May 17, 2021

New preprints online

Two new preprints from the lab are up on bioRxiv: 
"The bitter end: T2R bitter receptor agonists elevate nuclear calcium and induce apoptosis in non-ciliated airway epithelial cells" by Derek McMahon, et al., available here.


"T2R bitter taste receptors regulate apoptosis and may be associated with survival in head and neck squamous cell carcinoma" by Ryan Carey, et al., available here.

First, postdoc Derek McMahon shows bitter receptors (T2Rs) in non-ciliated airway cells regulate nuclear calcium to induce caspase activation. There are important implications for airway diseases w/ squamous remodeling (eg, CRS, CF, etc.). Similar mechanisms occur in airway cancer cells. We hypothesize that airway tumor-microbiome crosstalk may occur via T2R activation by bacterial homoserine lactones, quinolones, etc. There is a lot to explore further! Derek's paper is also a technical tour de force of live cell imaging of indicator dyes, targeted biosensors to measure sub-cellular calcium, etc. There is lots of tenacious work in there. Nuclear calcium and nuclear GPCRs are very unexplored in airway epithelium.

Taking the observation further, senior Penn NET resident Ryan Carey looked at T2Rs in squamous oral cancer cells & found similar mechanisms (T2Rs, nuclear calcium, apoptosis). Ryan's data suggests T2R agonists, particularly in high doses in accessible anatomic sites (like the oral cavity), might be therapeutic for HNSCC. Ryan analyzed The Cancer Genome Atlas and found increased T2R expression is beneficial for HNSCC survival. Perhaps T2Rs are a new type of HNSCC biomarker (requires lots of followup). This was amazing work for a resident research project!

There is a lot of new stuff for them/the lab to follow up on and new leads to pursue, but I'm very proud of their hard work, taking us further in both old & new directions for T2Rs in human epithelial biology w/ translational potential. While others have shown or suggested roles for T2Rs in apoptosis and cancers, Derek showed unique mechanisms to how/why T2Rs signal to apoptosis. Ryan showed an important relevance to a human cancer where activating T2Rs (e.g., via a mouth rinse) is very doable, not just a "what if" scenario.