Congratulations to Zoey on an excellent PGG post-rotation talk to end her first year of grad school. That's a huge accomplishment in normal times let alone a pandemic. Way to go, Zoey!
August 22, 2021
July 23, 2021
July 1, 2021
May 17, 2021
"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.
April 28, 2021
Our new paper on PAR-2 & calcium signaling in nasal gland cells is online at AJP-Lung. Lots of cool techniques were used, from single cell fluid secretion measurements, calcium imaging, polarized epithelial secretion, and a fluorescent GPCR biosensor.
"PAR-2-activated secretion by airway gland serous cells: role for CFTR and inhibition by Pseudomonas aeruginosa" by Derek McMahon, et al. is available here.
August 13, 2020
Li Eon wrote a review for AJP Lung and the accepted version is freely available online. It describes almost everything known about the role of cilia in bacterial, viral, and fungal host pathogen interactions. I hope it becomes a useful resource for people in the field of respiratory infections, particularly as COVID19 draws more attention to the importance of better understanding the respiratory mucosa.
April 2, 2020
March 18, 2020
Our thanks go out to the virologists and physicians working on the front lines to treat patients and develop new treatments for this virus. Out hearts go out to those suffering. Please be kind to one another and let’s all do our part to reduce virus transmission through our communities. We wish you all the best.
March 17, 2020
Macrophages use a signal transduction pathway downstream of T2Rs similar to airway cells, but with a different physiological output (phagocytosis vs cilia beating in the airway). Targeting T2Rs in macrophages might be beneficial in certain types of bacterial infections. Moreover, activation of T2Rs in macrophages by bitter plant products or bitter pharmaceuticals might explain some effects of homeopathic remedies or off target effects of clinical drugs.
January 17, 2020
This award is presented to outstanding young scientists to enable them to present their research at one of the largest biological scientific meetings in the world. The Experimental Biology meeting is a gathering of more than 12,000 scientists from over 65 countries representing the fields of anatomy, physiology, biochemistry, pathology, and pharmacology.