Charles Dela Cruz, MD, PhD
Associate Professor AdjunctCards
Additional Titles
Director, Center for Pulmonary Infection Research and Treatment (CPIRT)
Contact Info
Pulmonary, Critical Care & Sleep Medicine
PO Box 208057, 300 Cedar Street
New Haven, CT 06520-8057
United States
About
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
- Dela Cruz Lab
- Internal Medicine
- The Center for Precision Pulmonary Medicine (P2MED)
- Virology Laboratories
- 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
Overview
Medical Research Interests
ORCID
0000-0002-5258-1797- View Lab Website
Dela Cruz Lab
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Farida Ahangari, MD
Albert Ko, MD
Naftali Kaminski, MD
Akiko Iwasaki, PhD
Wonnie Ryu, MD, MPH
Jeff Gehlhausen, MD, PhD
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Infections
Publications
2024
Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries
Feng J, Kim J, Wang V, Chang D, Liu H, Bain W, Robinson K, Jie Z, Kotenko S, Dela Cruz C, Sharma L. Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries. Physiological Reports 2024, 12: e70104. PMID: 39455422, PMCID: PMC11511623, DOI: 10.14814/phy2.70104.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsIII interferon signalingType III interferon signalingLung injuryInterferon signalingBleomycin-induced weight lossInflammatory responseModel of lung injuryBacterial pathogen Pseudomonas aeruginosaAcute lung injuryPathogen Pseudomonas aeruginosaBacterial endotoxin LPSChemotherapeutic agent bleomycinType III interferonsAnti-inflammatory roleIncreased inflammatory signalingLate time pointsBleomycin modelKnockout miceEndotoxin LPSIII interferonsAntiviral cytokinesDay 3Inflammatory signalingEarly injuryImpaired recoveryPrior knowledge-guided vision-transformer-based unsupervised domain adaptation for intubation prediction in lung disease at one week
Yang J, Henao J, Dvornek N, He J, Bower D, Depotter A, Bajercius H, de Mortanges A, You C, Gange C, Ledda R, Silva M, Dela Cruz C, Hautz W, Bonel H, Reyes M, Staib L, Poellinger A, Duncan J. Prior knowledge-guided vision-transformer-based unsupervised domain adaptation for intubation prediction in lung disease at one week. Computerized Medical Imaging And Graphics 2024, 118: 102442. PMID: 39515190, DOI: 10.1016/j.compmedimag.2024.102442.Peer-Reviewed Original ResearchConceptsUnsupervised domain adaptationSpatial prior informationDomain adaptationLabeled dataData-driven approachUnsupervised domain adaptation modelMedical image analysis tasksImage analysis tasksTransformer-based modelsMedical image analysisPrior informationOutcome prediction tasksAdversarial trainingDistribution alignmentDomain shiftAttention headsClass tokenPoor generalizationAnalysis tasksTarget domainPrediction taskData distributionKnowledge-guidedLocal weightsMedical imagesSingle-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis.
Unterman A, Zhao A, Neumark N, Schupp J, Ahangari F, Cosme C, Sharma P, Flint J, Stein Y, Ryu C, Ishikawa G, Sumida T, Gomez J, Herazo-Maya J, Dela Cruz C, Herzog E, Kaminski N. Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2024, 210: 484-496. PMID: 38717443, PMCID: PMC11351796, DOI: 10.1164/rccm.202306-0979oc.Peer-Reviewed Original ResearchCitationsAltmetricConceptsStable idiopathic pulmonary fibrosisIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsProgressive idiopathic pulmonary fibrosisPeripheral immune systemT cellsPulmonary fibrosisCohort of IPF patientsAssociated with decreased survivalIdiopathic pulmonary fibrosis patientsPeripheral blood mononuclear cell samplesPeripheral blood cell populationsImmune systemFraction of TregsRegulatory T cellsBlood mononuclear cellsBlood cell populationsFlow cytometry analysisImmune aberrationsIPF patientsTregsMononuclear cellsSingle-cell RNA sequencingLung homogenatesMonocyte chemoattractantThe protein disulfide isomerase A3 and osteopontin axis promotes influenza‐induced lung remodelling
Kumar A, Mark Z, Carbajal M, DeLima D, Chamberlain N, Walzer J, Ruban M, Chandrasekaran R, Daphtary N, Aliyeva M, Poynter M, Janssen‐Heininger Y, Bates J, Alcorn J, Britto C, Dela Cruz C, Jegga A, Anathy V. The protein disulfide isomerase A3 and osteopontin axis promotes influenza‐induced lung remodelling. British Journal Of Pharmacology 2024, 181: 4610-4627. PMID: 39118388, DOI: 10.1111/bph.16511.Peer-Reviewed Original ResearchConceptsProtein disulfide isomerase A3Secreted phosphoprotein 1Lung fibrosisLung remodelingFibrotic remodelingViral infectionAssociated with pulmonary fibrosisInfluenza-infected patientsMacrophage colony-stimulating factorFibrotic lung remodelingSPP1 expressionRespiratory viral infectionsImproved oxygen saturationColony-stimulating factorLung fibrotic remodelingDebilitating clinical sequelaeIAV infectionFibrotic sequelaeClinical sequelaeTherapeutic optionsPulmonary fibrosisRetrospective analysisNeutralizing antibodiesCell culture modelHealthy controlsLongitudinal multicompartment characterization of host-microbiota interactions in patients with acute respiratory failure
Kitsios G, Sayed K, Fitch A, Yang H, Britton N, Shah F, Bain W, Evankovich J, Qin S, Wang X, Li K, Patel A, Zhang Y, Radder J, Dela Cruz C, Okin D, Huang C, Van Tyne D, Benos P, Methé B, Lai P, Morris A, McVerry B. Longitudinal multicompartment characterization of host-microbiota interactions in patients with acute respiratory failure. Nature Communications 2024, 15: 4708. PMID: 38830853, PMCID: PMC11148165, DOI: 10.1038/s41467-024-48819-8.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsAcute respiratory failureRespiratory failureCohort of COVID-19 patientsLung microbiotaMechanically ventilated patientsChronic obstructive pulmonary diseaseIllumina amplicon sequencingDNA sequencing technologiesHost-microbiota interactionsObstructive pulmonary diseaseCOVID-19 patientsAssociated with specific patternsAntibiotic exposureClinical factorsNanopore metagenomicsPredicting survivalPrecision medicine interventionsPrognostic biomarkerSequencing technologiesAmplicon sequencingPulmonary diseaseGut microbiotaCritical illnessMicrobial diversityHuman microbiomeClinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis
Xiao Z, Lin M, Song N, Wu X, Hou J, Wang L, Tian X, An C, Dela Cruz C, Sharma L, Chang D. Clinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis. IScience 2024, 27: 110110. PMID: 38974472, PMCID: PMC11225851, DOI: 10.1016/j.isci.2024.110110.Peer-Reviewed Original ResearchCitationsAltmetricConceptsViral sepsisCausative agent of sepsisAgent of sepsisCases of sepsisSusceptibility to secondary bacterial infectionsNon-sepsis patientsSecondary bacterial infectionPlatelet activation pathwaysMetabolomic characteristicsPlatelet dysfunctionSepsis phenotypesClinical featuresSystemic disease phenotypeSepsis patientsSepsisCOVID-19 pathologyBacterial infectionsProteomic signatureDisease phenotypeComplement proteinsBacterial pathogensProteomic dataActivation pathwayFunctional consequencesPathway proteinsLung Epithelium Releases Growth Differentiation Factor 15 in Response to Pathogen-mediated Injury
Shah F, Bahudhanapati H, Jiang M, Tabary M, van der Geest R, Tolman N, Kochin M, Xiong Z, Al-Yousif N, Sayed K, Benos P, Raffensperger K, Evankovich J, Neal M, Snyder M, Eickelberg O, Ray P, Dela Cruz C, Bon J, McVerry B, Straub A, Jurczak M, Suber T, Zhang Y, Chen K, Kitsios G, Lee J, Alder J, Bain W. Lung Epithelium Releases Growth Differentiation Factor 15 in Response to Pathogen-mediated Injury. American Journal Of Respiratory Cell And Molecular Biology 2024, 70: 379-391. PMID: 38301257, PMCID: PMC11109583, DOI: 10.1165/rcmb.2023-0429oc.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsLung injuryPlasma levelsLung epitheliumGDF15 levelsAssociated with plasma levelsAcute respiratory distress syndromeGrowth differentiation factor 15Acute respiratory failureRespiratory distress syndromeWild-type miceLung cytokine levelsHuman lung epitheliumAcute lung injuryDifferentiation factor 15Levels of GDF15Critically ill humansPrognostic of mortalitySARS-CoV-2 infectionCirculating GDF15 levelsRespiratory tract levelRespiratory failureDistress syndromeCytokine profileStress cytokinesCytokine levelsAnti-inflammatory Roles of Type I Interferon Signaling in the Lung
Feng J, Liu Y, Kim J, Ahangari F, Kaminski N, Bain W, Jie Z, Dela Cruz C, Sharma L. Anti-inflammatory Roles of Type I Interferon Signaling in the Lung. 2024, a6230-a6230. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6230.Peer-Reviewed Original ResearchInitial and Residual Cardiovascular Damage Remaining at Day 30 in Community-acquired Pneumonia
Méndez Ocaña R, González-Jiménez P, Mengot N, España P, Uranga A, Almirall J, Boixeda R, Alonso R, Piqueras M, Martínez-Dolz L, Dela Cruz C, Menéndez R. Initial and Residual Cardiovascular Damage Remaining at Day 30 in Community-acquired Pneumonia. 2024, a6241-a6241. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6241.Peer-Reviewed Original ResearchInhibition 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 Research
Academic Achievements & Community Involvement
activity Fishman’s Pulmonary Diseases and Disorders
Journal ServiceEditorDetails2019 - Presentactivity Frontiers in Immunology
Journal ServiceGuest EditorDetails2019 - Presentactivity Clinics in Chest Medicine, Viral and Atypical Pneumonia
Journal ServiceGuest EditorDetails2016 - Presentactivity Plos One
Journal ServiceAssociate EditorDetails2013 - Presentactivity Frontiers in Respiratory Pharmacology
Journal ServiceReviewerDetails2011 - Present
News & Links
News
- August 25, 2023
Medical Students Honored by American College of Physicians
- June 27, 2023
Drs. Silvia Vilarinho, Andrew Wang Named Physician Scientist Training Program Leadership
- May 22, 2023
Britto-Leon Receives Carol Basbaum Award
- April 24, 2023
Internal Medicine Residency: What Medical Students Should Know
Get In Touch
Contacts
Pulmonary, Critical Care & Sleep Medicine
PO Box 208057, 300 Cedar Street
New Haven, CT 06520-8057
United States
Locations
The Anlyan Center
Academic Office
300 Cedar Street, Ste S441
New Haven, CT 06519
Appointments
203.785.3627Fax
203.785.5952