Adjunct faculty typically have an academic or research appointment at another institution and contribute or collaborate with one or more School of Medicine faculty members or programs.
Adjunct rank detailsCharles Dela Cruz, MD, PhD
Associate Professor AdjunctAbout
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Titles
Associate Professor Adjunct
Director, Center for Pulmonary Infection Research and Treatment (CPIRT)
Biography
Dr. Dela Cruz completed his research training through an MD/PhD program in the area of immunology and virology from University of Toronto and Yale. Clinically, he is trained in internal medicine, and specializes in pulmonary and critical care medicine and is currently an Associate Professor at Yale University in the same department. He is also the founding director for the Center for Pulmonary Infection Research and Treatment (CPIRT). www.cpirt.yale.edu. His laboratory is interested in studying the role of respiratory infection in the pathogenesis of acute and chronic lung diseases. Specifically, his work focuses on how lung infection contribute to inflammation, injury and tissue repair in the lung. This has allowed the lab to carefully study the molecular and cellular responses of several novel mediators in the lung.
His laboratory focuses on two main research programs. (1) Studying novel immune regulators in the lung during respiratory infections. (2) Studying the effects of cigarette smoke (CS) exposure in the pathogenesis of airway and lung diseases such as chronic obstructive pulmonary disease (COPD) using preclinical genetic mouse models and human biosamples. The goal of the lab is also to be able to confirm and translate the findings using biospecimens from the established and establishing cohort of human patients with various lung diseases.
COPD is a composite entity that includes chronic bronchitis and emphysema, is a leading cause of death in the world, and is a disease that is in need of new treatments. One of the goal of our laboratory is to investigate the interaction between CS and respiratory virus infection in the pathogenesis of COPD and identify novel therapeutic targets for this respiratory disease. It has been long thought that the frequent respiratory infections in COPD patients are due to their depressed immune function. Our studies have revealed that CS-exposed hosts have an over-exaggerated immune reaction to viral infections. Frequent acute COPD exacerbations correlate with increased rate of disease progression and more loss of lung function in COPD especially if it is due to viral infections. Our studies have shown that CS exposure has an impressive ability to regulate the innate immunity in the lung after influenza virus and respiratory syncytial virus (RSV) infection. CS enhances the inflammation, alveolar destruction and airway fibrosis caused by influenza virus and RSV. These effects are mediated by type I interferon and RIG-like helicase antiviral innate immune pathway. CS exposure also results in the induction of interleukin-15 in the setting of these respiratory infections. We hypothesize that these novel mechanistic pathways may explain the heightened inflammatory response and worsening lung functions in COPD patients with multiple virally-induced exacerbations, and the chronic lung inflammation seen in stable COPD patients. We have also translated our findings by studying these immune mediators in patients infected with various respiratory viruses and have thus far collected >300 human biosamples.
YCCI Scholar 2011
Departments & Organizations
- ABIM Physician-Scientist Research Pathway
- Center for Infection and Immunity
- CPIRT - Center for Pulmonary Injury, Inflammation, Repair and Therapeutics
- Internal Medicine
- Winchester Center for Lung Disease
- Yale Stem Cell Center
- Yale Ventures
Education & Training
- Fellow
- Yale University School of Medicine (2009)
- Resident
- Yale University School of Medicine (2005)
- MD
- Yale University School of Medicine (2003)
- PhD
- University of Toronto (2000)
- BS
- University of Toronto (1994)
Research
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Overview
Medical Research Interests
ORCID
0000-0002-5258-1797
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Lokesh Kumar Sharma, PhD
Akiko Iwasaki, PhD
Jack Elias, MD
Shelli Farhadian, MD, PhD
Albert Icksang Ko, MD
Ashley Losier, MD
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Infections
Publications
2026
Inhalation exposure to surrogate military burn pit emissions impairs systemic microvascular function: linking pulmonary insult and diverse peripheral responses
Nguyen V, Ranpara A, Goldsmith W, Batchelor T, Hoyer J, Leonard H, Razazan A, Lewis S, Krafcheck J, Burns R, Nelson R, Sharma P, Walton J, Beru N, Bain W, Cruz C, Wilson M, Kelley E, Hussain S, Nurkiewicz T. Inhalation exposure to surrogate military burn pit emissions impairs systemic microvascular function: linking pulmonary insult and diverse peripheral responses. Particle And Fibre Toxicology 2026 PMID: 42286691, DOI: 10.1186/s12989-026-00691-8.Peer-Reviewed Original ResearchConceptsPulmonary insultMicrovascular functionEndothelium-dependent arteriolar dilationMarkers of lung inflammationSystemic microvascular functionChronic multisymptom illnessSprague Dawley ratsCombustible mixtureInhalation exposureVascular nitric oxideTranscriptional markersWhole-body inhalation exposure chambersVasoconstrictor sensitivityPulmonary inflammationBronchoalveolar lavageLung inflammationArteriolar dilationMass median aerodynamic diameterSystemic syndromeDawley ratsEndothelial dysfunctionCellular infiltrationImmune responsePeripheral responsesIntravital microscopyPneumonia Reimagined: Host, Microbe, and the Shifting Landscape of Disease
Pickens C, Jones B, Dela Cruz C. Pneumonia Reimagined: Host, Microbe, and the Shifting Landscape of Disease. Clinics In Chest Medicine 2026, 47: xiii-xiv. PMID: 42203430, DOI: 10.1016/j.ccm.2026.03.001.Peer-Reviewed Original ResearchSoluble Thrombomodulin Links Viremia and Mortality During COVID-19: Results From the ACTIV-4a Trial.
Zuchelkowski B, Inman K, Nouraie S, Beru N, Naqvi A, Qin S, Yeh C, Zhang Y, Shah F, Sharma L, Dela Cruz C, Zhang L, McVerry B, Morris A, Neal M, Seheult J, Kitsios G, Mellors J, Lawrence D, Kim P, Jacobs J, Bain W. Soluble Thrombomodulin Links Viremia and Mortality During COVID-19: Results From the ACTIV-4a Trial. Journal Of The American Heart Association 2026, 15: e047693. PMID: 42089155, DOI: 10.1161/jaha.125.047693.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsViral RNA levelsSoluble thrombomodulinAssociated with deathCardiovascular complicationsRNA levelsRandomized trials of antithrombotic therapyRandomized trialsSARS-CoV-2Trials of antithrombotic therapyRespiratory viral infectionsViral RNAAntithrombotic therapyClinical outcomesRespiratory virusesCox regressionViral disseminationEndotheliopathyViral infectionFine-GraySARS-CoV-2 RNA levelsMortality rateThrombomodulinSARS-CoV-2 RNAViremiaN antigenCharacterization and Three-Year Survival of Clinical Subtypes and Host Response Phenotypes of Acute Respiratory Failure Requiring Mechanical Ventilation
Kitsios G, Bain W, Evankovich J, Prendergast N, Hensley M, Suber T, Inman K, Schaefer C, Saul M, Chen X, Haque M, Lee J, Rizzo A, Qin S, Zhang Y, Morris A, Dela Cruz C, Nouraie S, McVerry B, Shah F. Characterization and Three-Year Survival of Clinical Subtypes and Host Response Phenotypes of Acute Respiratory Failure Requiring Mechanical Ventilation. CHEST Critical Care 2026, 100274. DOI: 10.1016/j.chstcc.2026.100274.Peer-Reviewed Original ResearchConceptsAcute respiratory distress syndromeAcute respiratory failureThree-year survivalLong-term outcomesRespiratory failureAcute exacerbationMechanical ventilationAcute-on-chronic hypercapnic respiratory failureAirway controlClinical subtypesAcute exacerbation of interstitial lung diseaseExacerbation of interstitial lung diseaseHost response phenotypesBiological subphenotypesCharacterization of clinical featuresHypercapnic respiratory failureInvasive mechanical ventilationRespiratory distress syndromeInterstitial lung diseaseLong-term prognosisCongestive heart failureMechanically Ventilated PatientsPlasma inflammatory biomarkersProspective cohort studyLong-term survivalA104-08 Persistent Endothelial Glycocalyx Degradation Is Associated With Mortality in Chronic Critical Illness
Rizzo A, Francisco J, Li X, Zhang Y, Kitsios G, Dela Cruz C, Mcverry B, Nouraie M, Zemke A. A104-08 Persistent Endothelial Glycocalyx Degradation Is Associated With Mortality in Chronic Critical Illness. American Journal Of Respiratory And Critical Care Medicine 2026, 212: aamag162.4810. DOI: 10.1093/ajrccm/aamag162.4810.Peer-Reviewed Original ResearchConceptsChronic critical illnessPlasma syndecan-1Long-term acute care hospitalEndothelial glycocalyx degradationObservational cohort studyAcute critical illnessCritical illnessSyndecan-1Hazard ratioVentilator weaningIL-6IL-8Glycocalyx degradationPlasma syndecan-1 concentrationInflammatory vascular injuryObservational cohort study of individualsSyndecan-1 levelsSyndecan-1 concentrationsEndothelial glycocalyxInflammatory cytokines IL-6Chronically critically ill patientsCritical illness syndromeCritically ill patientsAssociated with mortalityCytokines IL-6D93-06 Systematic Characterization and Three-year Survival of Acute Respiratory Failure Clinical Subtypes and Biologic Subphenotypes
Kitsios G, Bain W, Evankovich J, Prendergast N, Hensley M, Suber T, Inman K, Schaefer C, Nina L, Melissa S, Chen X, Menaal H, Lee J, Rizzo A, Qin S, Zhang Y, Morris A, Dela Cruz C, Nouraie M, Mcverry B, Shah F. D93-06 Systematic Characterization and Three-year Survival of Acute Respiratory Failure Clinical Subtypes and Biologic Subphenotypes. American Journal Of Respiratory And Critical Care Medicine 2026, 212: aamag162.246. DOI: 10.1093/ajrccm/aamag162.246.Peer-Reviewed Original ResearchConceptsAcute exacerbation of interstitial lung diseaseCongestive heart failureThree-year survivalAirway controlRespiratory failureInflammatory subphenotypesAcute exacerbationMechanical ventilationAcute-on-chronic hypercapnic respiratory failureExacerbation of interstitial lung diseaseRadiographic severityBiological subphenotypesHost response biomarkersHypercapnic respiratory failureAcute respiratory failureCongestive heart failure patientsNinety-day mortalityInvasive mechanical ventilationInterstitial lung diseasePlasma inflammatory biomarkersMechanically Ventilated PatientsLong-term survivalAt-riskHypercapnic failureEjection fractionD101-09 Genetic Variation in the Alternative Pathway of Complement and Individual Susceptibility to Pneumonia in the Veterans Affairs Million Veteran Program
Inman K, Chernus J, Alder J, Sharma L, Kulkarni H, Strollo P, Dela Cruz C, Feingold E, Bain W. D101-09 Genetic Variation in the Alternative Pathway of Complement and Individual Susceptibility to Pneumonia in the Veterans Affairs Million Veteran Program. American Journal Of Respiratory And Critical Care Medicine 2026, 212: aamag162.4550. DOI: 10.1093/ajrccm/aamag162.4550.Peer-Reviewed Original ResearchConceptsExpression quantitative trait lociSingle nucleotide polymorphismsIntergenic single nucleotide polymorphismLinkage disequilibriumGenetic variationExpression quantitative trait loci dataTrans-ancestral meta-analysisVeterans AffairsLead single nucleotide polymorphismsSignificant SNPsUnique single nucleotide polymorphismsIdentification of genetic variantsVeterans Affairs Million Veteran ProgramAlternative pathwayQuantitative trait lociAlternative pathway of complementPathway of complementPathway activationFungal pneumoniaMillion Veteran ProgramAssociated with variantsGenome-wideLead variantsAlternative pathway proteinsNear genesC107-03 Micro-Bronchoscopy Enables Serial Bronchoalveolar Lavage Sampling for Longitudinal Assessment of Inflammatory Injury in Mice
Kohn A, Francisco J, Guo L, Packwood M, Sharma L, Cruz C, Eickelberg O, Bueno M, Rizzo A. C107-03 Micro-Bronchoscopy Enables Serial Bronchoalveolar Lavage Sampling for Longitudinal Assessment of Inflammatory Injury in Mice. American Journal Of Respiratory And Critical Care Medicine 2026, 212: aamag162.224. DOI: 10.1093/ajrccm/aamag162.224.Peer-Reviewed Original ResearchConceptsBronchoalveolar lavage fluidLung injuryMice treated with bleomycinIntrapulmonary airwaysAnalysis of bronchoalveolar lavage fluidPost-treatment follow-up periodModel of acute lung injuryModel of lung injuryMurine model of lung injuryBronchoalveolar lavage fluid samplesInflammatory lung injuryFollow-up periodBronchoalveolar lavage samplesAcute lung injuryInflammatory lung diseasesBAL fluid recoveryLung injury modelLongitudinal assessmentInstilled volumeUninjured lungsBAL samplesFemale miceLavage fluidLung diseaseInflammatory environmentC96-02 Proteasome Dysfunction Modulates Host Response to Influenza Infection
Verdone J, Chandler M, Villandre J, Sharma L, Qin S, Dela Cruz C, Evankovich J. C96-02 Proteasome Dysfunction Modulates Host Response to Influenza Infection. American Journal Of Respiratory And Critical Care Medicine 2026, 212: aamag162.4517. DOI: 10.1093/ajrccm/aamag162.4517.Peer-Reviewed Original ResearchConceptsInfluenza A Virus InfectionInfluenza A virusPrecision-cut lung slicesHuman precision-cut lung slicesInfluenza infectionHost response to IAV infectionHost response to influenza infectionResponse to influenza infectionInfluenza A virus replicationResponse to IAV infectionInfluenza A virus nucleoproteinInfluenza A virus NPIndependent risk factorInfluenza matrix proteinTranscription of proinflammatory genesExpression of proinflammatory markersProteasome dysfunctionHost response to infectionMatrix proteinsInfection in vitroProteasome activityHost-directed therapeutic targetAntiviral gene expressionResponse to infectionIAV infectionC67-06 Aging and Sex Differentially Shape Myeloid Responses and Viral Clearance During Influenza Infection
Kim J, Qiu A, Bain W, Abu Hussein N, Agaronyan K, Suber T, Rizzo A, Evankovich J, Dela Cruz C, Zhao A, Yuan Y, Manning E, Chen L, Sharma L. C67-06 Aging and Sex Differentially Shape Myeloid Responses and Viral Clearance During Influenza Infection. American Journal Of Respiratory And Critical Care Medicine 2026, 212: aamag162.4460. DOI: 10.1093/ajrccm/aamag162.4460.Peer-Reviewed Original ResearchConceptsInfluenza infectionViral clearanceSevere influenzaInnate immune response to influenzaRisk of severe influenzaSusceptibility to severe influenzaImmune response to influenzaDefective viral clearanceResponse to influenzaViral transcriptionInflammatory gene signatureFemale C57BL/6 micePersistent pulmonary inflammationWeight lossSex-dependent alterationsAged neutrophilsBody weight lossNS1 protein expressionHigh-risk populationProinflammatory gene expressionCell activity patternsHuman challenge studiesViral RNA quantificationMyeloid populationsPulmonary inflammation
Academic Achievements & Community Involvement
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Activities
activity NHLBI, LCMI Study Section
2020 - PresentPeer Review Groups and Grant Study SectionsChairactivity American Thoracic Society, Scientific Advisory Committee
2015 - PresentPeer Review Groups and Grant Study SectionsAdvisoractivity American Lung Association, Research Fellowship Grants
2015 - PresentPeer Review Groups and Grant Study SectionsRevieweractivity Fishman’s Pulmonary Diseases and Disorders
2019 - PresentJournal ServiceEditoractivity Frontiers in Immunology
2019 - PresentJournal ServiceGuest Editor
Honors
honor Elected Chair, Gordon Conference, Biology of Acute Lung Infections; Vice-chair (2022)
02/08/2021National AwardDetailsUnited Stateshonor Chair, NHLBI, Lung Cellular and Molecular Immunity (LCMI) Study Section
02/19/2020National AwardDetailsUnited Stateshonor co-Editors, Fishman’s Pulmonary Diseases and Disorders, 6e, Michael A. Grippi, Robert M. Kotloff, Allan I. Pack, Charles S. Dela Cruz, Camille Kotton, Danielle Antin-Ozerkis
02/12/2019National AwardDetailsUnited Stateshonor American Thoracic Society (ATS) Fellow
08/06/2018National AwardDetailsUnited Stateshonor Pulmonary Infection and Tuberculosis (PI-TB) Mid-Level Career Award
08/01/2018National AwardAmerican Thoracic Society (ATS)DetailsUnited States
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