Congratulations to Zoey, who is now Dr. Zoey! She successfully defended her PhD thesis on Nov 22nd! She did a great job, and we're all very proud!
Lee Lab
Laboratory for GPCR Signaling in Epithelial Physiology
Department of Otorhinolaryngology–Head and Neck Surgery
Division of Rhinology
University of Pennsylvania Perelman School of Medicine
Philadelphia, PA USA
November 22, 2024
November 13, 2024
Ines and Joel's paper online at IFAR
Inès and Joel have a great paper available online (open access, so freely available) today at International Forum of Allergy and Rhinology! They studied bitter beta-acids from hops (yes, the same hops used for beer). We hypothesized that these compounds (lupulone and colupulone) might be beneficial by both activating bitter taste receptors (taste family 2 receptors, or T2Rs) in the nose to stimulate beneficial innate defense responses. These compounds, often referred to as "antibiotics" in older medical literature, also have antibacterial properties. Lupulone and colupulone were used for tuberculosis in people after World War II, but they were abandoned in favor of conventional antibiotics as antibiotics improved for TB, and because the beta-acids had some gastrointestinal side effects. Inès and Joel carried out a very rigorous and interesting study using a variety of techniques, including fluorescent biosensors, live cell imaging of indicator dyes, biochemistry, microbiology, etc. in both primary nasal cells and nasal cancer cells.
They found that while lupulone and colupulone are bactericidal against methicillin-resistant Staph. aureus (MRSA), these compounds also have detrimental impacts on nasal epithelial mitochondria and cilia function. This is possibly because they activate a new T2R isoform, T2R1, which does not have strict cilia localization like many of the other T2R isoforms we studied in nasal epithelial cells. Lupulone and Colupulone also stimulated robust remodeling in primary cells differentiated at air-liquid interface. Epithelial remodeling is the process by which the cells that make up the epithelium change in type and/or composition. Remodeling occurs in a variety of airway diseases like chronic rhinosinusitis or cystic fibrosis. While lupulone and colupulone specifically don't look promising for development as new topical T2R-targeting or antibacterial therapies, this work sheds new light onto how T2Rs signal in the nose, including new mechanisms of how they might impinge on epithelial remodeling. This study demonstrates that we don't yet know everything about what T2Rs do in the nose. Derivatives of these compounds might also be useful if analogues can be made to not activate T2R1 but still have anti-MRSA properties.
July 26, 2024
Zoey's GLUT1 paper now online
Zoey's second paper is now online at Cell Death Discovery! She studied how a GLUT1 inhibitor causes apoptosis in head and neck cancer cells. At lower concentrations, this GLUT1 inhibitor also sensitizes cancer cells to bitter taste receptor agonists to enhance their apoptotic effects. Great work Zoey! Another important contributor to this work (and second author!) was our Penn IDEAL SUIP student Sahil Muthuswami. You can read the open access (freely available) paper online here.
November 22, 2023
Zoey's paper online
Zoey's paper on lidocaine activation of T2R14 in head and neck cancer is now online at Cell Reports and was spotted on AppleNews and in Newsweek. Congrats, Zoey!
November 2, 2023
August 1, 2023
Welcome Jordan and Alex
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!
June 30, 2023
Zoey wins Blavatnik Fellowship
We're very proud that Penn Pharmacology grad student Zoey Miller from our lab was just awarded a prestigious Blavatnik Family Fellowship, generously sponsored by The Blavatnik Family Foundation, which will support her to work on T2R bitter receptors in HNSCCs over the coming academic year. Congratulations Zoey! This is one of the most prestigious awards given to Penn Biomedical Graduate Studies students. We are very grateful for generosity of Blavatnik Family Foundation supporting these awards, and very grateful they also saw what we already knew: that Zoey was incredibly deserving of the award. Great job!
May 17, 2023
New Review
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
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
November 1, 2021
New paper online at Molecular Oncology
September 27, 2021
New paper online at Nutrients
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!