Clemente Britto-Leon, MD
Assistant Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine)Cards
Appointments
Contact Info
Pulmonary, Critical Care & Sleep Medicine
PO Box 208057
New Haven, CT 06520-8057
United States
About
Titles
Assistant Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine)
Biography
Dr. Britto received his medical degree from the Luis Razetti School of Medicine at the Universidad Central de Venezuela in Caracas, Venezuela. He completed his Internal Medicine residency training at Albert Einstein Medical Center in Philadelphia.
Dr. Britto completed his fellowship training in Pulmonary & Critical Care Medicine at Yale, followed by a Fellowship in Adult Cystic Fibrosis sponsored by the Cystic Fibrosis Foundation. During his fellowship, Dr. Britto became involved in research focused on the pathogenesis of airway diseases in the laboratory of his mentor, Lauren Cohn, M.D.
Dr. Britto joined the faculty at Yale in 2013, where his clinical responsibilities include being a member of the Adult Cystic Fibrosis Program and attending in the Medical Intensive Care Unit. These activities complement his research program focused on understanding the role of the airway epithelium in the development of airway diseases such as asthma and cystic fibrosis.
Appointments
Pulmonary, Critical Care & Sleep Medicine
Assistant ProfessorPrimary
Other Departments & Organizations
Education & Training
- Fellowship
- Yale-New Haven Hospital (2013)
- Fellowship
- Yale-New Haven Hospital (2013)
- Residency
- Albert Einstein Medical Center (2008)
- Residency
- Albert Einstein Medical Center (2007)
- Internship
- Albert Einstein Medical Center (2005)
- MD
- Universidad Central de Venezuela (2002)
Research
Overview
Short Palate Lung and Nasal epithelium Clone 1 (SPLUNC1) is an abundant airway protein with host protective functions relevant to cystic fibrosis (CF), the most common fatal genetic disease in the United States. The antimicrobial defense, mucociliary clearance and ion tranport regulation properties of SPLUNC1 may be important in the development of CF lung disease, the main cause of mortality in these patients. Persistent pulmonary inflammation and neutrophilic infiltration are hallmarks of CF lung disease. Work in our laboratory suggests that SPLUNC1 may have a novel role in regulating neutrophilic airway inflammation, as SPLUNC1-deficient (splunc1-/-) mice have dramatically decreased airway neutrophils during acute inflammation induced by LPS compared to wild type (WT) littermates.
SPLUNC1 is decreased in the airways of patients during allergic inflammation and we have shown that SPLUNC1 is decreased by common respiratory pathogens in animal models of airway inflammation in vivo, and by interferon gamma in vitro. Interestingly, this suppression of SPLUNC1 appears to be impaired in lung explants of severe CF patients undergoing lung transplantation, where SPLUNC1 is increased despite chronic inflammation and infection. In preliminary work, we determined that the suppression of SPLUNC1 is also impaired in the bronchoalveolar lavage fluid (BALF) of unstimulated CFTR-deficient (cftr-/-) and F508del homozygous (F508del) mice, two animal models of CF indicating that these animal models may be useful to study the regulation of SPLUNC1 in CF.
Despite the apparent paradox between the pathological and protective role of SPLUNC1, little is known about the mechanisms that regulate its activity, the role that SPLUNC1 plays in neutrophilic inflammation and its sigificance in the development of CF lung disease. We believe that the suppression of SPLUNC1 is a protective mechanism to limit neutrophilic inflammation and subsequent airway injury and so, high SPLUNC1 in CF may be detrimental by promoting neutrophilic inflammation, a fundamental part of CF lung disease pathogenesis. The objective of our research program is to understand how SPLUNC1 influences neutrophilic airway inflammation and if the modulation of SPLUNC1 can limit airway inflammation in CF.
Regulation of SPLUNC1 expression by the airway epithelium: identification of mechanisms by which pathogens, PAMPs and cytokines modulate SPLUNC1 expression.
Mechanisms of neutrophilic inflammation control by SPLUNC1: characterization of the role of SPLUNC1 in neutrophil recruitment to the lungs during acute airway inflammation.
Role of SPLUNC1 in immune responses in CF: defining mechanisms by which SPLUNC1 is increased in CF and what effect this increase has in neutrophilic immune responses.
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Maor Sauler, MD
Naftali Kaminski, MD
Marie Egan, MD
Xiting Yan, PhD
Emanuela Bruscia, PhD
Jon Koff, MD
Publications
Featured Publications
SPLUNC1: a novel marker of cystic fibrosis exacerbations
Khanal S, Webster M, Niu N, Zielonka J, Nunez M, Chupp G, Slade MD, Cohn L, Sauler M, Gomez JL, Tarran R, Sharma L, Dela Cruz CS, Egan M, Laguna T, Britto CJ. SPLUNC1: a novel marker of cystic fibrosis exacerbations. European Respiratory Journal 2021, 58: 2000507. PMID: 33958427, PMCID: PMC8571118, DOI: 10.1183/13993003.00507-2020.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsAcute pulmonary exacerbationsSPLUNC1 levelsCystic fibrosisClinical outcomesCF participantsLong-term disease controlNasal epithelium clone 1Cystic fibrosis exacerbationsHigher AE riskLung function declineCytokines interleukin-1βTumor necrosis factorAE riskClinical worseningPulmonary exacerbationsStable patientsLung functionAirway clearanceFunction declineSputum collectionAcute inflammationInflammatory cytokinesMicrobiology findingsCF careClinical managementSingle-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis.
Schupp JC, Khanal S, Gomez JL, Sauler M, Adams TS, Chupp GL, Yan X, Poli S, Zhao Y, Montgomery RR, Rosas IO, Dela Cruz CS, Bruscia EM, Egan ME, Kaminski N, Britto CJ. Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2020, 202: 1419-1429. PMID: 32603604, PMCID: PMC7667912, DOI: 10.1164/rccm.202004-0991oc.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCF lung diseaseHealthy control subjectsImmune dysfunctionLung diseaseCystic fibrosisControl subjectsSputum cellsAbnormal chloride transportLung mononuclear phagocytesInnate immune dysfunctionDivergent clinical coursesImmune cell repertoireMonocyte-derived macrophagesCF monocytesAirway inflammationClinical courseProinflammatory featuresCell survival programInflammatory responseTissue injuryCell repertoireImmune functionTranscriptional profilesAlveolar macrophagesMononuclear phagocytes
2024
Cystic Fibrosis Bacteriophage Study at Yale (CYPHY)
Stanley G, Cochrane C, Chan B, Kortright K, Rahman B, Lee A, Vill A, Sun Y, Stewart J, Britto-Leon C, Harris Z, Talwalker J, Shabanova V, Turner P, Koff J. Cystic Fibrosis Bacteriophage Study at Yale (CYPHY). 2024, a6808-a6808. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6808.Peer-Reviewed Original ResearchCitationsInhibition of Protein Disulfide Isomerase A3 and Osteopontin Attenuates Influenza-induced Lung Fibrosis
Kumar A, Mark Z, Janssen-Heininger Y, Poynter M, Dela Cruz C, Britto-Leon C, Alcorn J, Jegga A, Anathy V. Inhibition of Protein Disulfide Isomerase A3 and Osteopontin Attenuates Influenza-induced Lung Fibrosis. 2024, a2819-a2819. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a2819.Peer-Reviewed Original ResearchUnderstanding Impact of CFTR Dysfunction on Airway Immune Cell Composition in Early Lung Disease Pathogenesis
Kockar Kizilirmak T, Yin H, Garrison A, Bruscia E, Egan M, Britto-Leon C. Understanding Impact of CFTR Dysfunction on Airway Immune Cell Composition in Early Lung Disease Pathogenesis. 2024, a6357-a6357. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6357.Peer-Reviewed Original ResearchCFTR Modulators Reprogram Sex-Specific Airway Neutrophil Signaling
Yin H, Kockar Kizilirmak T, Li N, Adams T, Sauler M, Gomez J, Britto-Leon C. CFTR Modulators Reprogram Sex-Specific Airway Neutrophil Signaling. 2024, a7454-a7454. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a7454.Peer-Reviewed Original Research
2023
41 CYstic Fibrosis bacterioPHage study at Yale (CYPHY)
Chan B, Kortright K, Stanley G, Cochrane C, Lee A, Vill A, Sun Y, Stewart J, Britto-Leon C, Harris Z, Talkwalkar J, Shabanova V, Turner P, Koff J. 41 CYstic Fibrosis bacterioPHage study at Yale (CYPHY). Journal Of Cystic Fibrosis 2023, 22: s22. DOI: 10.1016/s1569-1993(23)00976-1.Peer-Reviewed Original ResearchCitations
2022
Charting a New Path: A Single-Cell Atlas of Porcine Cystic Fibrosis Airways at Birth.
Britto CJ. Charting a New Path: A Single-Cell Atlas of Porcine Cystic Fibrosis Airways at Birth. American Journal Of Respiratory Cell And Molecular Biology 2022, 66: 585-586. PMID: 35294854, PMCID: PMC9163641, DOI: 10.1165/rcmb.2022-0065ED.Peer-Reviewed Original ResearchAtrial Esophageal Fistula: A Rare and Lethal Complication Following Catheter Ablation of Atrial Fibrillation
Harrington L, Stanley G, Khosla A, Britto-Leon C. Atrial Esophageal Fistula: A Rare and Lethal Complication Following Catheter Ablation of Atrial Fibrillation. 2022, a2853-a2853. DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2853.Peer-Reviewed Original ResearchCharacterization of the COPD alveolar niche using single-cell RNA sequencing
Sauler M, McDonough JE, Adams TS, Kothapalli N, Barnthaler T, Werder RB, Schupp JC, Nouws J, Robertson MJ, Coarfa C, Yang T, Chioccioli M, Omote N, Cosme C, Poli S, Ayaub EA, Chu SG, Jensen KH, Gomez JL, Britto CJ, Raredon MSB, Niklason LE, Wilson AA, Timshel PN, Kaminski N, Rosas IO. Characterization of the COPD alveolar niche using single-cell RNA sequencing. Nature Communications 2022, 13: 494. PMID: 35078977, PMCID: PMC8789871, DOI: 10.1038/s41467-022-28062-9.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsSingle-cell RNA sequencingRNA sequencingCell-specific mechanismsChronic obstructive pulmonary diseaseAdvanced chronic obstructive pulmonary diseaseTranscriptomic network analysisSingle-cell RNA sequencing profilesCellular stress toleranceAberrant cellular metabolismStress toleranceRNA sequencing profilesTranscriptional evidenceCellular metabolismAlveolar nicheSequencing profilesHuman alveolar epithelial cellsChemokine signalingAlveolar epithelial type II cellsObstructive pulmonary diseaseSitu hybridizationType II cellsEpithelial type II cellsSequencingCOPD pathobiologyHuman lung tissue samples
Clinical Trials
Current Trials
VX-121 Combination Therapy in Subjects With Cystic Fibrosis VX20-121-103
HIC ID2000030926RoleSub InvestigatorPrimary Completion Date07/31/2023Recruiting ParticipantsGenderBothAge12+ yearsScreening In Anticipation of Future Research
HIC ID2000021443RoleSub InvestigatorPrimary Completion Date12/31/2022Recruiting ParticipantsGenderBothAge2 years - 17 years
Clinical Care
Overview
Clinical Specialties
Fact Sheets
Asthma
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Board Certifications
Critical Care Medicine (Internal Medicine)
- Certification Organization
- AB of Internal Medicine
- Latest Certification Date
- 2021
- Original Certification Date
- 2011
Pulmonary Disease
- Certification Organization
- AB of Internal Medicine
- Latest Certification Date
- 2020
- Original Certification Date
- 2010
Yale Medicine News
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Media
- Immunofluorescence staining of untreated C57BL/6 tracheal epithelium shows that SPLUNC1 (Red) is highly expressed by airway epithelial cells. Cytokeratin (Green) has been used to stain airway epithelial cells. (All rights reserved, clemente.britto@yale.edu).
- Uniform Manifold Approximation and Projection (UMAP) of scRNAseq data from 20,095 sputum cells (CF n=9, HC n=5 subjects). Each dot represents a single cell. HC: Healthy controls; alvMΦ: alveolar MΦ, MoMΦ: Mo-derived MΦ; cDC: classical dendritic cell, pDC: plasmacytoid DC. Dashed circle: Mo/MΦ/DC excluding alvMΦ.
News
- May 22, 2023
Britto-Leon Receives Carol Basbaum Award
- May 20, 2023
Ferrante Wins Jo Rae Wright Award for Outstanding Science
- December 12, 2022Source: Yale News
Driver of cystic fibrosis lung inflammation yields target for treatment
- June 23, 2021
Despite the challenges of COVID-19, Yale-PCCSM section members continued their work on scientific papers
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Contacts
Pulmonary, Critical Care & Sleep Medicine
PO Box 208057
New Haven, CT 06520-8057
United States
Locations
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Are You a Patient? View this doctor's clinical profile on the Yale Medicine website for information about the services we offer and making an appointment.