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. Adventitial stromal cells and myofibroblasts recruit pro- and anti-inflammatory immune cells in allergic airway inflammation. Xu E, Cao G, Yang Z, Zhang Y, Si Y, Singh K, Jude J, An SS, Koziol-White CJ, Panettieri RA Jr, Yang Q. Allergy. 2023 May 12. PMID: 37171245 DOI: 10.1111/all.15766
2. Obesity elicits a unique metabolomic signature in human airway smooth muscle cells. Shengjie Xu, Nikhil Karmacharya, Gaoyuan Cao, Changjiang Guo, Andrew Gow, Reynold A Panettieri Jr, Joseph A Jude. Am J Physiol Lung Cell Mol Physiol. 2022 Sep 1;323(3):L297-L307. doi: 10.1152/ajplung.00132.2022. Epub 2022 Jul 5.
3. Community- Versus Health Care Organization-Based Approaches to Expanding At-Home COVID-19 Testing in Black and Latino Communities, New Jersey, 2021. 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. Am J Public Health. 2022 Oct 20:e1-e5. doi: 10.2105/AJPH.2022.306989. PMID: 36265092 DOI: 10.2105/AJPH.2022.306989
4. Starving a Cell Promotes Airway Smooth Muscle Relaxation: Inhibition of Glycolysis Attenuates Excitation-Contraction Coupling. Xu S, Karmacharya N, Woo J, Cao G, Guo C, Gow A, Panettieri RA Jr, Jude JA. Am J Respir Cell Mol Biol. 2022 Oct 13. PMID: 36227725DOI: 10.1165/rcmb.2021-0495OC Online ahead of print.
5. Mendelian Randomization Analysis Reveals a Complex Genetic Interplay Among Atopic Dermatitis, Asthma, and GERD. Ahn K, Penn RB, Rattan S, Panettieri RA Jr, Voight BF, An SS. Am J Respir Crit Care Med. 2022 PMID: 36214830 DOI: 10.1164/rccm.202205-0951OC Online ahead of print.
6.  Planning experiments: Updated guidance on experimental design and analysis and their reporting III. 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.  British Journal Pharmacol. 2022 Jun 7. DOI: 10.111/bph.15868. Online ahead of print. PMID: 35673806.
7. Albuterol-Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma. Papi A, Chipps BE, Beasley R, Panettieri RA Jr, Israel E, Cooper M, Dunsire L, Jeynes-Ellis A, Johnsson E, Rees R, Cappelletti C, Albers FC. N Engl J Med. 2022 Jun 2;386(22):2071-2083.  DOI: 10.1056/NEJMoa2203163. Epub 2022 May 15. PMID: 35569035
8. Metabolomics in asthma: A platform for discovery.Xu S, Panettieri RA Jr, Jude J. Mol Aspects Med. 2022 Jun;85:100990. doi: 10.1016/j.mam.2021.100990. Epub 2021 Jul 17. PMID: 34281719.
9. Steroid-induced fibroblast growth factors drive an epithelial-mesenchymal inflammatory axis in severe asthma. Guidi R, Xu D, Choy DF, Ramalingam TR, Lee WP, Modrusan Z, Liang Y, Marsters S, Ashkenazi A, Huynh A, Mills J, Flanagan S, Hambro S, Nunez V, Leong L, Cook A, Tran TH, Austin CD, Cao Y, Clarke C, Panettieri RA Jr, Koziol-White C, Jester WF Jr, Wang F, Wilson MS.Sci Transl Med. 2022 Apr 20;14(641):eabl8146. doi: 10.1126/scitranslmed.abl8146. Epub 2022 Apr 20. PMID: 35442706
10. Identifying a reference list of respiratory sensitizers for the evaluation of novel approaches to study respiratory sensitization. Sadekar N, Boisleve F, Dekant W, Fryer AD, Gerberick GF, Griem P, Hickey C, Krutz NL, Lemke O, Mignatelli C, Panettieri RA Jr., Pinkerton KE, Renskers KJ, Sterchele P, Switalla S, Wolter M, Api AM. Crit Rev Toxicol. 2022 Feb 10;1-13.doi: 10.1080/10408444.2021.2024142. PMID: 35142253.
11. Abil mediates airway smooth muscle cell proliferation and airway remodeling via Jak2/STATE3 signaling. Wang R, Wang Y, Liao G, Chen B, Panettieri RA Jr., Penn RB, Tang DD. iScience. 2022 Jan 29;25(2):103833.doi: 10.1016/j.isci.2022.103833. eCollection 2022 Feb 18. PMID: 35198891. PMCID: PMC8851273.
12. Airway smooth muscle and airway hyperresponsiveness in asthma: mechanisms of airway smooth muscle dysfunction. Ebski EB, Anaspure O, Panettieri RA Jr., Koziol-White CJ. Minerva Med. 2022 Feb;113(1):4-16. DOI: 10.23736/S0026-4806.21.07283-9. Epub 2021 Jan 26. PMID: 33496164.
13. Experiences of Black and Latinx health care workers in support roles during the COVID-19 pandemic: A qualitative study. Rivera-Núñez Z, Jimenez ME, Crabtree BF, Hill D, Pellerano MB, Devance D, Macenat M, Lima D, Gordon M, Sullivan B, Rosati RJ, Ferrante JM, Barrett ES, Blaser MJ, Panettieri RA Jr., Hudson SV. PLoS One. 2022 Jan 18;17(1):e0262606. DOI: 10:1371/journal.pone.0262606. eCollection 2022. PMID: 35041702.
14. Oncostatin M expression induced by bacterial triggers drives airway inflammatory and mucus secretion in severe asthma. Headland SE, Dengler HS, Xu D, Teng G, Everett C, Ratsimandresy RA, Yan D, Kang J, Ganeshan K, Nazarova EV, Gierke S, Wedeles CJ, Guidi R, DePianto DJ, Morshead KB, Huynh A, Mills J, Flanagan S, Hambro Sh, Nunez V, Klementowicz JE, Shi Y, Wang J, Bevers J III, Ramirez-Carrozzi V, Pappu R, Abbas A, Vander-Heiden J, Choy DF, Yadav R, Modrusan Z, Panettieri RA Jr., Koziol-White C, Jester WF Jr., Jenkins BJ, Cao Y, Clarke C, Austin C, Lafkas D, Xu M, Wolters PJ, Arron JR, West NR, Wilson MS. Science Translational Medicine 2022 Jan 12;14(627):eab:f8188. DOI: 10.1126/scitranslmed.abf8188. Epub 2022 Jan 12. PMID: 35020406.
15. STIM1 is a core trigger of airway smooth muscle remodeling and hyperresponsiveness in asthma. Johnson MT,  Xin P, Benson JC, Pathak T, Walter V, Emrich SM, Yoast RE, Zhang X, Cao G, Panettieri RA Jr., Trebak M. PNAS. 2022 Jan 4;119(1):e2114557118. doi: 10.1073/pnas.2114557118. PMID: 34949717.
16. Bronchodilator Responsiveness: An Underappreciated Biomarker for Asthma Exacerbations. Busse WW, Panettieri RA Jr., Corren J. J Allergy Clin Immunol Pract. 2022 Jan;10(1):229-230. doi: 10.1016/j.jaip.2021.10.055. PMID: 35000733.
17. Inhibition of ABCC1 Decreases cAMP Egress and Promotes Human Airway Smooth Muscle Cell Relaxation.  Cao G, Lam H, Jude JA, Karmacharya N, Kan M, Jester W, Koziol-White C, Himes BE, Chupp GL, An SS, Panettieri RA Jr. Am J Respir Cell Mol Biol 2022 Jan;66(1):96-106. DOI: 10.1165/rcmb.2021-0345OC.PMID: 34648729.
18. Autocrine regulation of airwway smooth muscle contraction by diacylglycerol kinase. Yadav SK, Sharma P, Shah SD, Panettieri RA, Kambayashi T, Penn RB, Deshpande DA.J Cell Physiol. 2022 Jan;237(1):603-616. DOI: 10.1002/jcp.30528. Epub 2021 Jul 18. PMID: 34278583.
19. Highly versatile antibody binding assay for the detection of SARS-CoV-2 infection and vaccination. Datta P, Ukey R, Bruiners N, Honnen W, Carayannopoulos MO, Reichman C, Choudhary A, Onyuka A, Handler D, Guerrini V, Mishra PK, Dewald HK, Lardizabal A, Lederer L, Leiser AL, Hussain S, Jagpal SK, Radbel J, Bhowmick T, Horton DB, Barrett ES, Xie YL, Fitzgerald-Bocarsly P, Weiss SH, Woortman M, Parmar H, Roy J, Dominguez-Bello MG, Blaser MJ, Carson JL, Panettieri RA Jr, Libutti SK, Raymond HF, Pinter A, Gennaro ML. J Immunol Methods. 2021 Oct 8:113165. doi: 10.1016/j.jim.2021.113165. Online ahead of print. PMID: 34634317.
20. Diacylglycerol Kinase Inhibition Reduces Airway Contraction by Negative Feedback Regulation of Gq-signaling.  Sharma P, Yadav SK, Shah SD, Javed E, Lim JM, Pan S, Nayak AP, Panettieri RA Jr., Penn RB, Kambayashi T, Deshpande DA. Am J Respir Cell Mol Biol. 2021 Jul 22. doi: 10.1165/rcmb.2021-0106OC. Online ahead of print. PMID: 34293268.
21. Differing perceptions of asthma control and treatment effectiveness by patients with severe asthma and treating subspecialists in the United States. Panettieri RA Jr, Chipps BE, Moore WC, Soong W, Carr WW, Kreindler JL, O’Quinn S, Trudo F, Ambrose CS. J Asthma. 2021 Aug 10:1-13. doi: 10.1080/02770903.2021.1963766. Online ahead of print. PMID: 34374622.
22. Severe asthma exacerbations in the United States: Incidence, characteristics, predictors, and effects of biologic treatments.  Trevor J, Lugogo N, Carr W, Moore WC, Soong W, Panettieri RA Jr,, Desai P, Trudo F, Ambrose CS. Ann Allergy Asthma Immunol. 2021 Nov;127(5):579-587.e1. doi: 10.1016/j.anai.2021.07.010. Epub 2021 Jul 15. PMID: 34273485.
23. Determinants and dynamics of SARS-CoV-2 infection in a diverse population: 6-month evaluation of a prospective cohort study. Horton DB, Barrett ES, Roy J, Gennaro ML, Andrews T, Greenberg P, Bruiners N, Datta P, Ukey R, Velusamy SK, Fine D, Honnen WJ, Yin YS, Pinter A, Brooks A, Tischfield J, Hussain S, Jagpal S, Swaminathan S, Parmar V, Reilly N, Gaur S, Panettieri RA Jr, Carson JL, Blaser MJ.  J Infect Dis. 2021 Aug 13:jiab411. doi: 10.1093/infdis/jiab411. Online ahead of print. PMID: 34387310.
24. Development of a novel, pan-variant aerosol intervention for COVID-19.  Shoemaker RH, Panettieri RA Jr, Libutti SK, Hochster HS, Watts NR, Wingfield PT, Starkl P, Pimenov L, Gawish R, Hladik A, Knapp S, Boring D, White JM, Lawrence Q, Boone J, Marshall JD, Matthews RL, Cholewa BD, Richig JW, Chen BT, McCormick DL, Gugensberger R, Höller S, Penninger JM, Wirnsberger G. bioRxiv. 2021 Sep 14:2021.09.14.459961. doi: 10.1101/2021.09.14.459961. Preprint. PMID: 34545364.
    
25. Editorial policy regarding the citation of preprints in the British Journal of Pharmacology (BJP). George CH, Alexander SPH, Cirino G, Insel PA, Izzo AA, Ji Y, Kendall DA, Panettieri RA, Patel HH, Sobey CG, Stanford SC, Stefanska B, Stephens G, Teixeira M, Ahluwalia A. Br J Pharmacol. 2021 Jul 30. doi: 10.1111/bph.15589. Online ahead of print. PMID: 34328225.