Reynold A. Panettieri, Jr, M.D.
Robert L. Mayock and David A. Cooper Professor of Medicine
Director, Airways Biology Initiative
Adjunct Professor, Wistar Institute
Deputy Director, Center of Excellence in Environmental Toxicology
University of Pennsylvania Medical Center
Pulmonary, Allergy, & Critical Care Division
Translational Research Laboratories (TRL)
125 South 31st Street, TRL Suite 1200
Philadelphia, PA 19104-3413
tel.: (215) 573-9860
fax: (215) 746-1224
Education: M.D., University of Pennsylvania, Philadelphia, PA
Residency: Hospital of the University of Pennsylvania, Philadelphia, PA
Fellowship: Hospital of the University of Pennsylvania, Philadelphia, PA
Dr. Panettieri directs the Airways Biology Initiative at the University of Pennsylvania. His interests are in the cellular and molecular mechanisms that regulate airway smooth muscle cell growth and the immunobiology of airway smooth muscle. Consequences of increases in airway smooth muscle growth promote the development of irreversible airflow obstruction and airway remodeling seen in subjects with chronic severe asthma. Dr. Panettieri's lab also focuses on cytosolic signaling pathways that mediate gene expression and alter myocyte function.
Dr. Panettieri also serves as the Deputy Director of the Center of Excellence in Environmental Toxicology. He directs the human exposure chamber that defines the molecular mechanisms regulating ozone- and particulate matter-induced airway hyperresponsiveness.
In parallel with his basic science interests, Dr. Panettieri currently directs the comprehensive clinical program for the care of patients with asthma and is actively involved in clinical investigations focused on the management of asthma and COPD.
In addition to his research and clinical interests, Dr. Panettieri served as chairperson of the NIH Lung Cellular, Molecular, and Immunobiology Study Section, is a member of the NIH Distinguished Editorial Panel and is a member of the American Society for Clinical Investigation and Association of American Physicians.
Current basic research projects open to fellow participation:
- Immunobiology of airway smooth muscle: A major emphasis of our laboratory focuses on the immunobiology of airway smooth muscle (ASM) cells in asthma and chronic obstructive pulmonary disease (COPD). We have characterized that ASM can orchestrate and perpetuate airway inflammation through the secretion of chemokines/cytokines and expression of cell adhesion molecules. We define the critical signaling pathways by which structural cells modulate inflammatory responses, specifically the interplay of nuclear receptors such as vitamin D and glucocorticoids in inhibiting pro-inflammatory signals in mesenchymal cells.
- Airway smooth muscle growth and airway remodeling: In some but not all patients with asthma, irreversible airflow obstruction occurs that evokes morbidity and mortality. A seminal finding of airway remodeling is increases in ASM mass. Our studies have recently defined that Regulators of G protein coupled Signaling (RGS) modulate ASM contractile responses and promote ASM cell growth. Our studies focus on novel approaches to inhibit ASM growth and maintain the contractile nature of human ASM cells. Specific tools utilize molecular approaches for cell signaling, as well as, novel imaging of cytosolic calcium and confocal bronchoscopy.
- Environmental health studies and airway smooth muscle cell function: Ozone and other environmental toxins can induce airway hyperresponsiveness. The molecular mechanisms regulating ozone-mediated airway inflammation and airway hyperresponsiveness remain unclear. Our studies have defined novel eicosanoids and prostaglandins that mediate ozone-induced inflammation. Using translational biologic approaches in which a human exposure chamber delivers ozone to well-characterized patients with asthma and COPD, the characteristics of airway hyperresponsiveness and the molecular mechanisms regulating these phenotypes are defined. As Deputy Director of the Center of Excellence in Environmental Toxicology (CEET), my laboratory is uniquely suited to investigate environmental health issues surrounding airway hyperresponsiveness, asthma and COPD.
- Novel therapeutic approaches to treat airways diseases: Our laboratory has devoted considerable effort to collaborate with most major pharmaceutical companies to identify novel targets and platforms to test new therapeutic approaches in asthma and COPD. Using precision cut lung slices (PCLS) from humans and mice, the fundamental processes that regulate ASM contraction and growth can be defined, and novel therapeutics to inhibit such processes are characterized.
- Dileepan M, Jude JA, Rao SP, Walseth TF, Panettieri RA, Subramanian S, Kannan MS. MicroRNA-708 regulates CD38 expression through signaling pathways JNK MAP kinase and PTEN/AKT in human airway smooth muscle cells. Respir Res. 2014 Aug 31; 15(1):107. [Epub ahead of print]
- Morgan SJ, Deshpande DA, Tiegs BC, Misior AM, Yan H, Hershfeld AV, Rich TC, Panettieri RA, An SS, Penn RB. Beta-agonist-mediated relaxation of airway smooth muscle is PKA-dependent. J Biol Chem. 2014 Jun 27 [Epub ahead of print]
- Himes BE, Jiang X, Wagner P, Hu R, Wang Q, Klanderman B, Whitaker RM, Duan Q, Lasky-Su J, Nikolos C, Jester W, Johnson M, Panettieri RA Jr, Tantisira KG, Weiss ST, Lu Q. RNA-Seq Transcriptome Profiling Identifies CRISPLD2 as a Glucocorticoid Responsive Gene that Modulates Cytokine Function in Airway Smooth Muscle Cells. PLoS One. 2014 Jun 13;9(6):e99625. eCollection 2014.
- Damera G, Panettieri RA. Irreversible airway obstruction in asthma: What we lose, we lose early. Allergy Asthma Proc. 2014 Mar; 35(2):111-8.
- Balenga NA, Jester W, Jiang M, Panettieri RA Jr, Druey KM. Loss of regulator of G protein signaling 5 promotes airway hyperresponsiveness in the absence of allergic inflammation. J Allergy Clin Immunol. 2014 Mar 22. [Epub ahead of print]
- Fitzgerald R, Desantiago B, Lee DY, Yang G, Kim JY, Brian Foster D, Chan-Li Y, Horton MR, Panettieri RA, Wang R, An SS. H2S relaxes isolated human airway smooth muscle cells via the sarcolemmal KATP channel. Biochem Biophys Res Commun. 2014 Mar 7. [Epub ahead of print]
- Hu R, Pan W, Fedulov AV, Jester W, Jones MR, Weiss ST, Panettieri RA Jr, Tantisira K, Lu Q. MicroRNA-10a controls airway smooth muscle cell proliferation via direct targeting of the PI3 kinase pathway. FASEB J. 2014 Feb 12. [Epub ahead of print]
- Kim WK, Jain D, Sanchez MD, Koziol-White CJ, Matthews K, Ge MQ, Haczku A, Panettieri RA Jr, Frieman MB, Lopez CB. Deficiency of MDA5 Results in Exacerbated Chronic Post-Viral Lung Inflammation. Am J Respir Crit Care Med. 2014 Jan 13.
- Robinett KS, Koziol-White CJ, Akoluk A, An SS, Panettieri Jr RA, Liggett SB. Bitter Taste Receptor Function in Asthmatic and Nonasthmatic Human Airway Smooth Muscle Cells. Am J Respir Cell Mol Biol. 2013 Nov 12.
- Deshpande DA, Yan H, Kong KC, Tiegs BC, Morgan SJ, Pera T, Panettieri RA, Eckhart AD, Penn RB. Exploiting functional domains of GRK2/3 to alter the competitive balance of pro- and anticontractile signaling in airway smooth muscle. FASEB J. 2013 Oct 16. [Epub ahead of print]
- Columbo M, Wong B, Panettieri RA Jr, Rohr AS. The effect of multiple allergen immunotherapy on exhaled nitric oxide in adults with allergic rhinitis. Allergy Asthma Clin Immunol. 2013 Aug 19;9 (1):31.
- Columbo M, Wong B, Panettieri RA Jr, Rohr AS. Asthma in the elderly: The role of exhaled nitric oxide measurements. Respir Med. 2013 May; 107(5):785-7.
- Edelson JD, Makhlina M, Silvester KR, Vengurlekar SS, Chen X, Zhang J, Koziol-White CJ, Cooper PR, Hallam TJ, Hay DW, Panettieri RA Jr. In vitro and in vivo pharmacological profile of PL-3994, a novel cyclic peptide (Hept-cyclo(Cys-His-Phe-D-Ala-Gly-Arg-D-Nle-Asp-Arg-Ile-Ser-Cys)-Tyr-[Arg mimetic]-NH(2)) natriuretic peptide receptor-A agonist that is resistant to neutral endopeptidase and acts as a bronchodilator. Pulm Pulm Pharmacol Ther. 2013 Apr;26(2):229-38. Epub 2012 Nov 12.
- Wang R, Mercaitis OP, Jia L, Panettieri RA, Tang DD. Raf-1, Actin Dynamics and Abl in Human Airway Smooth Muscle Cells. Am J Respir Cell Mol Biol. 2013 Feb;48 (2):172-8. Epub 2012 Oct 18.
- Jude JA, Dileepan M, Panettieri RA Jr, Walseth TF, Kannan MS. Altered CD38/Cyclic ADP-Ribose Signaling Contributes to the Asthmatic Phenotype. J Allergy (Cairo). 2012;2012:289468. Epub 2012 Nov 20.