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.
- 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.
- Bair AM, Turman MV, Vaine CA, Panettieri RA Jr, Soberman RJ. The nuclear membrane leukotriene synthetic complex is a signal integrator and transducer. Mol Biol Cell. 2012 Nov;23(22):4456-64. Epub 2012 Sep 26.
- Gunst SJ, Panettieri RA Jr. Last Word on Point: Alterations in airway smooth muscle phenotype do cause airway hyperresponsiveness in asthma. J Appl Physiol. 2012 Sep;113(5):847. No abstract available. PMID: 22942224
- Black JL, Panettieri RA Jr, Banerjee A, Berger P. Airway smooth muscle in asthma: just a target for bronchodilation? Clin Chest Med. 2012 Sep;33(3):543-58. Epub 2012 Jul 11. PMID: 22929101
- Himes BE, Jiang X, Hu R, Wu AC, Lasky-Su JA, Klanderman BJ, Ziniti J, Senter-Sylvia J, Lima JJ, Irvin CG, Peters SP, Meyers DA, Bleecker ER, Kubo M, Tamari M, Nakamura Y, Szefler SJ, Lemanske RF Jr, Zeiger RS, Strunk RC, Martinez FD, Hanrahan JP, Koppelman GH, Postma DS, Nieuwenhuis MA, Vonk JM, Panettieri RA Jr, Markezich A, Israel E, Carey VJ, Tantisira KG, Litonjua AA, Lu Q, Weiss ST. Genome-Wide Association Analysis in Asthma Subjects Identifies SPATS2L as a Novel Bronchodilator Response Gene. PLoS Genet. 2012 Jul;8(7):e1002824. Epub 2012 Jul 5.
- Jude JA, Dileepan M, Subramanian S, Solway J, Panettieri RA Jr, Walseth TF, Kannan MS. MIR-140-3P regulation of TNF-induced CD38 expression in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2012 Jul 6. [Epub ahead of print]
- Koziol-White CJ, Goncharova EA, Cao G, Johnson M, Krymskaya VP, Panettieri RA Jr. DHEA-S inhibits human neutrophil and human airway smooth muscle migration. Biochim Biophys Acta. 2012 Jul 3. [Epub ahead of print]
- Xie Y, Jiang H, Nguyen H, Jia S, Berro A, Panettieri RA Jr, Wolff DW, Abel PW, Casale TB, Tu Y. Regulator of G protein signaling 2 is a key modulator of airway hyperresponsiveness. J Allergy Clin Immunol. 2012 Jun 14. [Epub ahead of print]
- An SS, Wang WC, Koziol-White CJ, Ahn K, Lee DY, Kurten RC, Panettieri RA Jr, Liggett SB. TAS2R Activation Promotes Airway Smooth Muscle Relaxation Despite B2-Adrenergic Receptor Tachyphylaxis. Am J Physiol Lung Cell Mol Physiol. 2012 Jun 8. [Epub ahead of print]
- Horvat SJ, Deshpande DA, Yan H, Panettieri RA, Codina J, Dubose TD Jr, Xin W, Rich TC, Penn RB. A-kinase anchoring proteins regulate compartmentalized cAMP signaling in airway smooth muscle. FASEB J. 2012 May 30. [Epub ahead of print]
- Robinson CB, Leonard J, Panettieri RA Jr. Drug development for severe asthma: What are the metrics? Pharmacol Ther. 2012 May 22. [Epub ahead of print]
- Jude JA, Tirumurugaan KG, Kang BN, Panettieri RA, Walseth TF, Kannan MS. Regulation of CD38 Expression in Human Airway Smooth Muscle Cells: Role of Class I Phosphatidylinositol 3 Kinases. Am J Respir Cell Mol Biol. 2012 May 3.