RESEARCH

Research is the cornerstone of making new discoveries that could positively impact those who suffer from chronic obstructive pulmonary disease (COPD). The Polverino translational research laboratory is dedicated to understanding the pathobiology underlying COPD. Polverino investigators are continually conducting research, discovering new advancements, and leading state-of-the-art studies. Scroll down to see current and past studies performed.  

LAB TECHNIQUES

Imaging: Immunohistochemistry, immunofluorescence, image mass cytometry,  electron, and confocal microscopy, laser capture microdissection, murine lung morphologic assessments of small airway remodeling, airspace enlargement, and mucous metaplasia

Cellular and molecular biology: Flow cytometry, human blood processing and immune cell isolation, human and murine organ digestion, cell culture, DNA and RNA extraction, rt-PCR, western-blot, standard ELISA, multiplex ELISA, ELISPOT, isolation of IgG from plasma, telomere length assay.

Animal models: murine survival and non-survival surgery, murine pulmonary function testings, modeling of cigarette smoke-induced lung damage, unilateral ureter obstruction (UUO), bronchoalveolar lavage

Novel insights into adaptive immunity in COPD

Chronic obstructive pulmonary disease (COPD) is associated with abnormal pulmonary inflammation induced by noxious particles and gases most commonly present in cigarette smoke. In the last few years, activation of adaptive immune responses has emerged as an important event contributing to COPD pathogenesis. We have discovered that B-cell Activating Factor of TNF Family (BAFF), and A Proliferation-inducing Ligand (APRIL), which are key regulators of B-cell homeostasis and proliferation, and the levels of which are increased in several autoimmune diseases, are overexpressed in the peripheral lung of COPD patients. Also, we have discovered that, via BAFF production, B cells trigger a self-perpetuating mechanism of expansion of the B cell pool which is associated with the growth, in number and size, of antibody producing pulmonary lymphoid follicles. Thus, BAFF links COPD to autoimmunity, which opens up new avenues for mechanistic studies and possible therapies for the management of COPD patients. We are now investigating how the adaptive immune system contributes to the development of emphysema in COPD.

Related Publications

Polverino F, Cosio BG, Pons J, Laucho-Contreras M, Tejera P, Iglesias A, Rios A, Jahn A, Sauleda J, Divo M, Pinto-Plata V, Sholl L, Rosas IO, Agustí A, Celli BR, Owen CA. B Cell-Activating Factor. An Orchestrator of Lymphoid Follicles in Severe Chronic Obstructive Pulmonary Disease.Am J Respir Crit Care Med. 2015 Sep 15;192(6):695-705. PMCID: PMC4595676

Polverino F, Baraldo S, Bazzan E, Agostini S, Turato G, LunardiF,Balestro E, Damin M, Papi A, Maestrelli P, CalabreseF, Saetta M. A novel insight into adaptive immunity in COPD: B cell activating factor belonging to the TNF family (BAFF). Am J Respir Crit Care Med. 2010 Oct 15;182(8):1011-9. PMID: 2058117

Polverino F, Laucho-Contreras M, Rojas Quintero J, Divo M, Pinto-Plata V, Sholl L, de-Torres JP, Celli BR, and Owen CA.Increased expression of a proliferation-inducing ligand(APRIL) in lung leukocytes and alveolar epithelial cells in COPD patients with non-small cell lung cancer: A possible link between COPD and lung cancer?Multidiscip Respir Med 2016 Apr 4; 1:17. PMCID: PMC4819280

   

Polverino F, Seys LJ, Bracke KR, Owen CA. B cells in chronic obstructive pulmonary disease: moving to center stage. Am J Physiol Lung Cell Mol Physiol. 2016 Oct 1;311(4):L687-L695. PMCID: PMC5142126

New insight into molecules that regulate COPD

We have published several studies in top-tier journal on the pathogenesis of COPD. First, we have shown for the first time that COPD patients and cigarette smoke (CS)-exposed mice have endothelial injury (EI) associated with increases in tissue oxidative stress- advanced glycation end products (AGEs)- receptor for AGEs (RAGE)-EI pathway in lungs and kidneys. Second, we have discovered the first protective proteinase in COPD: ADisintegrin and A Metalloproteinase Domain-8 (ADAM8), which protects the lung from CS-induced emphysema and mucus metaplasia. Third, we have shown that healthy smokers and COPD patients havereduced airway CC16 and that airway CC16 expression in COPD patients is indirectly related to COPD severity. Fourth,we have shown that Ireb2 promotes from COPD by increasing mitochondrial iron loading, and mitochondrial iron chelation alleviates cigarette smoke-induced lung damage in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD.

Related Publications

Polverino F*, Rojas-Quintero J*, Wang X, Petersen H, Zhang L, Gai X, Hingham A, Zhang D, Rout A, Gupta K, Yambayev I, Pinto-Plata V, Sholl LM, Cunoosamy D, Celli BR, Goldring J, Singh D, Tesfaigzi Y, Wedzicha W, Olsoon H, Owen CA.  A Disintegrin and A Metalloproteinase Domain-8 (ADAM8): A Novel Protective Proteinase in COPD. Am J Respir Crit Care Med 2018 Nov 15;198(10):1254-1267. PMCID: PMC6290938

Polverino F*, Laucho-Contreras M*, Petersen H, Bijol V, Sholl LM, Choi M, Divo M, Pinto-Plata V, Tesfaigzi Y, Celli B, Owen CA. A Pilot Study Linking Endothelial Injury in Lungs and Kidneys in COPD. Am J Respir Crit Care Med. 2017. Jun 1;195(11):1464-1476. PMCID: PMC5470750

Laucho-Contreras M*, Polverino F*, Gupta K, Taylor K, Kelly E, Pinto-Plata V, Divo M, Ashfaq N, Petersen H, Stripp B, Pilon AL, Tesfaigzi Y, Celli B, Owen CA. Protective role for club cell secretory protein-16 (CC16) in the development of COPD. Eur Respir J. 2015 Jun;45(6):1544-56. PMCID: PMC4451404

Cloonan SM, Glass K, Laucho-Contreras ME, Bhashyam AR, Cervo M, Pabón MA, Konrad C, Polverino F, Siempos II, Perez E, Mizumura K, Ghosh MC, Parameswaran H, Williams NC, Rooney KT, Chen ZH, Goldklang MP, Yuan GC, Moore SC, Demeo DL, Rouault TA, D'Armiento JM, Schon EA, Manfredi G, Quackenbush J, Mahmood A, Silverman EK, Owen CA, Choi AM. Mitochondrial iron chelation ameliorates cigarette smoke-induced bronchitis and emphysema in mice. Nat Med. 2016 Feb;22(2):163-74. PMCID: PMC4742374

First model of cigarette smoke-induced airway disease in non-human primates

We investigated the utility of cigarette smoke (CS)-exposed cynomolgus macaque non-human primates (NHPs) as a larger animal model of COPD. NHPs exposed to CS for 12 weeks develop robust airway pathologies including small airway remodeling, mucus metaplasia, and increases in the size and number of submucosal glands. While NHPs exposed to CS for 12 weeks do not develop emphysema, they do develop pathologies that contribute to this process (pulmonary inflammation, alveolar septal cell apoptosis, increases in lung oxidative stress levels, and increased in pulmonary lymphoid follicles). Unlike rodents, NHPs can safely undergo longitudinal sampling, which could be useful for assessing novel biomarkers or therapeutics for COPD.

Related Publications

Polverino F, Doyle-Eisele M, McDonald J, Kelly EM, Wilder J, Royer C, Laucho-Contreras M, Mauderly J, Divo M, Pinto-Plata V, Celli BR, Tesfaigzi Y, Owen CA. A Novel Non-Human Primate Model of Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease. Am. J. Pathol. 2015 Mar;185(3):741-55. PMCID: PMC4348468

Polverino F, Doyle-Eisele M, McDonald J, Kelly EM, Wilder J, Mauderly J, Divo M, Pinto-Plata V, Celli BR, Tesfaigzi Y, Owen CA. A Novel Non-Human Primate Model of Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease. Eur Respir J 2014; 44: Suppl. 58, 864 (Abstract).

Polverino F, Doyle-Eisele M, McDonald J, Kelly EM, Wilder J, Royer C, Laucho-Contreras M, Mauderly J, Divo M, Pinto-Plata V, Celli BR, Tesfaigzi Y, Owen CA. A Novel Non-Human Primate Model of Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease. Am. J. Pathol. 2015 Mar;185(3):741-55. PMCID: PMC4348468

New clinical insight into COPD

We have published several clinical studies focused on COPD pathophysiology and clinical observations. We have analyzed the factors determining the early onset of COPD in the Lovelace Smokers Cohort, and found that low lung function and rapid decline of lung function of 40 ml/year might help detect those smokers at the highest risk of incident COPD. With the BODE Collaborative group, we have assessed the differences between 2015 and 2017 GOLD guidelines. Compared with 2015, the GOLD ABCD 2017 classification significantly shifts patients from grades C and D to categories A and B. The GOLD 2017 equalize the Charlson comorbidity score in all groups and minimizes the differences in BODE between groups B and D, making the risk of death similar between them. We have also shown that dietary supplementation with CoQ10 and Creatine improves functional performance, body composition and perception of dyspnea in patients with COPD.

Related Publications

Petersen H, Sood A, Polverino F, Owen CA, Pinto-Plata V, Celli BR, Tesfaigzi Y.The Course of Lung Function in Middle-aged Heavy Smokers: Incidence and Time to Early Onset of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2018 Dec 1;198(11):1449-1451. PMCID: PMC6290951

 

Cabrera López C, Casanova Macario C, Marín Trigo JM, de-Torres JP, Sicilia Torres R, González JM, Polverino F, Divo M, Pinto Plata V, Zulueta JJ, Celli B. Comparison of the 2017 and 2015 Global Initiative for Chronic Obstructive Lung Disease Reports. Impact on Grouping and Outcomes. Am J Respir Crit Care Med. 2018 Feb 15;197(4):463-469. PMID: 29099607

 

De Benedetto F, Pastorelli R, Ferrario M, de Blasio F, Marinari S, Brunelli L, Wouters EFM, Polverino F, Celli BR. Supplementation with Qter® and Creatine improves functional performance in COPD patients on long term oxygen therapy. Respir Med. 2018 Sep;142:86-93. PMID: 30170808

 

Polverino F, Celli B. The Challenge of Controlling the COPD Epidemic: Unmet Needs. Am J Med. 2018 Sep;131(9S):1-6. PMID: 29778456

RESEARCH STUDIES

 RESEARCH SUPPORT

Ongoing Research Support

Flight Attendants Medical Research Institute

Parker B. Francis Foundation

Completed Research Support

Flight Attendants Medical Research Institute

American Lung Association

Department of Defense

The Polverino Laboratory

© 2019 by The Polverino Transitional Research Laboratory. 

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