Claude Chapman, PhD
Professor
Medicine
School of Medicine

Despite the detection of senescent AECIIs in fibrotic lungs, their role in fibrogenesis is unknown and their secretory phenotype (SASP) remains undefined. In addition, senescent fibroblasts have also been detected in pulmonary fibrotic tissue. Interestingly, unlike many organs where the fibrosis never resolves, dermal fibrosis can undergo spontaneous regression despite the constant detection of senescent fibroblasts. We, therefore, hypothesize that the dynamic changes in the SASP from profibrotic to pro-resolution occurs in skin but not in lungs resulting in fibrosis reversal only in the skin. Using transgenic mouse strains and pharmacological senolytic treatment, we will determine how Sn cells have the potential to regulate fibrogenesis and its resolution by switching their SASP factors expression over time. Our findings will have important implications for how emerging senolytic drugs, which have the potential to provide novel therapeutic benefits for the treatment of SSc, should best be administered.

• Secretion of leukotrienes by senescent lung fibroblasts promotes pulmonary fibrosis.
  JCI insight 2019 Wiley CD, Brumwell AN, Davis SS, Jackson JR, Valdovinos A, Calhoun C, Alimirah F, Castellanos CA, Ruan R, Wei Y, Chapman HA, Ramanathan A, Campisi J, Jourdan Le Saux C
• Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition.
  Nature communications 2019 Pereira BI, Devine OP, Vukmanovic-Stejic M, Chambers ES, Subramanian P, Patel N, Virasami A, Sebire NJ, Kinsler V, Valdovinos A, LeSaux CJ, Passos JF, Antoniou A, Rustin MHA, Campisi J, Akbar AN
• Idiopathic Pulmonary Fibrosis: Cell Death and Inflammation Revisited.
  American journal of respiratory cell and molecular biology 2018 Le Saux CJ, Chapman HA
• Fibroblast-specific inhibition of TGF-β1 signaling attenuates lung and tumor fibrosis.
  The Journal of clinical investigation 2017 Wei Y, Kim TJ, Peng DH, Duan D, Gibbons DL, Yamauchi M, Jackson JR, Le Saux CJ, Calhoun C, Peters J, Derynck R, Backes BJ, Chapman HA
• Differences in forward angular light scattering distributions between M1 and M2 macrophages.
  Journal of biomedical optics 2015 Halaney DL, Zahedivash A, Phipps JE, Wang T, Dwelle J, Saux CJ, Asmis R, Milner TE, Feldman MD
• Calpastatin overexpression impairs postinfarct scar healing in mice by compromising reparative immune cell recruitment and activation.
  American journal of physiology. Heart and circulatory physiology 2015 Wan F, Letavernier E, Le Saux CJ, Houssaini A, Abid S, Czibik G, Sawaki D, Marcos E, Dubois-Rande JL, Baud L, Adnot S, Derumeaux G, Gellen B
• Women and Lung Disease. Sex Differences and Global Health Disparities.
  American journal of respiratory and critical care medicine 2015 Pinkerton KE, Harbaugh M, Han MK, Jourdan Le Saux C, Van Winkle LS, Martin WJ, Kosgei RJ, Carter EJ, Sitkin N, Smiley-Jewell SM, George M
• Myocardial tissue caveolae.
  Comprehensive Physiology 2015 Sanon VP, Sawaki D, Mjaatvedt CH, Jourdan-Le Saux C
• SMAD-independent down-regulation of caveolin-1 by TGF-β: effects on proliferation and survival of myofibroblasts.
  PloS one 2015 Sanders YY, Cui Z, Le Saux CJ, Horowitz JC, Rangarajan S, Kurundkar A, Antony VB, Thannickal VJ
• Senescent Cells Contribute to the Physiological Remodeling of Aged Lungs.
  The journals of gerontology. Series A, Biological sciences and medical sciences 2015 Calhoun C, Shivshankar P, Saker M, Sloane LB, Livi CB, Sharp ZD, Orihuela CJ, Adnot S, White ES, Richardson A, Le Saux CJ
• Streptococcus pneumoniae translocates into the myocardium and forms unique microlesions that disrupt cardiac function.
  PLoS pathogens 2014 Brown AO, Mann B, Gao G, Hankins JS, Humann J, Giardina J, Faverio P, Restrepo MI, Halade GV, Mortensen EM, Lindsey ML, Hanes M, Happel KI, Nelson S, Bagby GJ, Lorent JA, Cardinal P, Granados R, …
• Caveolin-1 deletion exacerbates cardiac interstitial fibrosis by promoting M2 macrophage activation in mice after myocardial infarction.
  Journal of molecular and cellular cardiology 2014 Shivshankar P, Halade GV, Calhoun C, Escobar GP, Mehr AJ, Jimenez F, Martinez C, Bhatnagar H, Mjaatvedt CH, Lindsey ML, Le Saux CJ
• Mycoplasma pneumoniae CARDS toxin exacerbates ovalbumin-induced asthma-like inflammation in BALB/c mice.
  PloS one 2014 Medina JL, Coalson JJ, Brooks EG, Le Saux CJ, Winter VT, Chaparro A, Principe MF, Solis L, Kannan TR, Baseman JB, Dube PH
• Role of caveolin-1 in asthma and chronic inflammatory respiratory diseases.
  Expert review of respiratory medicine 2014 Royce SG, Le Saux CJ
• Colony-stimulating factor 1 potentiates lung cancer bone metastasis.
  Laboratory investigation; a journal of technical methods and pathology 2014 Hung JY, Horn D, Woodruff K, Prihoda T, LeSaux C, Peters J, Tio F, Abboud-Werner SL
• Airway hyperresponsiveness is associated with airway remodeling but not inflammation in aging Cav1-/- mice.
  Respiratory research 2013 Gabehart KE, Royce SG, Maselli DJ, Miyasato SK, Davis EC, Tang ML, Jourdan Le Saux C
• A novel telomerase activator suppresses lung damage in a murine model of idiopathic pulmonary fibrosis.
  PloS one 2013 Le Saux CJ, Davy P, Brampton C, Ahuja SS, Fauce S, Shivshankar P, Nguyen H, Ramaseshan M, Tressler R, Pirot Z, Harley CB, Allsopp R
• Chronic and intermittent hypoxia differentially regulate left ventricular inflammatory and extracellular matrix responses.
  Hypertension research : official journal of the Japanese Society of Hypertension 2012 Ramirez TA, Jourdan-Le Saux C, Joy A, Zhang J, Dai Q, Mifflin S, Lindsey ML
• Caveolin-1 deficiency protects from pulmonary fibrosis by modulating epithelial cell senescence in mice.
  American journal of respiratory cell and molecular biology 2012 Shivshankar P, Brampton C, Miyasato S, Kasper M, Thannickal VJ, Le Saux CJ
• Cellular senescence increases expression of bacterial ligands in the lungs and is positively correlated with increased susceptibility to pneumococcal pneumonia.
  Aging cell 2011 Shivshankar P, Boyd AR, Le Saux CJ, Yeh IT, Orihuela CJ
• Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling.
  Matrix biology : journal of the International Society for Matrix Biology 2011 Miyasato SK, Loeffler J, Shohet R, Zhang J, Lindsey M, Le Saux CJ
• Extracellular matrix roles during cardiac repair.
  Life sciences 2010 Jourdan-Lesaux C, Zhang J, Lindsey ML
• The role of caveolin-1 in pulmonary matrix remodeling and mechanical properties.
  American journal of physiology. Lung cellular and molecular physiology 2008 Le Saux O, Teeters K, Miyasato S, Choi J, Nakamatsu G, Richardson JA, Starcher B, Davis EC, Tam EK, Jourdan-Le Saux C
• Down-regulation of caveolin-1, an inhibitor of transforming growth factor-beta signaling, in acute allergen-induced airway remodeling.
  The Journal of biological chemistry 2007 Le Saux CJ, Teeters K, Miyasato SK, Hoffmann PR, Bollt O, Douet V, Shohet RV, Broide DH, Tam EK
• A role for dietary selenium and selenoproteins in allergic airway inflammation.
  Journal of immunology (Baltimore, Md. : 1950) 2007 Hoffmann PR, Jourdan-Le Saux C, Hoffmann FW, Chang PS, Bollt O, He Q, Tam EK, Berry MJ
• A new approach for analyzing cellular infiltration during allergic airway inflammation.
  Journal of immunological methods 2007 Hoffmann PR, Gurary A, Hoffmann FW, Jourdan-Le Saux C, Teeters K, Hashimoto AC, Tam EK, Berry MJ
• Oral health disparities and periodontal disease in Asian and Pacific Island populations.
  Ethnicity & disease 2005 Harrigan RC, Easa D, LeSaux C, Millar L, Kagihara LE, Shomaker TS, Greer MH, Beck JD, Offenbacher S
• Progressive hair loss and myocardial degeneration in rough coat mice: reduced lysyl oxidase-like (LOXL) in the skin and heart.
  The Journal of investigative dermatology 2004 Hayashi K, Cao T, Passmore H, Jourdan-Le Saux C, Fogelgren B, Khan S, Hornstra I, Kim Y, Hayashi M, Csiszar K
• Polymorphisms in the interleukin-4 receptor alpha chain: association with traits of allergy and asthma in an admixed population in Hawaii.
  Cellular and molecular biology (Noisy-le-Grand, France) 2003 Tam EK, Jourdan-LeSaux C, Stauder S, Bollt O, Reber B, Yamamoto F, Haymer D
• A base substitution in the interleukin-10 (IL-10) promoter between Sp1 and ets-1 binding sites is not associated with variation of IL-10 levels.
  Cellular and molecular biology (Noisy-le-Grand, France) 2003 Jourdan-Le Saux C, Bollt O, Orozco C, Concepcion J, Yamaga K, Yamamoto F, Haymer D, Tam EK
• Report of the first annual Hawaii Asthma Research Consortium.
  Hawaii medical journal 2002 Chan DS, Callahan CW, Beckham S, Kishaba G, Yamamoto K, Malone FJ, Boychuk R, Tam E, Jourdan-Lesaux C, Underwood G, Vogt TM, Takafuji E
• Immunohistochemical localization of Pax2 and associated proteins in the developing kidney of mice with renal hypoplasia.
  The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 2001 Lozanoff S, Johnston J, Ma W, Jourdan-Le Saux C
• Central nervous system, uterus, heart, and leukocyte expression of the LOXL3 gene, encoding a novel lysyl oxidase-like protein.
  Genomics 2001 Jourdan-Le Saux C, Tomsche A, Ujfalusi A, Jia L, Csiszar K
• Lysyl oxidases: expression in the fetal membranes and placenta.
  Placenta 2001 Hein S, Yamamoto SY, Okazaki K, Jourdan-LeSaux C, Csiszar K, Bryant-Greenwood GD
• The mouse lysyl oxidase-like 2 gene (mLOXL2) maps to chromosome 14 and is highly expressed in skin, lung and thymus.
  Matrix biology : journal of the International Society for Matrix Biology 2000 Jourdan-Le Saux C, Le Saux O, Gleyzal C, Sommer P, Csiszar K
• Comparative functional study of the lysyl oxidase promoter in fibroblasts, Ras-transformed fibroblasts, myofibroblasts and smooth muscle cells.
  Cellular and molecular biology (Noisy-le-Grand, France) 1999 Reynaud C, Gleyzal C, Jourdan-Le Saux C, Sommer P
• The LOXL2 gene encodes a new lysyl oxidase-like protein and is expressed at high levels in reproductive tissues.
  The Journal of biological chemistry 1999 Jourdan-Le Saux C, Tronecker H, Bogic L, Bryant-Greenwood GD, Boyd CD, Csiszar K
• The human lysyl oxidase-related gene (LOXL2) maps between markers D8S280 and D8S278 on chromosome 8p21.2-p21.3.
  Genomics 1998 Jourdan-Le Saux C, Le Saux O, Donlon T, Boyd CD, Csiszar K
• Functional analysis of the lysyl oxidase promoter in myofibroblast-like clones of 3T6 fibroblast.
  Journal of cellular biochemistry 1997 Jourdan-Le Saux C, Gleyzal C, Raccurt M, Sommer P
• Lysyl oxidase cDNA of myofibroblast from mouse fibrotic liver.
  Biochemical and biophysical research communications 1994 Jourdan-Le Saux C, Gleyzal C, Garnier JM, Peraldi M, Sommer P, Grimaud JA
• Rapid mycobacterial plasmid analysis by electroduction between Mycobacterium spp. and Escherichia coli.
  Nucleic acids research 1992 Baulard A, Jourdan C, Mercenier A, Locht C