Wellington V. Cardoso, MD, PhD

Profile Headshot

Overview

Wellington V. Cardoso, MD, PhD, is Professor and the Director of the Columbia Center for Human Development at the Department of Medicine, Columbia University Medical Center.

Academic Appointments

  • Professor of Medicine (in Genetics and Development)

Administrative Titles

  • Director, Columbia Center for Human Development

Languages

  • Portuguese
  • Spanish

Gender

  • Male

Credentials & Experience

Education & Training

  • MD, 1981 Pathology, University of Brasilia, Faculty of Medicine (Brazil)
  • PhD, 1989 University of Sao Paulo (Brazil)
  • Fellowship: Boston University School Medicine
  • Fellowship: University of British Columbia (Canada)

Honors & Awards

International Invited Lectures

  • 2019, Invited Speaker: Epithelial-Mesenchymal Interactions in Lung Development & Fibrosis Conference: “Ontogeny & control of the airway stem cell pool in development & disease”, Nassau, Bahamas, Feb. 17-20.
  • 2018, Invited Speaker:   APSR 2018 Congress Meeting: “Airway progenitors from immaturity to postnatal disease”, Taipei, Taiwan, Nov. 28 – Dec 2.
  • 2017, Invited Speaker: Symvoli Conference: The Notch Meeting X – “Notch Control of Expansion and Differentiation of the Stem Cell Pool in Airways”; Athens, Greece; October 1-5.
  • 2017, Invited Speaker: Ustus-Liebig University, Geissen, Johann-Wolfgang-Goethe University, Frankfurt – Excellence Cluster CaridoPulmonary System (ECCPS) – New Perspectives in CardioPulmonary Research “Control of lineage specification and differentiation in airways”, Geissen, Germany; June 7-8.
  • 2016, Invited Speaker: University of Brasilia, “Prenatal Vitamin A deficiency in lung development and adult disease”, Sao Paulo, Brasilia, Brazil; November 20-26.
  • 2016, Invited Speaker: National Institute of Biological Sciences, Beijing – Lecture Series “Regulating the pool of epithelial progenitors in the developing and adult lung”, Beijing, China; Sept 1-3.
  • 2016, Invited Speaker: Universities of Giessen & Marburg Lung Center, 14th Annual Retreat, “Balancing the epithelial progenitor pool in airways”, Rauischholzhausen, Germany; Jul     20-22.
  • 2015, Invited Speaker: Latin American Society for Developmental Biology (LASDB), 8th Annual Meeting, Santos, Brazil; Oct 20-23.
  • 2015, Invited Speaker: German Society of Paediatrics (DGKJ) 2015 Conference, Munich, Germany; Sept 2-5.
  • 2014, Invited Speaker: Symposium - Bronchitis IX: ‘Lungs: On the Edge of Health & Ageing’, U. Medical Center, Groningen, Netherlands; June 23-25.
  • 2012, Invited Speaker: Symposium “Perspectives on the Lung”. University of Giessen, Marburg Lung Center: Giessen, Germany; Oct 22-24. 
  • 2012, Invited Lecture: Institute of Pulmonary Medicine; Hadassah University Hospital, Jerusalem, Israel; Mar 8. 
  • 2010, Invited Speaker & Visiting Professor: National Taiwan University Medical Center. “2010 Symposium on Developmental Biology and Stem Cells”:  Taipei, Taiwan; May 7-9. 
  • 2009, Invited Speaker: “Development & Aging:  Relevance to COPD”, Lund, Sweden; Apr 26.
  • 2007, Invited Lecture: “Retinoids in early lung morphogenesis”. University of Thessaloniki, Thessaloniki, Greece, Oct 3.
  • 2005, Invited Speaker and Session Co-Coordinator: “Model Organisms and Innovative Approaches in Developmental Biology”: Juquehy, Sao Paulo, Brazil; April 27 - May 4.
  • 2005, Invited Speaker: 2nd International Meeting of the Latin American Society of Developmental Biology. Sao Paulo, Brazil.  May 6.
  • 2005, Speaker: Conference on “Proteoglycans in signaling”, Stockholm (Runo), Sweden. Sept 7-11.
  • 2003, Invited Speaker and Co-Chair Session: Symposium: FGFs in organogenesis. “International Meeting on FGF in development and disease”: Oxford-Kobe Institute, Kobe, Japan; Oct 14. 
  • 2003, Invited Lecture:” Heparan sulfate-FGF interactions in lung development”. Nippon Medical School, Tokyo, Japan; Oct 7.
  • 2003,    Invited lecture: “FGFs and retinoic acid in lung morphogenesis”. Tokyo University of Pharmacy and Life Science, Tokyo, Japan; Oct 8. 
  • 2003, Invited lecture: Institute of Anatomy. University of Berne, Berne, Switzerland; Nov 7.
  • 2001, Invited speaker: "First Siena International Conference on Animal Models of Chronic Obstructive Pulmonary Disease", Siena, Italy; Oct 2.
  • 2001, XVI Annual Meeting of the Brazilian Federation of the Societies of Experimental Biology (FeSBE)" “Symposium: Molecular Control of Heart and Lung Organogenesis”: Caxambu, Brazil; Aug 30.
  • 2001, Invited Lecture: “Genetic regulation of lung development”. Department of Histology and Embryology, University of Sao Paulo: Sao Paulo, Brazil; Sept 1.
  • 2001, Invited Lecture: “Growth factors in organogenesis and pulmonary disease”. Instituto do Coracao, University of Sao Paulo School of Medicine: Sao Paulo, Brazil: Sept 2.

Research

Regulation of lung morphogenesis, progenitor/stem cell and lineage diffrentiation during development and disease.

I am a Professor of Medicine and Genetics & Development and director of the Columbia Center for Human Development (CCHD, Department of Medicine), a multi-disciplinary research hub for the investigation of organ development and regeneration and the developmental basis of human diseases. My research focuses on the regulation of lung development, regeneration-repair and the impact of prenatal fetal exposures on adult pulmonary diseases. My lab has a long-standing interest in studying the cellular and molecular mechanisms by which lung epithelial progenitors give rise to the various specialized cell types, including  multiciliated, secretory  and neuroendocrine cells. Furthermore, we have a major interest in studying the mechanisms that control the organization and behavior of the lung stem cell compartment and how their failure contribute to abnormal repair and chronic pulmonary diseases. Over the past two decades our studies have revealed key roles for Fgf, Notch, retinoids, Hippo-Yap and microRNAs in the development of the lung structure, innate immunity and the diversity and function of the stem cell compartment of airways. Our work has provided relevant mechanistic insights into a number of conditons, including, lung agenesis and hypoplasia, COPD, pulmonary fibrosis, asthma, and neuroendocrine hyperplasias.

Research Interests

  • Airway epithelial differentiation and pathogenesis of chronic airway diseases
  • Developmental basis of adult lung disease
  • Developmental signaling in lung formation and diseases
  • Formation and diversification of multiciliated cells in the respiratory system
  • Lung development and repair-regeneration
  • Ontogeny and regulation of the airway stem cell pool in the lung
  • Progenitor/Stem cell biology
  • SARS-COVID-2- host interactions in the lung

Grants

R35HL135834-05 (PI: Cardoso) 01/01/17 – 12/31/23
Mechanisms Controlling Expansion and Lineage Specification of Airway Progenitors in Development and Disease: This project is designed to study the mechanisms that control the organization and behavior of the stem cell compartment within the airways during development and to investigate the impact of disruption of these mechanisms in pulmonary disease pathogenesis.

R35 HL135834-04S1 (PI: Cardoso) 08/15/20 –07/31/21 (no cost extension)
NIH/NHLBI
Mechanisms Controlling Expansion and Lineage Specification of Airway Progenitors in Development and Disease: The devastating and rapid spread of the COVID-19 pandemic has revealed major gaps of knowledge on the mechanisms by which SARS-CoV-2 infects the airways and interferes with normal lung function. This R35 supplement addresses this problem and proposes to identify key gene regulators of this process as well as to test drugs to restrict infection and its deleterious effects.

R01HL145302-02 (PI: Suzuki, Co-I: Cardoso) 04/01/20 – 03/31/24        
NIH-NHLBI
Impact of Prenatal Vitamin A Deficiency on Cell Fate Alterations in Adult Airway Hyperresponsiveness: This proposal is based on a number of converging observations indicating that prenatal vitamin A status alters cell fate decisions in the fetus, resulting in cell subtype proportion changes in tissues postnatally that are associated with diseases later in life. We will test this novel potential mechanism for human disease with mouse models. We will map where in the mouse genome these transcriptional dysregulation events occur, and use this information to interpret the results of human genome-wide association studies, gaining mechanistic insights into the gene x environment interactions involved in common human diseases.

PR191133, (PI: Mori, Co-I Cardoso) 07/01/20 - 06/31/23
DoD Investigator-Initiated Research Award
A novel bioengineering approach for generation of functional lungs in swine. The major goals of the proposal are to elucidate the mechanism regulating the swine organogenesis program and establish the experimental basis of conditional blastocyst complementation in swine. 

1U01HL134760-05 (CoPI: Snoeck & Vunjak-Novakovic, CO-I: Cardoso) 09/01/16 – 05/31/23
Modeling and treating idiopathic pulmonary fibrosis using human induced pluripotent stem cells: This consortium project involves disease modeling of idiopathic pulmonary fibrosis using 3D models of directed differentiation of human pluripotent stem cells, as well novel bioengineering approaches to replace diseased lung tissues. As a further aim, we propose to generate the first large animal model of this disease.

Selected Publications

  • Cardoso WV. Maturation for Regeneration. Cell Stem Cell. 28, October 7, 2021 (in press).
  • Shui JE, Wang W, Liu H, Stepanova A, Liao G, Qian J, Ai X, Ten V, Lu J, Cardoso WV. Prematurity alters the progenitor cell program of the upper respiratory tract of neonates. Science Reports. 2021 May 24;11(1):10799. doi: 10.1038/s41598-021-90093-x. PMID: 34031475
  • Mou H, Yang Y, Riehs MA, Barrios J, Shivaraju M, Haber AL, Montoro DT, Gilmore K, Haas EA, Paunovic B, Rajagopal J, Vargas SO, Haynes RL, Fine A, Cardoso WV, Ai X. Airway basal stem cells generate distinct subpopulations of PNECs. Cell Reports. 2021 Apr 20;35(3):109011. doi: 10.1016/j.celrep.2021.109011. PMID: 33882306; PMCID: PMC8140387
  • Mori M, Furuhashi K, Danielsson JA, Hirata Y, Yamamoto M, Lin CS, Ohta M, Riccio P, Takahashi Y, Xu X, Emala CW, Lu C, Nakauchi H, Cardoso WV. Generation of functional lungs via conditional blastocyst complementation. Nature Medicine 2019 Nov 7. doi: 10.1038/s41591-019-0635-8..
  • van Soldt BJ, Qian J, Li J, Tang N, Lu J, Cardoso WV.  Yap and its subcellular localization have distinct compartment-specific roles in the developing lung. Development. 2019, 146(9). pii: dev175810. doi: 10.1242/dev.175810.PMID: 30944105.
  • Qiu H, Shi S, Yue J, Xin M, Nairn AV, Lin L, Liu X, Li G, Archer-Hartmann SA, Dela Rosa M, Galizzi M, Wang S, Zhang F, Azadi P, van Kuppevelt TH, Cardoso WV, Kimata K, Ai X, Moremen KW, Esko JD, Linhardt RJ, Wang L. A mutant-cell library for systematic analysis of heparan sulfate structure-function relationships. Nature Methods. 2018. 15(11):889-899. doi: 10.1038/s41592-018-0189-6.PMID: 30377379 
  • Yang Y, Riccio P, Schotsaert M, Mori M, Lu J, Lee DK, García-Sastre A, Xu J, Cardoso WV. Spatial-Temporal Lineage Restrictions of Embryonic p63+ Progenitors Establish Distinct Stem Cell Pools in Adult Airways. Developmental  Cell. 2018 Mar 26;44(6):752-761.e4.doi:10.1016/j.devcel.2018.03.001. PMID: 29587145.
  • Yang Y, Cardoso WV. Stem Cells Sheltered from Air-Raids Repair Airways. Cell Stem Cell. 2018 May 3;22(5):613-614. Doi: 10.1016/j.stem.2018.04.010. PMID:29727674.
  • Smith BM, Traboulsi H, Austin JHM, Manichaikul A, Hoffman EA, Bleecker ER, Cardoso WV, Cooper C, Couper DJ, Dashnaw SM, Guo J, Han MK, Hansel NN, Hughes EW, Jacobs DR Jr., Kanner RE, Kaufman JD, Kleerup E, Lin CL, Liu K, Lo Cascio CM, Martinez FJ, Nguyen JN, Prince MR, Rennard S, Rich SS, Simon L, Sun Y, Watson KE, Woodruff PG, Baglole CJ, Barr RG; MESA Lung and SPIROMICS investigators. Human airway branch variation and chronic obstructive pulmonary disease. Proc Natl Acad Sci USA. 2018 Jan 30; 115(5): E974-E981. Epub 2018 Jan 16. PMID: 29339516.
  • Mori M, Hazan R, Danielian PS, Mahoney JE, Li H, Lu J, Miller ES, Zhu X, Lees JA, Cardoso WV. Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis. Nature Communications. 2017 Jul 4;8:15857. Doi: 10.1038/ncoms 15857. PMID: 28675157.
  • Guha A, Deshpande A, Jain A, Sebastiani P, Cardoso WV. Uroplakin 3a+ Cells Are a Distinctive Population of Epithelial Progenitors that Contribute to Airway Maintenance and Post-injury Repair. Cell Reports. 2017 Apr 11;19(2):246-254. Doi: 10.1016/j.celrep.2017.03.051. PMID: 28402849.
  • Tsao PN, Matsuoka C, Wei SC, Sato A, Sato S, Hasegawa K, Chen HK, Ling TY, Mori M, Cardoso WV, Morimoto M. Epithelial Notch signaling regulates lung alveolar morphogenesis and airway epithelial integrity. Proc Natl Acad Sciences, USA. 2016 Jun 30. Pii: 201511236. PMID: 27364009.
  • Szymaniak AD, Mahoney JE, Cardoso WV, Varelas X. Crumbs3-Mediated Polarity Directs Airway Epithelial Cell Fate through the Hippo Pathway Effector Yap. Developmental Cell. 2015 Aug 10;34(3):283-96 doi: 10.1016/j.devcel.2015.06.020 Epub 2015 Jul 30. PMID: 26235047.
  • Mori M, Mahoney JE, Stupnikov MR, Paez-Cortez JR, Szymaniak AD, Varelas X, Herrick DB, Schwob J, Zhang H, Cardoso WV. Notch3-Jagged signaling controls the pool of undifferentiated airway progenitors. Development. 2015 Jan 15;142(2):258-67. doi: 10.1242/dev.116855. PMID: 25564622.
  • Mahoney JE, Mori M, Szymaniak A, Varelas X, Cardoso WV. The Hippo Pathway Effector Yap Controls Patterning and Differentiation of Airway Epithelial Progenitors. Developmental Cell. 2014 Jul 28;30(2):137-50. PMID: 25043473.
  • Chen F, Marquez H, Kim YK, Qian J, Shao F, Cruikshank K, Quadro L, Cardoso WV. Prenatal retinoid deficiency leads to airway hyperresponsiveness in adult mice. J. Clinical Investigation. 2014 Feb 124:801-11. PMID: 24401276.
  • Guha A, Vasconcelos M. Cai Y, Yoneda M, Hinds, Qian J, Li G, Dickel L, Johnson JE, Kimura S, Guo J, McMahon J, McMahon AP, Cardoso WV. The neuroepithelial body microenvironment is a niche for a distinct subset of Clara-like precursors in the developing airways.  Proc. Natl. Acad. Sciences. USA. 109:12592-12597, 2012. PMID: 22797898.
  • Tsao PN, Wei SC, Wu MF, Huang MT, Lin HY, Lee MC, Lin KMC, Wang IJ, Kaartinen V, Yang LT, Cardoso WV. Notch signaling prevents mucous metaplasia in mouse conducting airways during postnatal development. Development, 138:3533-43, 2011. PMID: 21791528.
  • Chen F, Cao Y, Qian J, Shao F, Niederreither K, Cardoso WV.  A retinoic acid-dependent network in the foregut controls formation of the mouse lung primordium. J. Clinical Investigation.120:2040-8, 2010. PMID: 20484817.
  • Tsao PN, Vasconcelos M, Izvolsky KI, Qian J, Lu J, Cardoso WV. Notch signaling controls the balance of ciliated and secretory cell fates in developing airways. Development. 2009 Jul; 136(13):2297-307. PMID: 19502490.
  • Cardoso WV, Lu J. Regulation of early lung development: questions, facts and controversies. Development 2006, 133, 1611-1624.