Contact

Location: VA 512C

Department

Pulmonary Diseases

Claude J Le Saux , PhD

Adjunct Faculty

Personal Statement:

I am interested in the mechanisms by which aging and injury trigger cellular senescence in the lungs leading to the remodeling of the pulmonary tissue. My interest also centers around developing biomarkers that could be use in clinical trials of anti-fibrotic compounds.


Education

1989 Universite de Provence, Marseille, France BS MajorBiochemistry and Microbiology
1990 Universite de Provence, Marseille, France MS MajorCell and Molecular Biology
1991 Universite de Provence, Marseille, France MENG MajorMicrobiology and Biotechnology
1992 Universite de Provence, Marseille, France PhD MajorCell and Molecular Biology PhD Advisor Dr. Pascal Sommer

Research

Keywords of Interest:

Pulmonary Fibrosis, Senescence, Aging, Macrophage biology, Cardiac Remodeling

I am interested in the mechanisms by which aging and injury trigger cellular senescence in the lungs leading to the remodeling of the pulmonary tissue. I have built over the course of the last 20 years my expertise on remodeling/fibrosis and in the last 5 years on cellular senescence. This publication is one of the first ones to demonstrate not only the presence of senescent cells in aged lungs but their causal role of the age-associated remodeling features of the lungs

Calhoun C, Shivshankar P, Saker M, Sloane LB, Livi CB, Sharp ZD, Orihuela CJ, Adnot S, White ES, Richardson A, Jourdan Le Saux C. Senescent Cells Contribute to the Physiological Remodeling of Aged Lungs. J Gerontol A Biol Sci Med Sci. 2015 Jan 7;PubMed PMID: 25568097.

Senior Author

My initial work focused on the characterization of the transcriptional regulation of lysyl oxidase and collagen type I in the liver fibrosis. At that time only 2 members were characterized in the family of lysyl oxidase and lysyl oxidase-like family. By RNA screening and computer analysis, we identified additional unknown members. I spent my postdoctoral fellowship cloning and characterizing these additional members of the lysyl oxidase family in mouse and human (Lysyl oxidase-2, -3 and -4). Because of the identification and characterization of these additional proteins, a better understanding of the substrate specificity could be achieved and these proteins are now used as therapeutic targets in various fibrotic disorders

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. J Biol Chem. 1999 Apr 30;274(18):12939-44. PubMed PMID: 10212285.

First author

Awards & Accomplishments

1994 Pre-doctoral Fellowship Award Association pour la Recherche sur le Cancer
1995 Pre-doctoral Fellowship Award Association pour la Recherche sur le Cancer
1996 Pre-doctoral Fellowship Award Glaxo Pharmaceutical Products
1996 Award for best promising pre-doctoral fellow Association de la Technolopole de Gerland
2012 Young investigator award 17th colloquium on lung and airways fibrosis, Modena, Italy
2014 Carol Basbaum Award American Thoracic Society Respiratory Cell and Molecular Biology

Affiliations

2001 – present      American Thoracic Society
2009 – 2010          American Heart Association
2016 – present      Association for Research in Vision and Ophthalmology

Publications

Sanon VP, Sawaki D, Mjaatvedt CH, Jourdan Le Saux C. Myocardial tissue caveolae. Comprehensive Physiology. 2015; 5(2):871-86. PMID: 25880516

Pinkerton KE, Harbaugh M, Han MK, Jourdan Le Saux C, Van Winkle LS, Martin Ii WJ, Kosgei RJ, Carter EJ, Sitkin N, Smiley-Jewell SM, George M. Women and Lung Disease: Gender Differences and Global Health Disparities. American Journal of Respiratory and Critical Care Medicine. 2015; PMID: 25945507

Halaney DL, Zahedivash A, Phipps JE, Wang T, Dwelle J, Jourdan Saux C, Asmis R, Milner TE, Feldman MD. Differences in forward angular light scattering distributions between M1 and M2 macrophages. J Biomed Opt. 2015 PMID: 26538329.

Wan F, Letavernier E, Jourdan Le Saux C, 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 Am J Physiol Heart Circ Physiol. 2015. PMID: 26453333

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-β1 signaling attenuates lung and tumor fibrosis. J Clin Invest. 2017;127(10):3675-3688. doi: 10.1172/JCI94624. Epub 2017 Sep 5. PMID:/>     28872461

Jourdan Le Saux C, Chapman HA. Idiopathic Pulmonary Fibrosis: Cell Death and Inflammation Revisited. American Journal of Respiratory Cell and Molecular Biology. 2018; 59(2): 137 doi.org/10.1165/rcmb.2018-0083ED

Pereira BI, Devine OP, Vukmanovic-Stejic M, Chambers ES, Subramanian P, Patel N, Virasami A, Sebire NJ, Kinsler V, Valdovinos A, Jourdan Le Saux C, Passos JP, 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; 10:2387. 10.1038/s41467-019-10335-5

Ying Wei, M.D., Julia Jackson, B.S., Genevieve Montas, B.S., Darren Leong, B.S., Jeffrey A. Golden, M.D., Binh N. Trinh, M.D., Ph.D., Elena Foster, M.S., Justin M. Oldham, M.D., Angela L. Linderholm, Ph.D., Paul J. Wolters, M.D., Xiaopeng Li, M.D., Julia Klesney-Tait, M.D., Ph.D., Prerna Kotak, M.S., Martin Decaris, Ph.D., Scott Turner, Ph.D., Jin Woo Song, M.D., Ph.D., Claude Jourdan Le Saux, Ph.D., Kirk Jones, M.D., and Harold A. Chapman, M.D. Reversal of TGFb1-driven Profibrotic State in Pulmonary Fibrosis Patients. Submitted

Christopher D. Wiley, Alexis N. Brumwell, Sonnet S. Davis, Julia R. Jackson, Alexis Valdovinos, Cheresa Calhoun, Fatouma Alimirah, Carlos A. Castellanos, Richard Rui, Ying Wei, Harold A. Chapman, Arvind Ramanathan, Judith Campisi, and Claude Jourdan Le Saux. Secretion of Leukotrienes by Senescent Lung Fibroblasts promotes Pulmonary Fibrosis. J Clin Invest In-sight. In Revision

Fan H, Rosson G, Wolf M, Sadtler K, Elisseeff J, Pardoll D, Houssean F, Wu X, Narain E, Chung L, Lebid A, Mageau A, Jourdan Le Saux C, Tam A, Vanderzee I, Čiháková D, Maestas D, Zhang X, Andorko, J.Interleukin-17 and senescence regulate the foreign body. Science Translational Medicine. In Revision