Molecular Nanomechanical Mapping of Histamine-Induced Smooth Muscle Cell Contraction and Shortening.

Rutgers Institute for Translational Medicine and Science
Rutgers, The State University of New Jersey
89 French Street
Suite 4211
New Brunswick, NJ 08901

(732) 235-6404
rp856@rbhs.rutgers.edu

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
Reynold A. Panettieri, Jr, MD, the inaugural Director of the Institute for Translational Medicine and Science and Vice Chancellor for Translational Medicine and Science at Rutgers University, previously served as the Director of the Airways Biology Initiative at the University of Pennsylvania. His interests include 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 patients with chronic severe asthma. Dr. Panettieri’s lab also focuses on cytosolic signaling pathways that mediate gene expression and alter myocyte growth.

Dr. Panettieri also served as the Deputy Director of the Center of Excellence in Environmental Toxicology at the University of Pennsylvania. He directed the human exposure chamber that defines the molecular mechanisms regulating ozone- and particulate matter-induced airway hyperresponsiveness.
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.

• 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.

Selected Publications

1. McDuffie EL, Panettieri RA Jr, Scott CP. G_12/13 signaling in asthma. Respir Res. 2024 Aug 2;25(1):295. doi: 10.1186/ s12931-024-02920-0. PMID: 39095798; PMCID: PMC11297630.
2. Chipps BE, Papi A, Beasley R, Israel E, Panettieri RA Jr, Albers FC, Cooper M, Darken P, Gilbert I, Trudo F, Weinberg M, Cappelletti C. Albuterol- budesonide rescue reduces progression from asthma deterioration to severe exacerbation. J Allergy Clin Immunol Pract. 2024 Jul 2:S2213-2198(24)00678-0. doi: 10.1016/j.jaip.2024.06.037. Epub ahead of print. PMID: 38964735.
3. Koziol-White C, Gebski E, Cao G, Panettieri RA Jr. Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery. Respir Res. 2024 Jun 1;25(1):231. doi: 10.1186/s12931-024-02855-6. PMID: 38824592; PMCID: PMC11144351.
4. Papi A, Chipps BE, Beasley R, Panettieri RA Jr, Israel E, Cooper M, Dunsire L, Jeynes-Ellis A, Rees R, Albers FC, Cappelletti C. Albuterol- budesonide fixed-dose combination rescue inhaler for asthma: a plain language summary of the MANDALA study. Ther Adv Respir Dis. 2024 Jan-Dec;18:17534666241232264. doi:10.1177/17534666241232264. PMID: 38698565; PMCID: PMC11067641.
5. Panettieri R Jr, Lugogo N, Corren J, Ambrose CS. Tezepelumab for Severe Asthma: One Drug Targeting Multiple Disease Pathways and Patient Types. J Asthma Allergy. 2024 Mar 19;17:219-236. doi: 10.2147/JAA.S342391. PMID: 38524099; PMCID: PMC10960583.
6. Koziol-White CJ, Panettieri RA Jr. Editorial for special issue- human precision cut lung slices: an Ex vivo platform for therapeutic target discovery and drug testing in lung disease. Respir Res. 2024 Mar 23;25(1):137. doi:10.1186/s12931-024-02756-8. PMID: 38521949; PMCID: PMC10960987.
7. Papapetropoulos A, Topouzis S, Alexander SPH, Cortese-Krott M, Kendall DA, Martemyanov KA, Mauro C, Nagercoil N, Panettieri RA Jr, Patel HH, Schulz R, Stefanska B, Stephens GJ, Teixeira MM, Vergnolle N, Wang X, Ferdinandy, P. Novel drugs approved by the EMA, the FDA, and the MHRA in 2023: A year in review. Br J Pharmacol. 2024 Jun;181(11):1553-1575. doi: 10.1111/bph.16337. Epub 2024 Mar 22. PMID: 38519837.
8. Panettieri RA Jr, Chipps BE, Skolnik N, George M, Murphy K, Lugogo, N. The Use of Albuterol/Budesonide as Reliever Therapy to Reduce Asthma Exacerbations. J Allergy Clin Immunol Pract. 2024 Apr;12(4):882-888. doi: 10.1016/j.jaip.2024.01.043. Epub 2024 Feb 3. PMID: 38316182.
9. McCormack M, Paczkowski R, Gronroos NN, Noorduyn SG, Lee L, Veeranki P, Johnson MG, Igboekwe E, Kahle-Wrobleski K, Panettieri R. Outcomes of Patients with COPD Treated with ICS/LABA Before and After Initiation of Single- Inhaler Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol (FF/ UMEC/VI). Adv Ther. 2024 Mar;41(3):1245-1261. doi: 10.1007/s12325-023-02776-8. Epub 2024 Feb 4. PMID: 38310193; PMCID: PMC10879256.
10. Pellerano MB, Hill D, Jimenez ME, Gordon M, Macenat M, Ferrante JM, Rivera-Núñez Z, Devance D, Lima D, Sullivan B, Crabtree BF, Georgopoulos P, Barrett ES, Reed DJ, Pernell CT, Dawkins MR, Lynn B, Dixon F, Castañeda M, Garcia H, Blaser MJ, Panettieri RA, Hudson SV. Connect: Cultivating Academic-Community Partnerships to Address Our Communities’ Complex Needs During Public Health Crises. Prog Community Health Partnersh. 2023;17(3):447-464. PMID: 37934443; PMCID: PMC11041973.
11. Bleecker ER, Panettieri RA Jr, Lugogo NL, Corren J, Daizadeh N, Jacob-Nara JA, Deniz Y, Rowe PJ, Khodzhayev A, Soler X, Ferro TJ, Hansen CN. Dupilumab Efficacy in Patients with Type 2 Asthma with and without Elevated Blood Neutrophils. J Immunol Res. 2023 Oct 19;2023:9943584. doi:10.1155/2023/9943584. PMID: 37901346; PMCID: PMC10602700.
12. Spector C, De Sanctis CM, Panettieri RA Jr, Koziol-White CJ. Rhinovirus induces airway remodeling: what are the physiological consequences? Respir Res. 2023 Sep 29;24(1):238. doi: 10.1186/s12931-023-02529-9. PMID: 37773065; PMCID: PMC10540383.
13. Khan NS, Rubin E, McKenna B, Palowitch BL, Sonnenberg F, Argon J, Panettieri RA Jr. The COVID-19 impact on severe uncontrolled asthma costs and biologic use. Allergy Asthma Proc. 2023 Sep 1;44(5):340-344. doi: 10.2500/ aap.2023.44.230045. PMID: 37641228; PMCID: PMC10476494.
14. Nayak AP, Javed E, Villalba DR, Wang Y, Morelli HP, Shah SD, Kim N, Ostrom RS, Panettieri RA Jr, An SS, Tang DD, Penn RB. Prorelaxant E-type Prostanoid Receptors Functionally Partition to Different Procontractile Receptors in Airway Smooth Muscle. Am J Respir Cell Mol Biol. 2023 Nov;69(5):584-591. doi: 10.1165/rcmb.2022-0445OC. PMID: 37523713; PMCID: PMC10633839.
15. Armstrong AJS, Horton DB, Andrews T, Greenberg P, Roy J, Gennaro ML, Carson JL, Panettieri RA, Barrett ES, Blaser MJ. Saliva microbiome in relation to SARS- CoV-2 infection in a prospective cohort of healthy US adults. EBioMedicine. 2023 Aug;94:104731. doi: 10.1016/j.ebiom.2023.104731. Epub 2023 Jul 22. PMID: 37487417; PMCID: PMC10382861.
16. Papapetropoulos A, Alexander SPH, Cortese-Krott M, Kendall DA, Martemyanov K, Mauro C, Panettieri RA Jr, Patel HH, Schulz R, Stefanska B, Stephens GJ, Teixeira MM, Vergnolle N, Wang XJ, Ferdinandy P. Recent changes in the British Journal of Pharmacology: widening scope and improving author and editor experience. Br J Pharmacol. 2023 Sep;180(17):2193-2195. doi: 10.1111/ bph.16169. Epub 2023 Jul 18. PMID: 37462063.
17. O’Halloran JA, Ko ER, Anstrom KJ, Kedar E, McCarthy MW, Panettieri RA Jr, Maillo M, Nunez PS, Lachiewicz AM, Gonzalez C, Smith PB, de Tai SM, Khan A, Lora AJM, Salathe M, Capo G, Gonzalez DR, Patterson TF, Palma C, Ariza H, Lima MP, Blamoun J, Nannini EC, Sprinz E, Mykietiuk A, Alicic R, Rauseo AM, Wolfe CR, Witting B, Wang JP, Parra-Rodriguez L, Der T, Willsey K, Wen J, Silverstein A, O’Brien SM, Al-Khalidi HR, Maldonado MA, Melsheimer R, Ferguson WG, McNulty SE, Zakroysky P, Halabi S, Benjamin DK Jr, Butler S, Atkinson JC, Adam SJ, Chang S, LaVange L, Proschan M, Bozzette SA, Powderly WG; Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial. JAMA. 2023 Jul 25;330(4):328-339. doi: 10.1001/jama.2023.11043. PMID: 37428480; PMCID: PMC10334296.
18. Panettieri RA Jr, Lugogo N, Moore WC, Chipps BE, Jepson B, Zhou W, Ambrose CS, Genofre E, Carstens DD. Real-world effectiveness of benralizumab in US subspecialist-treated adults with severe asthma: Findings from CHRONICLE. Respir Med. 2023 Sep;216:107285. doi: 10.1016/j.rmed.2023.107285. Epub 2023 Jun 7. PMID: 37290579.
19. Siddiqui S, Wenzel SE, Bozik ME, Archibald DG, Dworetzky SI, Mather JL, Killingsworth R, Ghearing N, Schwartz JT, Ochkur SI, Jacobsen EA, Busse WW, Panettieri RA, Prussin C. Safety and Efficacy of Dexpramipexole in Eosinophilic Asthma (EXHALE): A randomized controlled trial. J Allergy Clin Immunol. 2023 Nov;152(5):1121-1130.e10. doi: 10.1016/j.jaci.2023.05.014. Epub 2023 Jun 3. PMID: 37277072.
20. Xu E, Cao G, Yang Z, Zhang Y, Si Y, Singh K, Jude J, An SS, Koziol-White CJ, Panettieri RA Jr, Yang Q. Adventitial stromal cells and myofibroblasts recruit pro- and anti-inflammatory immune cells in allergic airway inflammation. Allergy. 2023 May 12. PMID: 37171245 DOI: 10.1111/all.15766
21. Shengjie Xu, Nikhil Karmacharya, Gaoyuan Cao, Changjiang Guo, Andrew Gow, Reynold A Panettieri Jr, Joseph A Jude. Obesity elicits a unique metabolomic signature in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2022 Sep 1;323(3):L297-L307. doi: 10.1152/ajplung.00132.2022. Epub 2022 Jul
22. Barrett ES, Andrews TR, Roy J, Greenberg P, Ferrante JM, Horton DB, Gordon M, Rivera-Núñez Z, Pellerano MB, Tallia AF, Budolfson M, Georgopoulos P, Reed D, Lynn B, Rosati R, Castañeda M, Dixon F, Pernell C, Hill D, Jimenez ME, Blaser MJ, Panettieri R Jr, Hudson SV. Community- Versus Health Care Organization-Based Approaches to Expanding At-Home COVID-19 Testing in Black and Latino Communities, New Jersey, 2021.Am J Public Health. 2022 Oct 20:e1-e5. doi: 10.2105/AJPH.2022.306989. PMID: 36265092 DOI: 10.2105/AJPH.2022.30698
23. Xu S, Karmacharya N, Woo J, Cao G, Guo C, Gow A, Panettieri RA Jr, Jude JA. Starving a Cell Promotes Airway Smooth Muscle Relaxation: Inhibition of Glycolysis Attenuates Excitation-Contraction Coupling. Am J Respir Cell Mol Biol. 2022 Oct 13. PMID: 36227725DOI: 10.1165/rcmb.2021-0495OC Online ahead of print.
24. Ahn K, Penn RB, Rattan S, Panettieri RA Jr, Voight BF, An SS. Mendelian Randomization Analysis Reveals a Complex Genetic Interplay Among Atopic Dermatitis, Asthma, and GERD. Am J Respir Crit Care Med. 2022 PMID: 36214830 DOI: 10.1164/rccm.202205-0951OC Online ahead of print.
25. Curtis MJ, Alexander SPH, Cirino G, George CH, Dendall DA, Insel PA, Izzo AA, Ji Y, Panettieri RA Jr., Patel HH, Sobey CG, Stanford SC, Stanley P, Stefanska B, Stephens GJ, Teixeira MM, Vergnolle N, Ahluwalia A. Planning experiments: Updated guidance on experimental design and analysis and their reporting III. British Journal Pharmacol. 2022 Jun 7. DOI: 10.111/bph.15868. Online ahead of print. PMID: 35673806.