to sustain resected tumor-bearing liver and peritoneum for prolonged ex vivo animation.

We envision these models will enable us to:

1) perform additional screens and validation experiments in human tissue for the first time,

2) personalize investigation of the metastatic cascade by leveraging multi-photon imaging with an individual patient’s tumor cells, which will be dissociated, labelled, and subsequently injected into the perfusate to seed that patient’s metastatic target tissue, and

3) utilize tumor-bearing tissue as a platform for drug discovery and evaluation of novel drug-delivery combinations and platforms, which we think has the potential to transcend multiple disciplines in translational medicine to permit investigations and manipulations not previously possible.