Laboratory of Rare Lung Diseases
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
M.D., University of Pennsylvania, Philadelphia, PA
Hospital of the University of Pennsylvania, Philadelphia, PA
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.
- Panettieri RA Jr. Bronchial Thermoplasty: Targeting Structural Cells in Severe Persistent Asthma. Ann Am Thorac Soc. 2015 Nov;12 (11):1593-4.
- Carr R, Koziol-White C, Zhang J, Lam H, An SS, Tall GG, Panettieri RA, Benovic JL. Interdicting Gq Activation in Airway Disease by Receptor-Dependent and Receptor-Independent Mechanisms. Mol Pharmacol. 2015 Oct 13. [Epub ahead of print]
- Liao G, Panettieri RA, Tang DD. MicroRNA-203 negatively regulates c-Abl, ERK1/2 phosphorylation, and proliferation in smooth muscle cells. Physiol Rep. 2015 Sep;3(9). pii: e12541.
- Sun Y, Jain D, Koziol-White CJ, Genoyer E, Gilbert M, Tapia K, Panettieri RA Jr, Hodinka RL, López CB. Immunostimulatory Defective Viral Genomes from Respiratory Syncytial Virus Promote a Strong Innate Antiviral Response during Infection in Mice and Humans. PLoS Pathog. 2015 Sep 3; 11(9):e1005122. eCollection 2015 Sep.
- Kohli P, Pinto-Plata V, Divo M, Malhotra A, Harris RS, Lazaar A, Flynn A, Tal-Singer R, Panettieri RA Jr, Celli B. Functional Capacity, Health Status, and Inflammatory Biomarker Profile in a Cohort of Patients With Chronic Obstructive Pulmonary Disease. J Cardiopulm Rehabil Prev. 2015 Sep-Oct; 35(5):348-55.
- Panettieri RA Jr. Bronchodilators, receptors and cross-talk: together is better? Postgrad Med. 2015 Aug 21:1-10. [Epub ahead of print]
- Himes BE, Koziol-White C, Johnson M, Nikolos C, Jester W, Klanderman B, Litonjua AA, Tantisira KG, Truskowski K, MacDonald K, Panettieri RA Jr, Weiss ST. Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthma. PLoS One. 2015 Jul 24; 10(7):e0134057. eCollection 2015.
- Jemielita T, Gerton GL, Neidell M, Chillrud S, Yan B, Stute M, Howarth M, Saberi P, Fausti N, Penning TM, Roy J, Propert KJ, Panettieri RA Jr. Unconventional Gas and Oil Drilling Is Associated with Increased Hospital Utilization Rates. PLoS One. 2015 Jul 15;10(7):e0131093. eCollection 2015.
- McGeachie MJ, Wu AC, Tse SM, Clemmer GL, Sordillo J, Himes BE, Lasky-Su J, Chase RP, Martinez FD, Weeke P, Shaffer CM, Xu H, Denny JC, Roden DM, Panettieri RA Jr, Raby BA, Weiss ST, Tantisira KG. CTNNA3 and SEMA3D: Promising loci for asthma exacerbation identified through multiple genome-wide association studies. J Allergy Clin Immunol. 2015 Jun 12. pii: S0091-6749(15)00646-6. [Epub ahead of print]
- Gupta MK, Asosingh K, Aronica M, Comhair S, Cao G, Erzurum S, Panettieri RA Jr, Naga Prasad SV. Defective Resensitization in Human Airway Smooth Muscle Cells Evokes β-Adrenergic Receptor Dysfunction in Severe Asthma. PLoS One. 2015 May 29;10(5):e0125803. eCollection 2015.
- Balenga NA, Klichinsky M, Xie Z, Chan EC, Zhao M, Jude J, Laviolette M, Panettieri RA Jr, Druey KM. A fungal protease allergen provokes airway hyper-responsiveness in asthma. Nat Commun. 2015 Apr 13;6:6763.
- Guedes AG, Deshpande DA, Dileepan M, Walseth TF, Panettieri RA Jr, Subramanian S, Kannan MS. CD38 and airway hyper-responsiveness: studies on human airway smooth muscle cells and mouse models. Can J Physiol Pharmacol. 2015 Feb;93 (2):145-53. [Epub ahead of print]
- Sharma A, Menche J, Huang C, Ort T, Zhou X, Kitsak M, Sahni N, Thibault D, Voung L, Guo F, Gulbahce N, Baribaud F, Tocker J, Dobrin R, Barnathan E, Liu H, Panettieri RA Jr, Tantisira KG, Qiu W, Raby BA, Silverman EK, Vidal M, Weiss ST, Barabási AL. A disease module in the interactome explains disease heterogeneity, drug response and captures novel pathways and genes. Hum Mol Genet. 2015 Jan 12. [Epub ahead of print]
- Carr R 3rd, Du Y, Quoyer J, Panettieri RA Jr, Janz JM, Bouvier M, Kobilka BK, Benovic JL. Development and Characterization of Pepducins as Gs-biased Allosteric Agonists. J Biol Chem. 2014 Nov 13. [Epub ahead of print]
- Marozkina NV, Wang XQ, Stsiapura V, Fitzpatrick A, Carraro S, Hawkins GA, Bleecker E, Meyers D, Jarjour N, Fain SB, Wenzel S, Busse W, Castro M, Panettieri RA Jr, Moore W, Lewis SJ, Palmer LA, Altes T, de Lange EE, Erzurum S, Teague WG, Gaston B. Phenotype of asthmatics with increased airway S-nitrosoglutathione reductase activity. Eur Respir J. 2014 Oct 30. [Epub ahead of print]