Profile

The focus of our work is to understand how the reparative function of resident lung mesenchymal stem cells (MSC) is altered during the development and course of lung diseases including pulmonary hypertension, fibrosis and emphysema. In order to define a role for lung MSC in the context of lung disease and their regulation by the microenvironment we employ mouse models. Additionally we use patient derived induced pluripotent stem cells (iPS) as a cell based model to understand molecular changes in which occur in mesenchyme and vascular cell populations as a result of disease specific gene mutations.

 

Our laboratory has identified and characterized lung MSC and demonstrated that these cells are present in the distal lung associated with the microvasculature in both mouse and human tissue. Recent studies in our lab have shown that proper function of the lung MSC is that of an adult angioblast which plays a role in maintaining vascular integrity. Loss of proper MSC function results in loss of tissue integrity and function.

 

There is an increasing emphasis on the development of cell-based therapies to address these conditions, but the lung is a recalcitrant candidate for these strategies because of the diverse cell types and functions as well as a lack of understanding of how chronic disease processes affect stem cell differentiation.   Therefore, prior to testing cell-based therapy, it is desirable to use pre-clinical models of lung injury and chronic disease to determine how changes in the lung tissue during the development of disease affect resident stem cell differentiation and function.

 

 

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Selective depletion of vascular EC-SOD augments chronic hypoxic pulmonary hypertension. Nozik-Grayck E, Woods C, Taylor JM, Benninger RK, Johnson RD, Villegas LR, Stenmark KR, Harrison DG, Majka SM, Irwin D, Farrow KN (2014) Am J Physiol Lung Cell Mol Physiol 307(11): L868-76
    › Primary publication · 25326578 (PubMed) · PMC4254965 (PubMed Central)
  2. ABCG2pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling. Marriott S, Baskir RS, Gaskill C, Menon S, Carrier EJ, Williams J, Talati M, Helm K, Alford CE, Kropski JA, Loyd J, Wheeler L, Johnson J, Austin E, Nozik-Grayck E, Meyrick B, West JD, Klemm DJ, Majka SM (2014) Am J Physiol Cell Physiol 307(8): C684-98
    › Primary publication · 25122876 (PubMed) · PMC4200000 (PubMed Central)
  3. Identification of a common Wnt-associated genetic signature across multiple cell types in pulmonary arterial hypertension. West JD, Austin ED, Gaskill C, Marriott S, Baskir R, Bilousova G, Jean JC, Hemnes AR, Menon S, Bloodworth NC, Fessel JP, Kropski JA, Irwin D, Ware LB, Wheeler L, Hong CC, Meyrick B, Loyd JE, Bowman AB, Ess KC, Klemm DJ, Young PP, Merryman WD, Kotton D, Majka SM (2014) Am J Physiol Cell Physiol 307(5): C415-30
    › Primary publication · 24871858 (PubMed) · PMC4154073 (PubMed Central)
  4. Analysis and isolation of adipocytes by flow cytometry. Majka SM, Miller HL, Helm KM, Acosta AS, Childs CR, Kong R, Klemm DJ (2014) Methods Enzymol : 281-96
    › Primary publication · 24480352 (PubMed) · PMC4143162 (PubMed Central)
  5. Adipose lineage specification of bone marrow-derived myeloid cells. Majka SM, Miller HL, Sullivan T, Erickson PF, Kong R, Weiser-Evans M, Nemenoff R, Moldovan R, Morandi SA, Davis JA, Klemm DJ (2012) Adipocyte 1(4): 215-229
    › Primary publication · 23700536 (PubMed) · PMC3609111 (PubMed Central)
  6. Dysfunctional resident lung mesenchymal stem cells contribute to pulmonary microvascular remodeling. Chow K, Fessel JP, Kaoriihida-Stansbury , Schmidt EP, Gaskill C, Alvarez D, Graham B, Harrison DG, Wagner DH, Nozik-Grayck E, West JD, Klemm DJ, Majka SM (2013) Pulm Circ 3(1): 31-49
    › Primary publication · 23662173 (PubMed) · PMC3641738 (PubMed Central)
  7. The potential for resident lung mesenchymal stem cells to promote functional tissue regeneration: understanding microenvironmental cues. Foronjy RF, Majka SM (2012) Cells 1(4): 874
    › Primary publication · 23626909 (PubMed) · PMC3634590 (PubMed Central)
  8. Critical role for the advanced glycation end-products receptor in pulmonary arterial hypertension etiology. Meloche J, Courchesne A, Barrier M, Carter S, Bisserier M, Paulin R, Lauzon-Joset JF, Breuils-Bonnet S, Tremblay É, Biardel S, Racine C, Courture C, Bonnet P, Majka SM, Deshaies Y, Picard F, Provencher S, Bonnet S (2013) J Am Heart Assoc 2(1): e005157
    › Primary publication · 23525442 (PubMed) · PMC3603259 (PubMed Central)
  9. Free hemoglobin induction of pulmonary vascular disease: evidence for an inflammatory mechanism. Buehler PW, Baek JH, Lisk C, Connor I, Sullivan T, Kominsky D, Majka S, Stenmark KR, Nozik-Grayck E, Bonaventura J, Irwin DC (2012) Am J Physiol Lung Cell Mol Physiol 303(4): L312-26
    › Primary publication · 22728465 (PubMed) · PMC3423829 (PubMed Central)
  10. Attenuated Pik3r1 expression prevents insulin resistance and adipose tissue macrophage accumulation in diet-induced obese mice. McCurdy CE, Schenk S, Holliday MJ, Philp A, Houck JA, Patsouris D, MacLean PS, Majka SM, Klemm DJ, Friedman JE (2012) Diabetes 61(10): 2495-505
    › Primary publication · 22698915 (PubMed) · PMC3447911 (PubMed Central)
  11. Isolation & characterization of Hoechst(low) CD45(negative) mouse lung mesenchymal stem cells. Chow KS, Jun D, Helm KM, Wagner DH, Majka SM (2011) J Vis Exp (56): e3159
    › Primary publication · 22064472 (PubMed) · PMC3227187 (PubMed Central)
  12. Parabronchial smooth muscle constitutes an airway epithelial stem cell niche in the mouse lung after injury. Volckaert T, Dill E, Campbell A, Tiozzo C, Majka S, Bellusci S, De Langhe SP (2011) J Clin Invest 121(11): 4409-19
    › Primary publication · 21985786 (PubMed) · PMC3204843 (PubMed Central)
  13. Osteoblasts derived from induced pluripotent stem cells form calcified structures in scaffolds both in vitro and in vivo. Bilousova G, Jun du H, King KB, De Langhe S, Chick WS, Torchia EC, Chow KS, Klemm DJ, Roop DR, Majka SM (2011) Stem Cells 29(2): 206-16
    › Primary publication · 21732479 (PubMed) · PMC3321731 (PubMed Central)
  14. Physiologic and molecular consequences of endothelial Bmpr2 mutation. Majka S, Hagen M, Blackwell T, Harral J, Johnson JA, Gendron R, Paradis H, Crona D, Loyd JE, Nozik-Grayck E, Stenmark KR, West J (2011) Respir Res : 84
    › Primary publication · 21696628 (PubMed) · PMC3141420 (PubMed Central)
  15. Reduction of reactive oxygen species prevents hypoxia-induced CREB depletion in pulmonary artery smooth muscle cells. Klemm DJ, Majka SM, Crossno JT, Psilas JC, Reusch JE, Garat CV (2011) J Cardiovasc Pharmacol 58(2): 181-91
    › Primary publication · 21562428 (PubMed) · PMC3155008 (PubMed Central)
  16. Concise review: adipocyte origins: weighing the possibilities. Majka SM, Barak Y, Klemm DJ (2011) Stem Cells 29(7): 1034-40
    › Primary publication · 21544899 (PubMed) · PMC3428116 (PubMed Central)
  17. Cell-based therapies in pulmonary hypertension: who, what, and when? Majka S, Burnham E, Stenmark KR (2011) Am J Physiol Lung Cell Mol Physiol 301(1): L9-L11
    › Primary publication · 21515661 (PubMed) · PMC3129904 (PubMed Central)
  18. The pathology of bleomycin-induced fibrosis is associated with loss of resident lung mesenchymal stem cells that regulate effector T-cell proliferation. Jun D, Garat C, West J, Thorn N, Chow K, Cleaver T, Sullivan T, Torchia EC, Childs C, Shade T, Tadjali M, Lara A, Nozik-Grayck E, Malkoski S, Sorrentino B, Meyrick B, Klemm D, Rojas M, Wagner DH, Majka SM (2011) Stem Cells 29(4): 725-35
    › Primary publication · 21312316 (PubMed) · PMC3322548 (PubMed Central)
  19. De novo generation of white adipocytes from the myeloid lineage via mesenchymal intermediates is age, adipose depot, and gender specific. Majka SM, Fox KE, Psilas JC, Helm KM, Childs CR, Acosta AS, Janssen RC, Friedman JE, Woessner BT, Shade TR, Varella-Garcia M, Klemm DJ (2010) Proc Natl Acad Sci U S A 107(33): 14781-6
    › Primary publication · 20679227 (PubMed) · PMC2930432 (PubMed Central)
  20. Lung extracellular superoxide dismutase overexpression lessens bleomycin-induced pulmonary hypertension and vascular remodeling. Van Rheen Z, Fattman C, Domarski S, Majka S, Klemm D, Stenmark KR, Nozik-Grayck E (2011) Am J Respir Cell Mol Biol 44(4): 500-8
    › Primary publication · 20539010 (PubMed) · PMC3095923 (PubMed Central)
  21. Publishing flow cytometry data. Alvarez DF, Helm K, Degregori J, Roederer M, Majka S (2010) Am J Physiol Lung Cell Mol Physiol 298(2): L127-30
    › Primary publication · 19915158 (PubMed) · PMC2822558 (PubMed Central)
  22. Acute lung injury but not sepsis is associated with increased colony formation by peripheral blood mononuclear cells. Burnham EL, Mealer M, Gaydos J, Majka S, Moss M (2010) Am J Respir Cell Mol Biol 43(3): 326-33
    › Primary publication · 19843706 (PubMed) · PMC2933548 (PubMed Central)
  23. Peroxisome proliferator-activated receptor-g agonist treatment increases septation and angiogenesis and decreases airway hyperresponsiveness in a model of experimental neonatal chronic lung disease. Takeda K, Okamoto M, de Langhe S, Dill E, Armstrong M, Reisdorf N, Irwin D, Koster M, Wilder J, Stenmark KR, West J, Klemm D, Gelfand EW, Nozik-Grayck E, Majka SM (2009) Anat Rec (Hoboken) 292(7): 1045-61
    › Primary publication · 19484746 (PubMed) · PMC2873208 (PubMed Central)
  24. A potential role for reactive oxygen species and the HIF-1alpha-VEGF pathway in hypoxia-induced pulmonary vascular leak. Irwin DC, McCord JM, Nozik-Grayck E, Beckly G, Foreman B, Sullivan T, White M, T Crossno J, Bailey D, Flores SC, Majka S, Klemm D, van Patot MC (2009) Free Radic Biol Med 47(1): 55-61
    › Primary publication · 19358884 (PubMed) · PMC2689923 (PubMed Central)
  25. Neovascular capacity of endothelial progenitor cells in the adult pulmonary circulation. Majka S, Alvarez DF (2009) Am J Physiol Lung Cell Mol Physiol 296(6): L868-9
    › Primary publication · 19346436 (PubMed) · PMC4868324 (PubMed Central)
  26. Syndecan-4-expressing muscle progenitor cells in the SP engraft as satellite cells during muscle regeneration. Tanaka KK, Hall JK, Troy AA, Cornelison DD, Majka SM, Olwin BB (2009) Cell Stem Cell 4(3): 217-25
    › Primary publication · 19265661 (PubMed) · PMC3142572 (PubMed Central)
  27. Neprilysin null mice develop exaggerated pulmonary vascular remodeling in response to chronic hypoxia. Dempsey EC, Wick MJ, Karoor V, Barr EJ, Tallman DW, Wehling CA, Walchak SJ, Laudi S, Le M, Oka M, Majka S, Cool CD, Fagan KA, Klemm DJ, Hersh LB, Gerard NP, Gerard C, Miller YE (2009) Am J Pathol 174(3): 782-96
    › Primary publication · 19234135 (PubMed) · PMC2665740 (PubMed Central)
  28. Adult lung side population cells have mesenchymal stem cell potential. Martin J, Helm K, Ruegg P, Varella-Garcia M, Burnham E, Majka S (2008) Cytotherapy 10(2): 140-51
    › Primary publication · 18368593 (PubMed)
  29. Neonatal lung side population cells demonstrate endothelial potential and are altered in response to hyperoxia-induced lung simplification. Irwin D, Helm K, Campbell N, Imamura M, Fagan K, Harral J, Carr M, Young KA, Klemm D, Gebb S, Dempsey EC, West J, Majka S (2007) Am J Physiol Lung Cell Mol Physiol 293(4): L941-51
    › Primary publication · 17693487 (PubMed)
  30. Molecular effects of loss of BMPR2 signaling in smooth muscle in a transgenic mouse model of PAH. Tada Y, Majka S, Carr M, Harral J, Crona D, Kuriyama T, West J (2007) Am J Physiol Lung Cell Mol Physiol 292(6): L1556-63
    › Primary publication · 17369292 (PubMed)
  31. Rosiglitazone promotes development of a novel adipocyte population from bone marrow-derived circulating progenitor cells. Crossno JT, Majka SM, Grazia T, Gill RG, Klemm DJ (2006) J Clin Invest 116(12): 3220-8
    › Primary publication · 17143331 (PubMed) · PMC1679707 (PubMed Central)
  32. Depletion of cAMP-response element-binding protein/ATF1 inhibits adipogenic conversion of 3T3-L1 cells ectopically expressing CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBP beta, or PPAR gamma 2. Fox KE, Fankell DM, Erickson PF, Majka SM, Crossno JT, Klemm DJ (2006) J Biol Chem 281(52): 40341-53
    › Primary publication · 17071615 (PubMed)
  33. Mice deficient in galectin-1 exhibit attenuated physiological responses to chronic hypoxia-induced pulmonary hypertension. Case D, Irwin D, Ivester C, Harral J, Morris K, Imamura M, Roedersheimer M, Patterson A, Carr M, Hagen M, Saavedra M, Crossno J, Young KA, Dempsey EC, Poirier F, West J, Majka S (2007) Am J Physiol Lung Cell Mol Physiol 292(1): L154-64
    › Primary publication · 16951131 (PubMed)
  34. Pleiotropic role of VEGF-A in regulating fetal pulmonary mesenchymal cell turnover. Majka S, Fox K, McGuire B, Crossno J, McGuire P, Izzo A (2006) Am J Physiol Lung Cell Mol Physiol 290(6): L1183-92
    › Primary publication · 16428272 (PubMed)
  35. Identification of novel resident pulmonary stem cells: form and function of the lung side population. Majka SM, Beutz MA, Hagen M, Izzo AA, Voelkel N, Helm KM (2005) Stem Cells 23(8): 1073-81
    › Primary publication · 15987674 (PubMed)
  36. A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of Mycobacterium tuberculosis pulmonary infection. Izzo AA, Izzo LS, Kasimos J, Majka S (2004) Tuberculosis (Edinb) 84(6): 387-96
    › Primary publication · 15525562 (PubMed)
  37. Altered phenotype and reduced function of muscle-derived hematopoietic stem cells. McKinney-Freeman SL, Majka SM, Jackson KA, Norwood K, Hirschi KK, Goodell MA (2003) Exp Hematol 31(9): 806-14
    › Primary publication · 12962727 (PubMed)
  38. Pharmacokinetics of O6-benzylguanine (NSC637037) and its metabolite, 8-oxo-O6-benzylguanine. Tserng KY, Ingalls ST, Boczko EM, Spiro TP, Li X, Majka S, Gerson SL, Willson JK, Hoppel CL (2003) J Clin Pharmacol 43(8): 881-93
    › Primary publication · 12953345 (PubMed)
  39. Cryptococcus neoformans pulmonary granuloma formation is associated with matrix metalloproteinase-2 expression. Majka SM, Kasimos J, Izzo L, Izzo AA (2002) Med Mycol 40(3): 323-8
    › Primary publication · 12146765 (PubMed)
  40. Regulation of matrix metalloproteinase expression by tumor necrosis factor in a murine model of retinal neovascularization. Majka S, McGuire PG, Das A (2002) Invest Ophthalmol Vis Sci 43(1): 260-6
    › Primary publication · 11773040 (PubMed)
  41. Stem cell plasticity in muscle and bone marrow. Goodell MA, Jackson KA, Majka SM, Mi T, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK (2001) Ann N Y Acad Sci : 208-18; discussion 218-20
    › Primary publication · 11458510 (PubMed)
  42. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK, Goodell MA (2001) J Clin Invest 107(11): 1395-402
    › Primary publication · 11390421 (PubMed) · PMC209322 (PubMed Central)
  43. The balance between proteinases and inhibitors in a murine model of proliferative retinopathy. Majka S, McGuire P, Colombo S, Das A (2001) Invest Ophthalmol Vis Sci 42(1): 210-5
    › Primary publication · 11133870 (PubMed)
  44. Hepatocyte growth factor expression in the developing myocardium: evidence for a role in the regulation of the mesenchymal cell phenotype and urokinase expression. Song W, Majka SM, McGuire PG (1999) Dev Dyn 214(1): 92-100
    › Primary publication · 9915579 (PubMed)
  45. Regulation of urokinase expression in the developing avian heart: a role for the Ets-2 transcription factor. Majka SM, McGuire PG (1997) Mech Dev 68(1-2): 127-37
    › Primary publication · 9431810 (PubMed)