We welcome Jordan Williams (Penn PGG grad student) and Alex Simon (Penn Postdoc) who are starting in the lab this week. We're excited that you are both here!
August 1, 2023
June 30, 2023
Zoey wins Blavatnik Fellowship
May 17, 2023
New Review
Postdoc Inès wrote a very nice and very comprehensive review on T2Rs in host-pathogen interactions, just published in Microorganisms: https://www.mdpi.com/2076-2607/11/5/1295
April 24, 2023
AChemS 2023
Zoey and Rob represented the lab at the 2023 AChemS meeting in Florida. It was great to catch up with colleagues and learn about lots of new exciting taste research! Zoey's poster was very well attended (there was a line) and Rob got some great questions after his talk. All in all, it was a successful trip!
December 17, 2021
Postdoc Openings
We have space and funding for at least two new postdocs in the lab. Funding is available for a postdoctoral fellow to study epithelial signaling in innate immunity, specifically how G-protein coupled receptors activate antimicrobial responses in nasal and lung cells. Another postdoctoral position is available to study GPCR taste receptor signaling in immune cells like macrophages and dendritic cells.
Our lab uses a combination of live-cell and confocal imaging, biochemistry, and molecular biology approaches using primary human cells isolated from nasal surgical samples and cultured at air-liquid interface. A main focus of our lab is bitter taste receptors, which are expressed in many tissues beyond just the tongue, where they serve largely unknown roles. In the airway, bitter taste receptors detect bacterial products and activate calcium-driven innate immune responses. In macrophages, bitter taste receptors receptors regulate phagocytosis through calcium and nitric oxide signaling.
Our lab is located within the Division of Rhinology in the Department or Otorhinolaryngology. More about our lab’s research, equipment and resources, and recent publications by students and postdocs, can be found at www.robleelab.com
The postdoc will work closely with the PI and other lab members and receive training in live-cell imaging and other techniques as needed, potentially including measurements of calcium, nitric oxide, pH, ciliary beat frequency, fluid secretion, phagocytosis, and/or imaging of fluorescent protein biosensors. The postdoc will also be expected to independently or collaboratively develop or learn new techniques as required by the project. Opportunities for professional development (grant writing, review writing, collaborations, conferences, etc.) will be encouraged and supported. Salary and benefit information (based on NIH NRSA stipend levels) and information about postdoctoral policies at Penn are outlined on the Biomedical Postdoctoral Programs website.
A PhD in a biological science (cell biology, molecular biology, immunology, physiology, etc.), with demonstration of successful completion of thesis project. Experience in cell culture, biochemistry, and/or imaging is highly desirable, but not required. Communication skills (reading, writing, speaking), enthusiasm, and good interpersonal skills are essential. We encourage individuals from underrepresented racial and ethnic groups, and individuals from socially, culturally, economically, or educationally disadvantaged backgrounds to apply.
Please email a cover letter and CV, including publications and the names of three references, to Rob (rjl [at] pennmedicine [dot] upenn [dot] edu).
Our lab is located within the Division of Rhinology in the Department or Otorhinolaryngology. More about our lab’s research, equipment and resources, and recent publications by students and postdocs, can be found at www.robleelab.com
The postdoc will work closely with the PI and other lab members and receive training in live-cell imaging and other techniques as needed, potentially including measurements of calcium, nitric oxide, pH, ciliary beat frequency, fluid secretion, phagocytosis, and/or imaging of fluorescent protein biosensors. The postdoc will also be expected to independently or collaboratively develop or learn new techniques as required by the project. Opportunities for professional development (grant writing, review writing, collaborations, conferences, etc.) will be encouraged and supported. Salary and benefit information (based on NIH NRSA stipend levels) and information about postdoctoral policies at Penn are outlined on the Biomedical Postdoctoral Programs website.
A PhD in a biological science (cell biology, molecular biology, immunology, physiology, etc.), with demonstration of successful completion of thesis project. Experience in cell culture, biochemistry, and/or imaging is highly desirable, but not required. Communication skills (reading, writing, speaking), enthusiasm, and good interpersonal skills are essential. We encourage individuals from underrepresented racial and ethnic groups, and individuals from socially, culturally, economically, or educationally disadvantaged backgrounds to apply.
Please email a cover letter and CV, including publications and the names of three references, to Rob (rjl [at] pennmedicine [dot] upenn [dot] edu).
November 8, 2021
New paper online at Cell Calcium
Derek's paper is now online at Cell Calcium (McMahon, et al., https://doi.org/10.1016/j.ceca.2021.102499).
Years of tenacious work revealed important changes in T2R signaling that occur with airway epithelial squamous de-differentiation. This paper is a tour-de-force of live cell imaging of indicator dyes and genetically encoded targeted probes for subcellular calcium imaging. We're very proud of this work, and it may reveal novel pathogenic mechanisms in disease where airway de-differentiation occurs, such as COPD, asthma, or chronic rhinosinusitis.
Rather than activating calcium in cilia to increase NO production and ciliary beating, T2R activation in non-ciliated airway cells induces strong nuclear calcium responses that propagate to the mitochondria. This results in mitochondrial depolarization, caspase activation, and apoptotic cell death. This may be a last-resort defense against bacterial infection. However, it may also increase susceptibility of de-differentiated or remodeled epithelia to damage by bacterial metabolites. Moreover, the T2R-activated apoptosis pathway occurs in airway cancer cells. T2Rs may thus contribute to microbiome-tumor cell crosstalk in airway cancers. Targeting T2Rs may be useful for activating cancer cell apoptosis while sparing surrounding tissue.
Congrats, Derek!
November 1, 2021
New paper online at Molecular Oncology
Ryan's paper is now online at Molecular Oncology (Carey, et al., https://doi.org/10.1002/1878-0261.13131).
This paper goes from sub-cellular calcium imaging to patient outcomes, showing important roles for T2Rs in head and neck cancer. We're very proud of this awesome paper! Congrats Ryan!
September 27, 2021
New paper online at Nutrients
Ryan Carey has a paper with out today in Nutrients: "Neuropeptide Y Reduces Nasal Epithelial T2R Bitter Taste Receptor–Stimulated Nitric Oxide Production" Great work, Ryan! https://doi.org/10.3390/nu13103392
In a nutshell, NPY may be elevated in the airways in sinus diseases or in asthma. NPY is also one of few negative regulators of airway cilia beating (via NPY2R receptors and PKC). This paper shows the same NPY2R/PKC pathway reduces cilia bitter receptor NO, linking NPY with impaired innate defense.
Airway neuropeptides (NPY, VIP, SubP, etc.) have diverse effects via GPCRs on airway epithelial & immune cells. While likely important for airway physiology & pathophysiology, we still don't know enough about how they influence these cells. Because T2R bitter receptor signaling to eNOS and production of NO controls other responses (like macrophage phagocytosis), NPY (or related PP or PYY) may also reduce T2R-mediated responses in other tissues (but likely depends on NPYRs expressed there). How do other neuropeptides regulate T2R responses in the airway? Stay tuned.
In a nutshell, NPY may be elevated in the airways in sinus diseases or in asthma. NPY is also one of few negative regulators of airway cilia beating (via NPY2R receptors and PKC). This paper shows the same NPY2R/PKC pathway reduces cilia bitter receptor NO, linking NPY with impaired innate defense.
Airway neuropeptides (NPY, VIP, SubP, etc.) have diverse effects via GPCRs on airway epithelial & immune cells. While likely important for airway physiology & pathophysiology, we still don't know enough about how they influence these cells. Because T2R bitter receptor signaling to eNOS and production of NO controls other responses (like macrophage phagocytosis), NPY (or related PP or PYY) may also reduce T2R-mediated responses in other tissues (but likely depends on NPYRs expressed there). How do other neuropeptides regulate T2R responses in the airway? Stay tuned.
September 1, 2021
Congrats Zoey!
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
Welcome Jenn!
Year-out Penn med student Jenn Jolivert joined the lab to help work on bitter receptors in head and neck cancer over the year. Welcome Jenn! We hope you have a great research experience!
July 23, 2021
Farewell, Li Eon!
Today was Li Eon's last day. He is leaving for a position as the scientific director of the Citrin Foundation in Singapore. We are sad to see him go, but we are excited about this new opportunity and new direction in his career path. Li Eon joined us as a postdoc in 2018 and became a master of primary airway epithelial cell culture. He was an expert on all things cilia, and wrote an excellent review last year in AJP Lung. We expect him to do great things in his career and look forward to hearing about all of his future accomplishments. We wish the best to Li Eon as he takes this next exciting step in his life. We will work hard to continue all of the great projects he started during his time in the lab.
July 1, 2021
Welcome Zoey!
Pharmacology grad student Zoey Miller joined the lab to work on bitter taste receptor signaling in head and neck cancer. Welcome Zoey! We hope you have a great time in the lab and we look forward to all the great things you will do.
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.
and
"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.
"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.
and
"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
New paper at AJP Lung
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
New cilia review online
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.
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