Mission

The program’s mission is to provide resources and expertise in expanding interest in studying the extracellular matrix (ECM) biology. Our long-term goals for the program are to carry out cutting-edge research in biomedical science and foster growth of new and established investigators.

Objectives

The biological role played by matrix protease in lung diseases, vascular problem, cancer and autoimmune disorder is being investigated. The objective of this program is to more fully understand the interplay of the dynamic nature of the ECM in both health and disease.

About our practice

The program is led by Dr. Xin Xu (Program Director). It is a biomedical research hub for a wide variety of research projects on UAB campus and throughout the world. The program consists of physicians, academic scientists, and clinical collaborators to conduct active research protocols. The program is supported by NIH grants as well as funding from other government agencies (i.e. VA) and various Foundations (i.e. ATS, AHA and CF foundation).

The program provides state-of-the-art equipment and technical support for biomedical research. It is equipped with a Flexivent (SCIREQ, Montreal, QB, Canada), smoking machine and chambers (SCIREQ “InExpose” smoking system, SCIREQ, Montreal, QB, Canada), NanoSight, cytokine multiplex Luminex machine, NanoString, GeoMx DSP ,and constructs for the study of matrix tensility. The program provides services at four levels: consultation and experimental design, training clients to use instruments by themselves, running experiments for clients and data analysis, and collaboration. If you are interested in touring Program facility (BBRB808), using the equipment, or visiting with program about potential projects, please contact Dr. Xu at xinxu@uabmc.edu.

Main equipment

The Luminex® 200™ multiplex System

Luminex multiplex assays are driven by xMAP technology, designed to simultaneously detect and quantitate multiple secreted proteins (e.g., cytokines, chemokines, and growth factors) or expressed genes.  The Luminex® 200™ System is a  fast, robust, flow-based analyzer combining three core xMAP® Technologies: the fluorescently dyed micron-sized polystyrene microspheres acting as both the identifier and the solid surface to build the assay; a flow cytometry-based instrument, integrating key xMAP® detection components, and the xPONENT® Software, which is designed for protocol-based data acquisition with robust data regression analysis.The Millipore Milliplex MAP Assay Products,  Invitrogen ProcartaPlex and QuantiGene Plex assays are compatible with Luminex® 200™  instrument platforms.

SCIREQ “InExpose” smoking system (SCIREQ, Montreal, QB, Canada)

This compact inhalation exposure ( inExpose ) is designed to operate under a standard fume hood, and distinguishes itself by its compact size and high level of integration. Its modularity and integration permits both nose-only and/or whole body exposure of rodents, as well as automated generation of cigarette smoke and aerosols. The small form factor reduces direct and indirect costs, and low internal volumes also minimize unintended dilution of precious compounds.

Flexivent (SCIREQ, Montreal, QB, Canada)

The flexiVent is widely regarded as the gold standard for in vivo lung function measurements. It goes beyond traditional resistance and compliance measurements, and captures crucial details about the mechanical properties of conducting airways, terminal airways and parenchyma. The flexiVent achieves the highest sensitivity and reproducibility by precisely controlling experimental conditions.

GeoMx DSP (NanoString , Seattle, WA)

The GeoMx DSP workflow seamlessly integrates with current histology methods to get you robust and reproducible spatial omics data quickly. Stain for RNA or Protein from FFPE or fresh frozen tissue sections, precisely select which tissue compartments or cell types you want to profile based on the biology, and readout expression levels using either the nCounter Analysis System or an Illumina sequencer.

NanoSight (Nanotechnology Ltd, UK)

NaoSight instrument is designed and manufactured by NanoSight Ltd  for the scientific analysis of nanoparticles that are between approximately ten nanometers (nm) and one micron (μm) in diameter. NanoSight instruments are used for a variety of applications, including:

• Ceramic and metallic nanoparticles
• Pigments, paints and sun creams
• Exosomes, microvesicles, outer membrane vesicles, and other small biological particles
• Pharmaceutical particles - liposomes
• Viruses
• Carbon nanotubes (multi-walled)
• Colloidal suspensions and polymer particles
• Cosmetics and foodstuffs
• Particles in fuels and oils (soot, catalyst, wax etc.)
• Wear debris in lubricants
• Chemical Mechanical Polishing Slurries
• Nanotoxicology studies

ManoZoober S60

The NanoZoomer S60 a high-performance digital slide scanner developed by Hamamatsu Photonics, designed for whole slide imaging in both brightfield and fluorescence modes. It accommodates up to 60 slides, supports multi-channel fluorescence, and offers high-resolution scanning at 20× and 40× magnification. With fast scan speeds, Z-stack capability, and compatibility with NDP.view2 software, it’s ideal for pathology, research, and quantitative image analysis workflows.

Others

Cell culture system, Isoflurane Drager Vapor 2000, Microplate Reader (SYNERGY H1) , CytoFLEX S (Beckman Coulter), Sorvall WX80 Plus Ultracentrifuge (Thermo Fisher Scientific, Maximum speed 80,000 rpm), Amersham ImageQuant 800, RT-PCR machine and 405TS Microplate washer.

Selected Publications

Neutrophil elastase-dependent cleavage of LTA4H alters its aminopeptidase activity in cystic fibrosis.
Xu X, Li JD, Green TJ, Wilson L, Genschmer K, Russell D, Blalock JE, Gaggar A. Eur Respir J. 2024 Mar 7;63(3):2301512. doi: 10.1183/13993003.01512-2023. Print 2024 Mar.PMID: 38387968 Free PMC article.

A lactobacilli-based inhaled live biotherapeutic product attenuates pulmonary neutrophilic inflammation.
Nicola T, Wenger N, Xu X, Evans M, Qiao L, Rezonzew G, Yang Y, Jilling T, Margaroli C, Genschmer K, Willis K, Ambalavanan N, Blalock JE, Gaggar A, Lal CV. Nat Commun. 2024 Aug 19;15(1):7113. doi: 10.1038/s41467-024-51169-0.PMID: 39160214 Free PMC article.

Airway extracellular LTA4H concentrations are governed by release from liver hepatocytes and changes in lung vascular permeability.
Mincham KT, Akthar S, Patel DF, Meyer GF, Lloyd CM, Gaggar A, Blalock JE, Snelgrove RJ. Cell Rep. 2024 Aug 27;43(8):114630. doi: 10.1016/j.celrep.2024.114630. Epub 2024 Aug 14.PMID: 39146180 Free article.

Spatial Transcriptomic Approach to Understanding Coronary Atherosclerotic Plaque Stability.
Gastanadui MG, Margaroli C, Litovsky S, Richter RP, Wang D, Xing D, Wells JM, Gaggar A, Nanda V, Patel RP, Payne GA. Arterioscler Thromb Vasc Biol. 2024 Nov;44(11):e264-e276. doi: 10.1161/ATVBAHA.123.320330. Epub 2024 Sep 5.PMID: 39234691 Free article. 

Different-sized extracellular vesicles derived from stored red blood cells package diverse cargoes and cause distinct cellular effects.
Oh JY, Marques MB, Xu X, Li J, Genschmer KR, Phillips E, Chimento MF, Mobley J, Gaggar A, Patel RP. Transfusion. 2023 Mar;63(3):586-600. doi: 10.1111/trf.17271. Epub 2023 Feb 8.PMID: 36752125 Free PMC article.

Protease-armed, Pathogenic Extracellular Vesicles Link Smoking and Chronic Obstructive Pulmonary Disease.
Madison MC, Margaroli C, Genschmer KR, Russell DW, Wells JM, Sari E, Soto-Vazquez YM, Guo YY, Mincham KT, Snelgrove RJ, Gaggar A, Blalock JE. Am J Respir Crit Care Med. 2023 Nov 15;208(10):1115-1125. doi: 10.1164/rccm.202303-0471OC.PMID: 37713301 Free PMC article.

Interferon-dependent signaling is critical for viral clearance in airway neutrophils.
Margaroli C, Fram T, Sharma NS, Patel SB, Tipper J, Robison SW, Russell DW, Fortmann SD, Banday MM, Soto-Vazquez Y, Abdalla T, Saitornuang S, Madison MC, Leal SM Jr, Harrod KS, Erdmann NB, Gaggar A. JCI Insight. 2023 May 22;8(10):e167042. doi: 10.1172/jci.insight.167042.PMID: 37071484 Free PMC article.

Clinical trial of a probiotic and herbal supplement for lung health.
Wenger NM, Qiao L, Nicola T, Nizami Z, Martin I, Halloran BA, Tanaka K, Evans M, Xu X, Dinan TG, Kakilla C, DunnGalvin G, Ambalavanan N, Willis KA, Gaggar A, Lal CV. Front Nutr. 2023 Jun 13;10:1168582. doi: 10.3389/fnut.2023.1168582. eCollection 2023.PMID: 37384109 Free PMC article.

Active transcription in the vascular bed characterizes rapid progression in idiopathic pulmonary fibrosis.
Sharma NS, Patel K, Sari E, Shankar S, Gastanadui MG, Moncada-Giraldo D, Soto-Vazquez Y, Stacks D, Hecker L, Dsouza K, Banday M, O'Neill E, Benson P, Payne G, Margaroli C, Gaggar A. J Clin Invest. 2023 Aug 15;133(16):e165976. doi: 10.1172/JCI165976.PMID: 37384419 Free PMC article. No abstract available. 

Type I interferon-dependent IFIT3 signaling is critical for viral clearance in airway neutrophils.
Margaroli C, Fram T, Sharma NS, Patel SB, Tipper J, Robison SW, Russell DW, Fortmann SD, Banday MM, Abdalla T, Saitornuang S, Madison MC, Leal SM Jr, Harrod KS, Erdmann NB, Gaggar A. Res Sq [Preprint]. 2023 Mar 21:rs.3.rs-1812836. doi: 10.21203/rs.3.rs-1812836/v1.Update in: JCI Insight. 2023 May 22;8(10):e167042. doi: 10.1172/jci.insight.167042.PMID: 36993474 Free PMC article. Preprint.

Therapeutic effect of two strategies directed at disruption of pathogenic neutrophil extracellular vesicles in a murine emphysema model.
Genschmer KR, Madison M, Viera L, Margaroli C, Gaggar A, Blalock JE, Russell DW. Am J Physiol Lung Cell Mol Physiol. 2023 May 1;324(5):L694-L699. doi: 10.1152/ajplung.00057.2023. Epub 2023 Apr 4.PMID: 37014068 Free PMC article. 

Different-sized extracellular vesicles derived from stored red blood cells package diverse cargoes and cause distinct cellular effects.
Oh JY, Marques MB, Xu X, Li J, Genschmer KR, Phillips E, Chimento MF, Mobley J, Gaggar A, Patel RP. Transfusion. 2023 Mar;63(3):586-600. doi: 10.1111/trf.17271. Epub 2023 Feb 8.PMID: 36752125 Free PMC article.

Efficacy of a Probiotic and Herbal Supplement in Models of Lung Inflammation.
Wenger NM, Qiao L, Nicola T, Nizami Z, Xu X, Willis KA, Ambalavanan N, Gaggar A, Lal CV. Microorganisms. 2022 Oct 28;10(11):2136. doi: 10.3390/microorganisms10112136.PMID: 36363728 Free PMC article.

Nontypeable Haemophilus influenzae Redox Recycling of Protein Thiols Promotes Resistance to Oxidative Killing and Bacterial Survival in Biofilms in a Smoke-Related Infection Model.
Hunt BC, Xu X, Gaggar A, Swords WE. mSphere. 2022 Feb 23;7(1):e0084721. doi: 10.1128/msphere.00847-21. Epub 2022 Jan 19.PMID: 35044805 Free PMC article.

A mechanism for matrikine regulation in acute inflammatory lung injury.
Robison SW, Li J, Viera L, Blackburn JP, Patel RP, Blalock JE, Gaggar A, Xu X. JCI Insight. 2021 Apr 8;6(7):e140750. doi: 10.1172/jci.insight.140750.PMID: 33830084 Free PMC article.

Prolyl endopeptidase contributes to early neutrophilic inflammation in acute myocardial transplant rejection.
Payne GA, Sharma NS, Lal CV, Song C, Guo L, Margaroli C, Viera L, Kumar S, Li J, Xing D, Bosley M, Xu X, Wells JM, George JF, Tallaj J, Leesar M, Blalock JE, Gaggar A. JCI Insight. 2021 Mar 22;6(6):e139687. doi: 10.1172/jci.insight.139687.PMID: 33571164 Free PMC article.

Complex genetic encoding of the hepatitis B virus on-drug persistence.
Thai H, Lara J, Xu X, Kitrinos K, Gaggar A, Chan HLY, Xia GL, Ganova-Raeva L, Khudyakov Y. Sci Rep. 2020 Sep 23;10(1):15574. doi: 10.1038/s41598-020-72467-9.PMID: 32968103 Free PMC article.

Haemophilus influenzae persists in biofilm communities in a smoke-exposed ferret model of COPD.
Hunt BC, Stanford D, Xu X, Li J, Gaggar A, Rowe SM, Raju SV, Swords WE. ERJ Open Res. 2020 Aug 11;6(3):00200-2020. doi: 10.1183/23120541.00200-2020. eCollection 2020 Jul.PMID: 32802827 Free PMC article.

Differences in airway microbiome and metabolome of single lung transplant recipients.
Sharma NS, Vestal G, Wille K, Patel KN, Cheng F, Tipparaju S, Tousif S, Banday MM, Xu X, Wilson L, Nair VS, Morrow C, Hayes D Jr, Seyfang A, Barnes S, Deshane JS, Gaggar A. Respir Res. 2020 May 6;21(1):104. doi: 10.1186/s12931-020-01367-3.PMID: 32375889 Free PMC article.

Damage to red blood cells during whole blood storage.
Oh JY, Marques MB, Xu X, Li J, Genschmer K, Gaggar A, Jansen JO, Holcomb JB, Pittet JF, Patel RP. J Trauma Acute Care Surg. 2020 Aug;89(2):344-350. doi: 10.1097/TA.0000000000002730.PMID: 32301878

An Ancient CFTR Ortholog Informs Molecular Evolution in ABC Transporters.
Cui G, Hong J, Chung-Davidson YW, Infield D, Xu X, Li J, Simhaev L, Khazanov N, Stauffer B, Imhoff B, Cottrill K, Blalock JE, Li W, Senderowitz H, Sorscher E, McCarty NA, Gaggar A. Dev Cell. 2019 Nov 18;51(4):421-430.e3. doi: 10.1016/j.devcel.2019.09.017. Epub 2019 Oct 31.PMID: 31679858 Free PMC article.

Neutrophil-targeted, protease-activated pulmonary drug delivery blocks airway and systemic inflammation.
Mejías JC, Forrest OA, Margaroli C, Frey Rubio DA, Viera L, Li J, Xu X, Gaggar A, Tirouvanziam R, Roy K. JCI Insight. 2019 Dec 5;4(23):e131468. doi: 10.1172/jci.insight.131468.PMID: 31661469 Free PMC article.

Effects of hyperoxia on alveolar and pulmonary vascular development in germ-free mice.
Dolma K, Freeman AE, Rezonzew G, Payne GA, Xu X, Jilling T, Blalock JE, Gaggar A, Ambalavanan N, Lal CV. Am J Physiol Lung Cell Mol Physiol. 2020 Feb 1;318(2):L421-L428. doi: 10.1152/ajplung.00316.2019. Epub 2019 Oct 23.PMID: 31644312 Free PMC article.

Benzyloxycarbonyl-proline-prolinal (ZPP): Dual complementary roles for neutrophil inhibition.
Russell DW, Hardison M, Genschmer KR, Szul T, Bratcher PE, Abdul Roda M, Xu X, Viera L, Blalock JE, Gaggar A, Noerager BD. Biochem Biophys Res Commun. 2019 Oct 1;517(4):691-696. doi: 10.1016/j.bbrc.2019.07.111. Epub 2019 Aug 7.PMID: 31400851 Free PMC article.

Proline-Glycine-Proline Peptides Are Critical in the Development of Smoke-induced Emphysema.
Roda MA, Xu X, Abdalla TH, Sadik M, Szul T, Bratcher PE, Viera L, Solomon GM, Wells JM, McNicholas CM, Redegeld FA, Folkerts G, Blalock JE, Gaggar A. Am J Respir Cell Mol Biol. 2019 Nov;61(5):560-566. doi: 10.1165/rcmb.2018-0216OC.PMID: 30958968 Free PMC article.

Activated PMN Exosomes: Pathogenic Entities Causing Matrix Destruction and Disease in the Lung.
Genschmer KR, Russell DW, Lal C, Szul T, Bratcher PE, Noerager BD, Abdul Roda M, Xu X, Rezonzew G, Viera L, Dobosh BS, Margaroli C, Abdalla TH, King RW, McNicholas CM, Wells JM, Dransfield MT, Tirouvanziam R, Gaggar A, Blalock JE.Cell. 2019 Jan 10;176(1-2):113-126.e15. doi: 10.1016/j.cell.2018.12.002.PMID: 30633902 Free PMC article.

An extracellular matrix fragment drives epithelial remodeling and airway hyperresponsiveness.
Patel DF, Peiró T, Shoemark A, Akthar S, Walker SA, Grabiec AM, Jackson PL, Hussell T, Gaggar A, Xu X, Trevor JL, Li J, Steele C, Tavernier G, Blalock JE, Niven RM, Gregory LG, Simpson A, Lloyd CM, Snelgrove RJ. Sci Transl Med. 2018 Aug 22;10(455):eaaq0693. doi: 10.1126/scitranslmed.aaq0693.PMID: 30135247 Free PMC article.

The neutrophil chemoattractant peptide proline-glycine-proline is associated with acute respiratory distress syndrome.
Sharma NS, Lal CV, Li JD, Lou XY, Viera L, Abdallah T, King RW, Sethi J, Kanagarajah P, Restrepo-Jaramillo R, Sales-Conniff A, Wei S, Jackson PL, Blalock JE, Gaggar A, Xu X. Am J Physiol Lung Cell Mol Physiol. 2018 Nov 1;315(5):L653-L661. doi: 10.1152/ajplung.00308.2017. Epub 2018 Aug 9.PMID: 30091378 Free PMC article.

Fibroblast growth factor 23 and Klotho contribute to airway inflammation.
Krick S, Grabner A, Baumlin N, Yanucil C, Helton S, Grosche A, Sailland J, Geraghty P, Viera L, Russell DW, Wells JM, Xu X, Gaggar A, Barnes J, King GD, Campos M, Faul C, Salathe M. Eur Respir J. 2018 Jul 4;52(1):1800236. doi: 10.1183/13993003.00236-2018. Print 2018 Jul.PMID: 29748308 Free PMC article.

Exosomal microRNA predicts and protects against severe bronchopulmonary dysplasia in extremely premature infants.
Lal CV, Olave N, Travers C, Rezonzew G, Dolma K, Simpson A, Halloran B, Aghai Z, Das P, Sharma N, Xu X, Genschmer K, Russell D, Szul T, Yi N, Blalock JE, Gaggar A, Bhandari V, Ambalavanan N. JCI Insight. 2018 Mar 8;3(5):e93994. doi: 10.1172/jci.insight.93994.PMID: 29515035 Free PMC article.

The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection.
Payne GA, Li J, Xu X, Jackson P, Qin H, Pollock DM, Wells JM, Oparil S, Leesar M, Patel RP, Blalock JE, Gaggar A. Sci Rep. 2017 Aug 8;7(1):7563. doi: 10.1038/s41598-017-07610-0.PMID: 28790330 Free PMC article.

Doxycycline improves clinical outcomes during cystic fibrosis exacerbations.
Xu X, Abdalla T, Bratcher PE, Jackson PL, Sabbatini G, Wells JM, Lou XY, Quinn R, Blalock JE, Clancy JP, Gaggar A. Eur Respir J. 2017 Apr 5;49(4):1601102. doi: 10.1183/13993003.01102-2016. Print 2017 Apr.PMID: 28381428 Free article. Clinical Trial.

Ureaplasma infection-mediated release of matrix metalloproteinase-9 and PGP: a novel mechanism of preterm rupture of membranes and chorioamnionitis.
Lal CV, Xu X, Jackson P, Atkinson TP, Faye-Petersen OM, Kandasamy J, Waites K, Biggio JR, Gaggar A, Ambalavanan N. Pediatr Res. 2017 Jan;81(1-1):75-79. doi: 10.1038/pr.2016.176. Epub 2016 Sep 15.PMID: 27632777 Free PMC article.

Protective effect of suppressing STAT3 activity in LPS-induced acute lung injury.
Zhao J, Yu H, Liu Y, Gibson SA, Yan Z, Xu X, Gaggar A, Li PK, Li C, Wei S, Benveniste EN, Qin H. Am J Physiol Lung Cell Mol Physiol. 2016 Nov 1;311(5):L868-L880. doi: 10.1152/ajplung.00281.2016. Epub 2016 Sep 16.PMID: 27638904 Free PMC article. 

Absorbance and redox based approaches for measuring free heme and free hemoglobin in biological matrices.
Oh JY, Hamm J, Xu X, Genschmer K, Zhong M, Lebensburger J, Marques MB, Kerby JD, Pittet JF, Gaggar A, Patel RP. Redox Biol. 2016 Oct;9:167-177. doi: 10.1016/j.redox.2016.08.003. Epub 2016 Aug 10.PMID: 27566280 Free PMC article.