Claude Chapman, PhD

Adjunct Professor

While dysfunctional alveolar epithelial cells type II (AECII) are thought to be central to the initiation of IPF, the mechanisms by which AECIIs provoke fibrosis are uncertain. Independent studies have shown that markers of cellular senescence (p53, p21, and p16INK4A) are upregulated in AECIIs in IPF lungs within the remodeled fibrotic areas. 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.

Education
PhD, 10/1996 - Cell and Molecular Biolog, Universite de Provence
MENG, 09/1991 - Microbiology and Biotechnology, Universite de Provence
MS, 06/1990 - Cell and Molecular Biology, Universite de Provence
BS, 06/1989 - Biochemistry and Microbiology, Universite de Provence
Honors and Awards
  • Carol Basbaum Award, American Thoracic Society Respiratory Cell and Molecular Biology, 2014
  • Young investigator award, 17th colloquium on lung and airways fibrosis, Modena, Italy, 2012
Publications

  1. Al Alam D, Ballard PL, Jourdan Le Saux C, Ingram JL, Mariani TJ, Moore NS, Weiss DJ, Yu M. Human Fetal Tissue Regulation. Impact on Pediatric and Adult Respiratory-related Research. Annals of the American Thoracic Society 2021. PMID: 33252996


  2. Wei Y, Dong W, Jackson J, Ho TC, Le Saux CJ, Brumwell A, Li X, Klesney-Tait J, Cohen ML, Wolters PJ, Chapman HA. Blocking LOXL2 and TGFβ1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis. Thorax 2021. PMID: 33472968


  3. Podolsky MJ, Yang CD, Lizama C, Datta R, Huang SK, Nishimura SL, Dallas SL, Wolters P, Jourdan Le Saux C, Atabai K. Age-dependent regulation of cell-mediated collagen turnover. JCI insight 2020. PMID: 32315288


  4. Chung L, Maestas DR, Lebid A, Mageau A, Rosson GD, Wu X, Wolf MT, Tam AJ, Vanderzee I, Wang X, Andorko JI, Zhang H, Narain R, Sadtler K, Fan H, Ciháková D, Le Saux CJ, Housseau F, Pardoll DM, Elisseeff JH. Interleukin 17 and senescent cells regulate the foreign body response to synthetic material implants in mice and humans. Science translational medicine 2020. PMID: 32295900


  5. Chapman HA, Wei Y, Montas G, Leong D, Golden JA, Trinh BN, Wolters PJ, Le Saux CJ, Jones KD, Hills NK, Foster E, Oldham JM, Linderholm AL, Kotak P, Decaris M, Turner S, Song JW. Reversal of TGFß1-Driven Profibrotic State in Patients with Pulmonary Fibrosis. The New England journal of medicine 2020. PMID: 32160670


  6. 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. Secretion of leukotrienes by senescent lung fibroblasts promotes pulmonary fibrosis. JCI insight 2019. PMID: 31687975


  7. 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. Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition. Nature communications 2019. PMID: 31160572


  8. Le Saux CJ, Chapman HA. Idiopathic Pulmonary Fibrosis: Cell Death and Inflammation Revisited. American journal of respiratory cell and molecular biology 2018. PMID: 29698615


  9. 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. Fibroblast-specific inhibition of TGF-ß1 signaling attenuates lung and tumor fibrosis. The Journal of clinical investigation 2017. PMID: 28872461


  10. Halaney DL, Zahedivash A, Phipps JE, Wang T, Dwelle J, Saux CJ, Asmis R, Milner TE, Feldman MD. Differences in forward angular light scattering distributions between M1 and M2 macrophages. Journal of biomedical optics 2015. PMID: 26538329


  11. 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. 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. PMID: 26453333


  12. 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. Women and Lung Disease. Sex Differences and Global Health Disparities. American journal of respiratory and critical care medicine 2015. PMID: 25945507


  13. Sanon VP, Sawaki D, Mjaatvedt CH, Jourdan-Le Saux C. Myocardial tissue caveolae. Comprehensive Physiology 2015. PMID: 25880516


  14. Sanders YY, Cui Z, Le Saux CJ, Horowitz JC, Rangarajan S, Kurundkar A, Antony VB, Thannickal VJ. SMAD-independent down-regulation of caveolin-1 by TGF-β: effects on proliferation and survival of myofibroblasts. PloS one 2015. PMID: 25658089


  15. Calhoun C, Shivshankar P, Saker M, Sloane LB, Livi CB, Sharp ZD, Orihuela CJ, Adnot S, White ES, Richardson A, Le Saux CJ. Senescent Cells Contribute to the Physiological Remodeling of Aged Lungs. The journals of gerontology. Series A, Biological sciences and medical sciences 2015. PMID: 25568097


  16. 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, Esteban A, LeSaux CJ, Tuomanen EI, Orihuela CJ. Streptococcus pneumoniae translocates into the myocardium and forms unique microlesions that disrupt cardiac function. PLoS pathogens 2014. PMID: 25232870


  17. Shivshankar P, Halade GV, Calhoun C, Escobar GP, Mehr AJ, Jimenez F, Martinez C, Bhatnagar H, Mjaatvedt CH, Lindsey ML, Le Saux CJ. Caveolin-1 deletion exacerbates cardiac interstitial fibrosis by promoting M2 macrophage activation in mice after myocardial infarction. Journal of molecular and cellular cardiology 2014. PMID: 25128086


  18. Medina JL, Coalson JJ, Brooks EG, Le Saux CJ, Winter VT, Chaparro A, Principe MF, Solis L, Kannan TR, Baseman JB, Dube PH. Mycoplasma pneumoniae CARDS toxin exacerbates ovalbumin-induced asthma-like inflammation in BALB/c mice. PloS one 2014. PMID: 25058417


  19. Royce SG, Le Saux CJ. Role of caveolin-1 in asthma and chronic inflammatory respiratory diseases. Expert review of respiratory medicine 2014. PMID: 24742020


  20. Hung JY, Horn D, Woodruff K, Prihoda T, LeSaux C, Peters J, Tio F, Abboud-Werner SL. Colony-stimulating factor 1 potentiates lung cancer bone metastasis. Laboratory investigation; a journal of technical methods and pathology 2014. PMID: 24468794


  21. Gabehart KE, Royce SG, Maselli DJ, Miyasato SK, Davis EC, Tang ML, Jourdan Le Saux C. Airway hyperresponsiveness is associated with airway remodeling but not inflammation in aging Cav1-/- mice. Respiratory research 2013. PMID: 24138138


  22. 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. A novel telomerase activator suppresses lung damage in a murine model of idiopathic pulmonary fibrosis. PloS one 2013. PMID: 23516479


  23. Ramirez TA, Jourdan-Le Saux C, Joy A, Zhang J, Dai Q, Mifflin S, Lindsey ML. Chronic and intermittent hypoxia differentially regulate left ventricular inflammatory and extracellular matrix responses. Hypertension research : official journal of the Japanese Society of Hypertension 2012. PMID: 22495609


  24. Shivshankar P, Brampton C, Miyasato S, Kasper M, Thannickal VJ, Le Saux CJ. Caveolin-1 deficiency protects from pulmonary fibrosis by modulating epithelial cell senescence in mice. American journal of respiratory cell and molecular biology 2012. PMID: 22362388


  25. Shivshankar P, Boyd AR, Le Saux CJ, Yeh IT, Orihuela CJ. Cellular senescence increases expression of bacterial ligands in the lungs and is positively correlated with increased susceptibility to pneumococcal pneumonia. Aging cell 2011. PMID: 21615674


  26. Miyasato SK, Loeffler J, Shohet R, Zhang J, Lindsey M, Le Saux CJ. Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling. Matrix biology : journal of the International Society for Matrix Biology 2011. PMID: 21641995


  27. Jourdan-Lesaux C, Zhang J, Lindsey ML. Extracellular matrix roles during cardiac repair. Life sciences 2010. PMID: 20670633


  28. Le Saux O, Teeters K, Miyasato S, Choi J, Nakamatsu G, Richardson JA, Starcher B, Davis EC, Tam EK, Jourdan-Le Saux C. The role of caveolin-1 in pulmonary matrix remodeling and mechanical properties. American journal of physiology. Lung cellular and molecular physiology 2008. PMID: 18849439


  29. Le Saux CJ, Teeters K, Miyasato SK, Hoffmann PR, Bollt O, Douet V, Shohet RV, Broide DH, Tam EK. 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. PMID: 18056268


  30. Hoffmann PR, Jourdan-Le Saux C, Hoffmann FW, Chang PS, Bollt O, He Q, Tam EK, Berry MJ. A role for dietary selenium and selenoproteins in allergic airway inflammation. Journal of immunology (Baltimore, Md. : 1950) 2007. PMID: 17709542


  31. Hoffmann PR, Gurary A, Hoffmann FW, Jourdan-Le Saux C, Teeters K, Hashimoto AC, Tam EK, Berry MJ. A new approach for analyzing cellular infiltration during allergic airway inflammation. Journal of immunological methods 2007. PMID: 17825315


  32. Harrigan RC, Easa D, LeSaux C, Millar L, Kagihara LE, Shomaker TS, Greer MH, Beck JD, Offenbacher S. Oral health disparities and periodontal disease in Asian and Pacific Island populations. Ethnicity & disease 2005. PMID: 16315381


  33. Hayashi K, Cao T, Passmore H, Jourdan-Le Saux C, Fogelgren B, Khan S, Hornstra I, Kim Y, Hayashi M, Csiszar K. 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. PMID: 15482472


  34. Tam EK, Jourdan-LeSaux C, Stauder S, Bollt O, Reber B, Yamamoto F, Haymer D. 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. PMID: 14984008


  35. Jourdan-Le Saux C, Bollt O, Orozco C, Concepcion J, Yamaga K, Yamamoto F, Haymer D, Tam EK. 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. PMID: 14682393


  36. 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. Report of the first annual Hawaii Asthma Research Consortium. Hawaii medical journal 2002. PMID: 12422384


  37. Lozanoff S, Johnston J, Ma W, Jourdan-Le Saux C. 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. PMID: 11511678


  38. Jourdan-Le Saux C, Tomsche A, Ujfalusi A, Jia L, Csiszar K. Central nervous system, uterus, heart, and leukocyte expression of the LOXL3 gene, encoding a novel lysyl oxidase-like protein. Genomics 2001. PMID: 11386757


  39. Hein S, Yamamoto SY, Okazaki K, Jourdan-LeSaux C, Csiszar K, Bryant-Greenwood GD. Lysyl oxidases: expression in the fetal membranes and placenta. Placenta 2001. PMID: 11162352


  40. Jourdan-Le Saux C, Le Saux O, Gleyzal C, Sommer P, Csiszar K. 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. PMID: 10842102


  41. Reynaud C, Gleyzal C, Jourdan-Le Saux C, Sommer P. 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. PMID: 10643973


  42. Jourdan-Le Saux C, Tronecker H, Bogic L, Bryant-Greenwood GD, Boyd CD, Csiszar K. 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. PMID: 10212285


  43. Jourdan-Le Saux C, Le Saux O, Donlon T, 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. PMID: 9722957


  44. Jourdan-Le Saux C, Gleyzal C, Raccurt M, Sommer P. Functional analysis of the lysyl oxidase promoter in myofibroblast-like clones of 3T6 fibroblast. Journal of cellular biochemistry 1997. PMID: 9027591


  45. Jourdan-Le Saux C, Gleyzal C, Garnier JM, Peraldi M, Sommer P, Grimaud JA. Lysyl oxidase cDNA of myofibroblast from mouse fibrotic liver. Biochemical and biophysical research communications 1994. PMID: 7510957


  46. Baulard A, Jourdan C, Mercenier A, Locht C. Rapid mycobacterial plasmid analysis by electroduction between Mycobacterium spp. and Escherichia coli. Nucleic acids research 1992. PMID: 1508702