June 27, 2018

This week's JBC issue

This week's JBC issue has Jenna's paper in it.  Check out the full text online.





June 15, 2018

Farewell Jenna

It’s bittersweet that Jenna is leaving our lab to join the Biomed PhD program at Albert Einstein College of Medicine in New York City.  She will be focusing on neuroscience, and she was awarded a Tishman Scholarship as one of their top applicants.  

We are sad to see her go but wish her well on this next step of her career and appreciate her many contributions to the lab over the last 2 years.  Einstein is a great PhD program, and we look forward to hearing about the great research she does there.  Congrats and farewell, Jenna.    

June 12, 2018

Welcome Indi

We are happy to welcome Indiwari (Indi) Gopallawa as our new postdoc starting this week.  Indi did her undergraduate work at North Dakota State University.  She comes to us from Michigan State University, where she earned a PhD in Biochemistry and Molecular Biology working with Dr. Bruce Uhal in the Department of Physiology and also completed some postdoctoral work in the lab of Dr. Richard Neubig in the Department of Pharmacology and Toxicology.  She has a strong background in using biochemical approaches to study cell signaling and cell physiology.  We're very excited to have her join our team and look forward to working with her.  Welcome!

May 10, 2018

Bacterial quinolones and bitter receptors

Thanks to everyone involved in our newly accepted J Biol Chem paper.  It has lots of live cell imaging of calcium indicators and fluorescent protein biosensors to look at signaling in response to T2R activation by a class of bacterial quorum-sensing ligands, quinolones, going from heterologous expression to primary differentiated air-liquid interface cultures.  Jenna is off to grad school at Einstein for neuroscience this summer, so it’s nice to get this one accepted before she leaves the lab.   



March 9, 2018

Postdoc position opening

Funding is now available to have another postdoc join our team.  Bitter and sweet taste receptors are expressed all over the body, yet we know very little about what they do or what ligands they recognize.  Come help us figure out what these and other G-protein coupled receptors do in airway physiology.  Our lab (started in 2015) is a collaborative, enthusiastic, and supportive environment. Training and mentorship will be provided.  Salary/benefits are in line with NIH/NRSA levels. There will be opportunities to work with primary human airway cells in tissue-type air-liquid interface culture models, learn live cell calcium and FRET biosensor imaging and other microscopy techniques.  Topics of interest in our lab include airway physiology and innate immunity, calcium and cAMP signaling, NO signaling, and host-pathogen interactions  

Penn is a fantastic place to work with great colleagues, good postdoc support systems, and good scientific core resources, located in a fun and livable city.  Interact with both world class scientists in the Department of Physiology and world class rhinologists in the Department of Otorhinolaryngology who can help put our science into clinical perspective.

See our official posting here.  A PhD in a biological or related science field is required.  Experience in imaging, cell culture, biochemistry, and/or molecular biology is desirable but not required.

Email Rob (rjl [at] pennmedicine.upenn.edu) a cover letter and CV with the names of 3 references or get in touch if you are interested and have questions.      

December 8, 2017

Penn Med News Blog Featuring Ben's Work

Ben's PLOS One paper on flavones and effects on Pseudomonas was featured on the Penn Medicine News blog.  Thanks to Steve Graff for a great write-up.    

December 5, 2017

Jenna @ ASCB/EMBO 2017

Jenna did a great job representing the lab by presenting a poster yesterday at the American Society for Cell Biology (ASCB)/European Molecular Biology Organization (EMBO) 2017 joint meeting here in Philadelphia at the Pennsylvania Convention Center.  There was lots of great science on hand and she fielded lots of great questions from the crowd.  Congrats, Jenna!    

September 20, 2017

Ben's PLOS One Paper Online

Ben's final first-author paper from the lab went online today at PLOS One.  In it, he showed that plant flavones enhance the efficacy of antibiotics as well as secretions from respiratory epithelial cells against Pseudomonas.  Flavones are also agonists of the bitter taste receptor T2R14, which is expressed in airway cell cilia and activates bactericidal NO responses.  Flavones have two potential therapeutic mechanisms as potential therapeutics for respiratory infections: activation of NO-mediated pathways as well as enhancement of antimicrobial peptide function.  More work is needed to determine if and how to leverage these compounds to stimulate and/or enhance airway cell innate immunity.

Congrats to Ben on a great paper that caps of a very productive time in the lab.  A lot of hard work with into developing/adapting and carrying out off these anti-bacterial assays.  A link to the PDF is here.  

The full citation is

Hariri, B.M., McMahon, D.B., Chen, B., Adappa, N.D., Palmer, J.N., Kennedy, D.W., and Lee, R.J.  "Plant flavones enhance antimicrobial activity of respiratory epithelial cell secretions against Pseudomonas aeruginosa."  PLOS One. 12: e0185203
.          

September 6, 2017

FASEB paper online

We have an in press paper just published online at The FASEB Journal, showing that the protease activated receptor isoform PAR-2 regulates ciliary beat frequency and apical membrane chloride permeability in airway epithelial cells through calcium signaling.

McMahon, D.B., Workman, A.D., Kohanski, M.A., Carey, R.M., Freund, J.R., Hariri, B.M., Chen, B., Dogrhamji, L.J., Adappa, N.D., Palmer, J.N., Kennedy, D.W., and Lee, R.J.  "Protease-activated receptor 2 activates airway apical membrane chloride permeability and increases ciliary beating."  FASEB J.  In Press.

PAR-2 is activated by neutrophil elastase and other immune proteases as well as certain fungal and dust mite proteases.  We show in this paper that PAR-2 activation induces calcium signals that acutely regulate two components of mucociliary clearance: (1) apical membrane chloride permeability necessary for fluid secretion, and (2) ciliary beating necessary for movement of mucus.  

Thanks to Derek, Ben, and Jenna from the lab for their work on the project, as well as Alan Workman, Mike Kohanski, and Ryan Carey for helping with several of the experiments.


Science Signaling Paper Online

We have a paper in the latest issue of Science Signaling:

Lee, R.J., Hariri, B.M., McMahon, D.B., Chen, B., Dogrhamji, L., Adappa, N.D., Palmer, J.N., Kennedy, D.W., Jiang, P., Margolskee, R.F., and Cohen, N.A.  (2017).  "Bacterial D-amino acids suppress sinonasal innate immunity through sweet taste receptors in solitary chemosensory cells."  Science Signaling.  10:eaam7703.

We showed that D-amino acids secreted by Staphylococcus cultures isolated from chronic rhinosinusitis patients produce D-amino acids which activate the sweet taste receptor in airway solitary chemosensory cells.  This may have important implications for host pathogen interactions and may also be important for bacterial cross-talk in the nose.    

Thanks to Ben and Derek from the lab who helped out with the project, which was done in collaboration with Noam Cohen's lab from Penn.  The link to the full text is on our publications page.      

July 31, 2017

CALHM1 ATP Release and Ciliary Beat Frequency

Congrats to Alan Workman (Noam Cohen's lab) on publication of an excellent study of ATP release via the CALHM1 ion channel and control of ciliary beat frequency. The full citation is


Workman AD, Carey, RM, Chen, B, Saunders CJ, Marambaud P, Mitchell CH, Tordoff MG, Lee RJ, and Cohen NA.  (2017).  "CALHM1-Mediated ATP Release and Ciliary Beat Frequency Modulation in Nasal Epithelial Cells."  Scientific Reports.  7:6687.   PMID: 28751666

Alan elegantly shows that ATP release in response to a physiological mechanical stimulus (the level of pressure evoked by a sneeze) is mediated by CALHM1, the same ion channel that mediates ATP release in Type II taste cells (as previously shown by Kevin Foskett's lab here at Penn).  Alan's study is important because studies of ATP release in the airway has primarily focused on pannexins, often with very harsh stimuli (i.e. hypotonic cell swelling).  Alan shows that CALHM1 plays a complementary role to Panx1 (in a more physiological setting) that has so far been completely overlooked in the airway.  It is very nice to see this study finally published and up on Pubmed after a lot of hard work.  The full text is freely available on the Scientific Reports website.

May 22, 2017

Flavone/T2R14 JBC Article in May 19 Issue

We're excited to see our recent flavone/T2R14 J Biol Chem paper in the most recent JBC issue and on the JBC homepage:

May 19, 2017

Derek at the Physiology Department Retreat

Derek gave a short talk on his most recent work on nuclear calcium signaling at the Penn Physiology Dept annual retreat today at Merion Tribute House.  Congrats, Derek, on being selected to speak and great job!  He received lots of great comments and questions on some very exciting preliminary data.      
  

May 18, 2017

Congrats, Andrew!

Congratulations to Andrew on rocking his IGG practice prelim!  It capped off a great rotation.  We will miss him when he leaves the lab at the end of May, and wish him the best as he moves on to his 3rd rotation.   

April 3, 2017

New JBC Paper

A paper we submitted to the Journal of Biological Chemistry was accepted, and the accepted manuscript version is already up online!

Hariri, B.M., McMahon, D.B., Chen, B., Freund, J.R., Mansfield, C.J., Doghramji, L.J., Adappa, N.D., Palmer, J.N., Kennedy, D.W., Reed, D.R., Jiang, P., and Lee, R.J. “Flavones Modulate Respiratory Epithelial Innate Immunity: Anti-Inflammatory Effects and Activation of the T2R14 Receptor." J. Biol. Chem. In Press. PMID: 28373278

We studied a class of biologically active flavonoids, flavones, which have anti-inflammatory effects in primary nasal epithelial cells. Flavones also activate a bitter taste receptor isoform (T2R14) in airway cell cilia, which activates innate immune responses that may be beneficial for treating chronic rhinosinusitis or other infectious respiratory diseases.