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.

January 18, 2017

Welcome, Andrew and Supriya!

Welcome to Andrew, our spring rotation student from the Penn BGS Immunology Graduate Group.  We also welcome Supriya, a student in the Masters in Biotechnology Program in the School of Engineering.  We're excited to have them working in the lab.  

January 13, 2017

We've moved!

Our lab new address is 1222/1223 Biomedical Research Building (BRB) and Rob's office has moved to 1209 BRB.  We're excited and working hard to get the new space up and running.  

Check out the view of downtown Philly from our floor:

  

October 6, 2016

Welcome, Jenna!

Welcome to Jenna, our new research specialist!  We look forward to having her as part of the team.

September 15, 2016

Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary Function

Aflatoxins are produced by certain species of Aspergillus fungi, and are important because they are among the most potent liver carcinogens known to man.  They can be found as contaminants in improperly stored grains, nuts, and other staple foods, and ingestion of aflatoxin-contaminated foods is a major public health concern in certain parts of the world.  However, inhalation of aflatoxins during occupational exposure to dust from contaminated grains has also been linked to lung cancer.

Our recent study, published in Nature's Scientific Reports, shows that aflatoxins can also have more acute effects on airway ciliary motile and sensory function by activation of protein kinase C, which slows ciliary beating and reduces taste-receptor-dependent nitric oxide production.  The aflatoxin-producing Aspergillus flavus is the second leading cause of invasive fungal sinusitis worldwide, and aflatoxin secretion may be a way for these fungi to impair innate immunity during infection.

July 28, 2016

In vitro Effects of Anthocyanidins on Sinonasal NO Production and Bacterial Physiology

Ben's first paper with the lab (Hariri, B.M., et al.  2016.  "In vitro Effects of Anthocyanidins on Sinonasal Epithelial Nitric Oxide Production and Bacterial Physiology."  American Journal of Rhinology and Allergy.  30:261-268.) is up on PubMed and on the AJRA website.  Congrats, Ben!  

We found that a biologically active class of flavonoids, anthocyanidins, stimulate taste-receptor independent NO production from airway epithelial cells.  However, these compounds increase bacterial swimming motility, which might be bad from a therapeutic standpoint.  These results highlight the benefits of testing potential therapeutic compounds in in vitro assays, including in vitro bacterial assays, to better predict their effects in vivo.  

There are more papers on the horizon from Ben's work....       

May 18, 2016

Welcome

Welcome to Maddie, our first summer undergrad student in the lab!    

April 28, 2016

Food for Thought

"If you torture the data long enough, it will confess to anything." 
--British economist Ronald Coase (1910-2013)

Apparently there is some disagreement on the exact wording of this quote, but I like the message of this version.