大象传媒

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Matthew Markovetz, PhD

Research Associate

Specialty Areas:

Mucus biophysics and liquid and ion transport that regulate mucus properties and clearance

Chronology:

BS, Chemical and Biological Engineering, University of Colorado at Boulder (2012).

PhD, Chemical Engineering, University of Pittsburgh (2016).

Postdoctoral Fellow, Cystic Fibrosis and Pulmonary Research Center, University of North Carolina at Chapel Hill (2017-2020).

Research Associate, Cystic Fibrosis and Pulmonary Research Center, University of North Carolina at Chapel Hill (2020-present).

Research Focus:

Mucus serves as a protective barrier at the interface of all 鈥渨et鈥� epithelia. Whether in the reproductive and GI tracts, the eyes, or the respiratory system 鈥� including the lung, which is our primary organ of focus 鈥� mucus functions to protect the epithelium from harmful elements like toxins and pathogens. From a basic science perspective, mucus is a biopolymeric gel composed of thousands of different components, but the primary biopolymers that regulate its properties are a class of extraordinarily large and long proteins called mucins. In the lung specifically, mucus composed mostly of the mucin MUC5B traps inhaled pathogens and particulate matter, preventing their access to airway cells while the mucus is efficiently transported up and out of the airways by way of ciliary action. This mucociliary clearance (MCC) system is critical to health, and defects in any of its individual components can cause disease. For example, primary ciliary dyskinesia results from defective or absent ciliary action. With regard to our research in mucus, the airway pathology of cystic fibrosis (CF) is characterized by the accumulation of mucus that becomes abnormally sticky and viscous. In fact, CF has also been referred to historically as mucoviscidosis of the lung. Asthma and COPD are also noteworthy diseases that feature mucus abnormalities.

In the case of CF, mucus becomes hyperviscous because its components become hyperconcentrated due to the dysfunctional or absent chloride water secretion caused by a mutation in the cystic fibrosis transmembrane conductance regulator protein. In particular, levels of MUC5B and its inflammatory counterpart MUC5AC become elevated and proportionately more MUC5AC is produced. This induces a feedback cycle of inflammation and further mucus production, which in the absence of liquid secretion, leads to MCC failure and airway obstruction. In our lab, we characterize how these changes in mucus concentration and composition affect its biophysical properties through rheological studies at the macro and microscale. By studying the effect of concentration on viscoelasticity we are able to predict the extent to which hyperconcentration affects MCC negatively and propose and study therapeutic pathways that may decrease the mucus burden on the MCC system. Similarly, we are able to study how therapeutics that aim to break up the chemical linkages with the mucus gel may also affect the viscoelasticity and clearability of mucus. Furthermore, by applying fundamental mathematical and engineering perspectives toward the study of mucus, we are able to robustly characterize mucus despite the heterogeneities inherent to most mucus sample types and their means of acquisition. Ultimately we seek to provide translational knowledge regarding the fundamental behavior of mucus as polymer gel to how it affects human health and disease.

Selected Bibliography:

  1. Fazelpour F, Hill LC, Markovetz MR, Hill DB. . Annu Rev Anal Chem (Palo Alto Calif). 2025 Feb 14. doi: 10.1146/annurev-anchem-061622-015821. Epub ahead of print. PMID: 39952642.
  2. Greenwald MA, Meinig SL, Plott LM, Roca C, Higgs MG, Vitko NP, Markovetz MR, Rouillard KR, Carpenter J, Kesimer M, Hill DB, Schisler JC, Wolfgang MC. . mBio. 2024 Jun 12;15(6):e0345123. doi: 10.1128/mbio.03451-23. PMID: 38651896. PMCID: PMC11237767.
  3. Dougherty GW, Ostrowski LE, N枚the-Menchen T, Raidt J, Schramm A, Olbrich H, Yin W, Sears PR, Dang H, Smith AJ, Beule AG, Hjeij R, Rutjes N, Haarman EG, Maas SM, Ferkol TW, Noone PG, Olivier KN, Bracht DC, Barbry P, Zaragosi LE, Fierville M, Kliesch S, Wohlgemuth K, K枚nig J, George S, Loges NT, Ceppe A, Markovetz MR, Luo H, Guo T, Rizk H, Eldesoky T, Dahlke K, Boldt K, Ueffing M, Hill DB, Pang YP, Knowles MR, Zariwala MA, Omran H. . Am J Respir Crit Care Med. 2024 Jul 1;210(1):63-76. doi: 10.1164/rccm.202308-1370OC. PMID: 38626355. PMCID: PMC11197063.
  4. Rouillard KR, Esther CP, Kissner WJ, Plott LM, Bowman DW, Markovetz MR, Hill DB. . PLoS One. 2024 Feb 23;19(2):e0294120. doi: 10.1371/journal.pone.0294120. PMID: 38394229; PMCID: PMC10890754.
  5. Donoghue LJ, Markovetz MR, Morrison CB, Chen G, McFadden KM, Sadritabrizi T, Gutay MI, Kato T, Rogers TD, Snead JY, Livraghi-Butrico A, Button B, Ehre C, Grubb BR, Hill DB, Kelada SNP. . Am J Physiol Lung Cell Mol Physiol. 2023 Dec 1;325(6):L765-L775. doi: 10.1152/ajplung.00390.2022. PMID: 37847709. PMCID: PMC11068428.
  6. Ozeri-Galai E, Friedman L, Barchad-Avitzur O, Markovetz MR, Boone W, Rouillard KR, Stampfer CD, Oren YS, Hill DB, Kerem B, Hart G. . Nucleic Acid Ther. 2023 Oct;33(5):306-318. doi: 10.1089/nat.2023.0015. PMID: 37643307.
  7. Markovetz MR, Hibbard JE, Plott LM, Bacudio LG, Kissner WJ, Ghio A, Kumar PA, Arora H, Hill DB. . Front Physiol. 2023 Mar 10;14:1111647. doi: 10.3389/fphys.2023.1111647. PMID: 36969580; PMCID: PMC10036356.
  8. Rouillard KR, Markovetz MR, Kissner WJ, Boone WL, Plott LM, Hill DB. . Biofilm. 2023 Jan 21;5:100104. doi: 10.1016/j.bioflm.2023.100104. PMID: 36711323; PMCID: PMC9880403.
  9. Markovetz MR, Garbarine IC, Morrison CB, Kissner WJ, Seim I, Forest MG, Papanikolas MJ, Freeman R, Ceppe A, Ghio A, Alexis NE, Stick SM, Ehre C, Boucher RC, Esther CR, Muhlebach MS, Hill DB.聽. J Cyst Fibros.聽2022 Nov;21(6):959-966. doi: 10.1016/j.jcf.2022.04.008. PMID: 35437233.
  10. Rouillard KR, Kissner WJ, Markovetz MR, Hill DB. . mSphere. 2022 Aug 31;7(4):e0029122. doi: 10.1128/msphere.00291-22. PMID: 35968965; PMCID: PMC9429933.
  11. Wykoff JA, Shaffer KM, Araba KC, Markovetz MR, Patarin J, Robert de Saint Vincent M, Donaldson SH, Ehre C. . J Vis Exp. 2022 Apr 21;(182). doi: 10.3791/63876. PMID: 35532240.
  12. Kato T, Radicioni G, Papanikolas MJ, Stoychev GV, Markovetz MR, Aoki K, Porterfield M, Okuda K, Barbosa Cardenas SM, Gilmore RC, Morrison CB, Ehre C, Burns KA, White KK, Brennan TA, Goodell HP, Thacker H, Loznev HT, Forsberg LJ, Nagase T, Rubinstein M, Randell SH, Tiemeyer M, Hill DB, Kesimer M, O’Neal WK, Ballard ST, Freeman R, Button B, Boucher RC. . Sci Adv. 2022 Apr;8(13):eabm9718. doi: 10.1126/sciadv.abm9718. PMID: 35363522.
  13. Morrison CB, Shaffer KM, Araba KC, Markovetz MR, Wykoff JA, Quinney NL, Hao S, Delion MF, Flen AL, Morton LC, Liao J, Hill DB, Drumm ML, O’Neal WK, Kesimer M, Gentzsch M, Ehre C. . Eur Respir J. 2022 Feb 3;59(2):2100185. doi: 10.1183/13993003.00185-2021. PMID: 34172469. PMCID: PMC8859811.
  14. Ford AG, Cao XZ, Papanikolas MJ, Kato T, Boucher RC, Markovetz MR, Hill DB, Freeman R, Forest MG. . Stud Appl Math. 2021 Nov;147(4):1369-1387. doi: 10.1111/sapm.12433. PMID: 35221375; PMCID: PMC8871504.
  15. Sears PR, Bustamante-Marin XM, Gong H, Markovetz MR, Superfine R, Hill DB, Ostrowski LE. . Biophys J. 2021 Apr 20;120(8):1387-1395. doi: 10.1016/j.bpj.2021.01.041. PMID: 33705757. PMCID: PMC8105732.
  16. Rouillard KR, Markovetz MR, Bacudio LG, Hill DB, Schoenfisch MH. . ACS Infect Dis. 2020 Jul 10;6(7):1940-1950. doi: 10.1021/acsinfecdis.0c00246. PMID: 32510928.
  17. Morrison CB, Markovetz MR, Ehre C. . Pediatr Pulmonol. 2019 Nov;54 Suppl 3(Suppl 3):S84-S96. doi: 10.1002/ppul.24530. PMID: 31715083; PMCID: PMC6853602.
  18. Markovetz M, Subramani D, Kissner W, Morrison C, Garbarine I, Ghio A, Ramsey K, Arora H, Kumar P, Nix D, Kumagai T, Krunkosky T, KrauseD , Radicioni G, Alexis N, Kesimer M, Tiemeyer M, Boucher RC, Ehre C, Hill D. . Am J Physiol Lung Cell Mol Physiol. 2019 Oct 1;317(4):L498-L509. doi: 10.1152/ajplung.00238.2019. PMID: 31389736. PMCID: PMC6842913.
  19. Esther CR Jr, Muhlebach MS, Ehre C, Hill DB, Wolfgang MC, Kesimer M, Ramsey KA, Markovetz MR, Garbarine IC, Forest MG, Seim I, Zorn B, Morrison CB, Delion MF, Thelin WR, Villalon D, Sabeter JR, Turkovic L, Ranganathan S, Stick SM, Boucher RC, on behalf of AREST CF. . Sci Transl Med. 2019 Apr 3;11(486). doi: 10.1126/scitranslmed.aav3488. PMID: 30944166. PMCID: PMC6566903.
  20. Ehre C, Rushton ZL, Wang B, Hothem LN, Morrison CB, Fontana NC, Markovetz MR, Delion MF, Kato T, Villalon D, Thelin WR, Esther CR Jr., Hill DB, Grubb BR, Livraghi-Butrico A, Donaldson SH, Boucher RC. . Am J Respir Crit Care Med. 2019 Jan 15;199(2):171-180. doi: 10.1164/rccm.201802-0245OC. PMID: 30212240. PMCID: PMC6353008.
  21. Hancock LA, Hennessy CE, Solomon GM, Dobrinskikh E, Estrella A, Hara N, Hill DB, Kissner WJ, Markovetz MR, Grove Villalon DE, Voss ME, Tearney GJ, Carroll KS, Shi Y, Schwarz MI, Thelin WR, Rowe SM, Yang IV, Evans CM, Schwartz DA. . Nat Commun. 2018 Dec 18;9(1):5363. doi: 10.1038/s41467-018-07768-9. PMID: 30560893; PMCID: PMC6299094.
  22. Hill DB, Long RF, Kissner WJ, Atieh E, Garbarine IC, Markovetz MR, Fontana NC, Christy M, Habibpour M, Tarran R, Forest MG, Boucher RC, Button B. . Eur Respir J. 2018 Dec 6;52(6). doi: 10.1183/13993003.01297-2018. PMID: 30361244. PMCID: PMC6446239.
  23. Corcoran TE, Godovchik JE, Donn KH, Busick DR, Goralski J, Locke LW, Markovetz MR, Myerburg MM, Muthukrishnan A, Weber L, Lacy RT, Pilewski JM. . Pediatr Pulmonol. 2017 Sep;52(9):1142-1149. doi: 10.1002/ppul.23749. PMID: 28737262; PMCID: PMC5561478.
  24. Locke LW, Myerburg MM, Weiner DJ, Markovetz MR, Parker RS, Muthukrishnan A, Weber L, Czachowski MR, Lacy RT, Pilewski JM, Corcoran TE. . Eur Respir J. 2016 May;47(5):1392-401. doi: 10.1183/13993003.01880-2015. PMID: 27009167; PMCID: PMC5516211.
  25. Markovetz MR, Corcoran TE, Locke LW, Myerburg MM, Pilewski JM, Parker RS.. PLoS One. 2014 Nov 10;9(11):e111972. doi: 10.1371/journal.pone.0111972. PMID: 25383714; PMCID: PMC4226497.
  26. Locke LW, Myerburg MM, Markovetz MR, Parker RS, Weber L, Czachowski MR, Harding TJ, Brown SL, Nero JA, Pilewski JM, Corcoran TE. . Eur Respir J. 2014 Sep;44(3):675-84. doi: 10.1183/09031936.00220513. PMID: 24743971; PMCID: PMC4150848.
Headshot of Matthew Markovetz