Robert Lee

Associate Professor

View Lab Website Arrow Icon

M8C Stellar-Chance

422 Curie Boulevard

Philadelphia, PA 19104

Research Description

We study the physiology of epithelial cells lining the upper airway (nose and sinuses) and lung to understand how they sense and respond to pathogens. We combine biochemistry and molecular biology with real-time optical measurements of airway cell signaling and associated physiological responses, including ciliary beating, calcium signaling, fluid secretion, ion transport, nitric oxide production, and antimicrobial peptide secretion. We mainly utilize human primary cells, including nasal cells isolated from residual surgical tissue and then used acutely or cultured and differentiated at air-liquid interface to mimic the in vivo airway epithelium.  Our goal is to better understand the cellular and molecular mechanisms underlying airway diseases to identify novel molecular targets for new therapies.  We have a close partnership with rhinologist surgeons at the Hospital of the University of Pennsylvania that allows ideas generated in our lab to be directly tested or evaluated in a clinical setting.

Our major disease focus is chronic rhinosinusitis (CRS), a disease of chronic upper respiratory infection and inflammation affecting 8-10% of the US population with direct healthcare costs of over $6 billion annually in the US.  Upper respiratory infections account for 1 out of every 5 antibiotic prescriptions in adults in the US, making their treatment a major contributor to the emergence of antibiotic-resistant organisms.  A continuing goal of our research is to identify new and better therapies to treat CRS and other airway diseases without the use of antibiotics, particularly through the stimulation of endogenous innate immune pathways.  A major focus of our work is on bitter taste receptors (known as T2Rs), which detect bitter taste on the tongue but are also expressed in the airway epithelium and in immune cells like macrophages.   In the airway, these T2Rs stimulate calcium and nitric oxide signaling that activates antibacterial defenses.  Genetic polymorphisms in some T2R genes are linked to CRS susceptibility.  Our goal is to better define the roles of T2Rs in human physiology and pathophysiology.      

We also study cystic fibrosis (CF), the most common lethal recessive genetic diseases in the US.  CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel.  We are interested in how and why the secretion of the fluid lining the lung, called airway surface liquid, is altered in CF airways.  We use imaging of primary nasal cells to study real time fluid secretion and fluid composition from both non-CF and CF cells.  We are also studying how alterations of intracellular signaling lead to increased inflammatory responses in CF airway cells.     

Degrees & Education

BS (Molecular Biology), University of Pittsburgh, PA, 2003

PhD (Cell and Molecular Biology), University of Pennsylvania Perelman School of Medicine, PA, 2008

Honors & Awards

Ann Weinberg Memorial Postdoctoral Research Fellowship, Cystic Fibrosis Foundation (2009-2011)

National Science Foundation Graduate Research Fellowship (2004 - 2007)

Other Perelman School of Medicine Affiliations

Penn Division of Rhinology

University of Pennsylvania Institute for Translational Medicine and Therapeutics

Professional Affiliations

American Society for Biochemistry and Molecular Biology

American Physiological Society

Recent Publications
November 16, 2023
Lidocaine induces apoptosis in head and neck squamous cell carcinoma through activation of bitter taste receptor T2R14
Robert J. Lee, Ph.D
Miller ZA, Mueller A, Kim T, Jolivert JF, Ma RZ, Muthuswami S, Park A, McMahon DB, Nead KT, Carey RM, Lee RJ. - DOI: 10.1016/j.celrep.2023.113437
Article Arrow Icon
September 1, 2022
Bitter taste receptor-stimulated nitric oxide innate immune responses are reduced by loss of CFTR function in nasal epithelial cells and macrophages
Robert J. Lee, Ph.D
Carey RM, Palmer JN, Adappa ND, Lee RJ. [preprint]. 2022 September.
Article Arrow Icon
May 27, 2022
Impact of sweet, umami, and bitter taste receptor (TAS1R and TAS2R) genomic and expression alterations in solid tumors on survival.
Robert J. Lee, Ph.D
Carey RM, Kim T, Cohen NA, Lee RJ, Nead KT. Sci Rep. 2022 May 27;12(1):8937. doi: 10.1038/s41598-022-12788-z. PMID: 35624283; PMCID: PMC9142493.
Article Arrow Icon
April 16, 2022
T2R bitter taste receptors regulate apoptosis and may be associated with survival in head and neck squamous cell carcinoma
Robert J. Lee, Ph.D
Carey RM, McMahon DB, Miller ZA, Kim T, Rajasekaran K, Gopallawa I, Newman JG, Basu D, Nead KT, White EA, Lee RJ. DOI: 10.1002/1878-0261.13131
Article Arrow Icon
April 6, 2022
Cilia Stimulatory and Antibacterial Activities of T2R Bitter Taste Receptor Agonist Diphenhydramine: Insights into Repurposing Bitter Drugs for Nasal Infections
Robert J. Lee, Ph.D
Kuek LE, McMahon DB, Ma RZ, Miller ZA, Jolivert JF, Adappa ND, Palmer JN, Lee RJ. DOI: 10.3390/ph15040452
Article Arrow Icon
November 8, 2021
The bitter end: T2R bitter receptor agonists elevate nuclear calcium and induce apoptosis in non-ciliated airway epithelial cells
Robert J. Lee, Ph.D
McMahon DB, Kuek LE, Johnson ME, Johnson PO, Horn RLJ, Carey RM, Adappa ND, Palmer JN, Lee RJ - doi: 10.1016/j.ceca.2021.102499
Article Arrow Icon
October 30, 2021
T2R bitter taste receptors regulate apoptosis and may be associated with survival in head and neck squamous cell carcinoma
Robert J. Lee, Ph.D
Carey RM, McMahon DB, Miller ZA, Kim T, Rajasekaran K, Gopallawa I, Newman JG, Basu D, Nead KT, White EA, Lee RJ - doi: 10.1002/1878-0261.13131
Article Arrow Icon
October 19, 2021
Small-molecule Akt-activation in airway cells induces NO production and reduces IL-8 transcription through Nrf-2
Robert J. Lee, Ph.D
Gopallawa I, Kuek LE, Adappa ND, Palmer JN, Lee RJ - doi: 10.1186/s12931-021-01865-y
Article Arrow Icon
September 22, 2020
Targeting the phosphoinositide-3-kinase/protein kinase B pathway in airway innate immunity
Robert J. Lee, Ph.D
Gopallawa, I. and Lee, R.J - DOI: 10.4331/wjbc.v11.i2.30
Article Arrow Icon
March 14, 2021
Bitter taste receptors stimulate phagocytosis in human macrophages through calcium, nitric oxide, and cyclic-GMP signaling
Robert J. Lee, Ph.D
Gopallawa, I., Freund, J.R., and Lee, R.J. - DOI: 10.1007/s00018-020-03494-y
Article Arrow Icon
March 4, 2021
PAR-2-activated secretion by airway gland serous cells: role for CFTR and inhibition by Pseudomonas aeruginosa
Robert J. Lee, Ph.D
McMahon, D.B., Carey, R.M., Kohanski, M.A., Adappa, N.D., Palmer, J.N., and Lee, R.J. - DOI: 10.1152/ajplung.00411.2020
Article Arrow Icon
ALL Publications Arrow Icon