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
Appointments
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 Subject Headings (MeSH)
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
Jennifer Possick, MD
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Infections
Publications
2024
Single-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 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 controlsClinical 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 ResearchAltmetricConceptsViral 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 proteinsInitial 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 ResearchChitotriosidase Regulates Host Response to Influenza Lung Infection
Kim J, Amick A, Sharma L, Dela Cruz C. Chitotriosidase Regulates Host Response to Influenza Lung Infection. 2024, a4183-a4183. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a4183.Peer-Reviewed Original ResearchAnti-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 ResearchIntranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Mao T, Kim J, Peña-Hernández M, Valle G, Moriyama M, Luyten S, Ott I, Gomez-Calvo M, Gehlhausen J, Baker E, Israelow B, Slade M, Sharma L, Liu W, Ryu C, Korde A, Lee C, Monteiro V, Lucas C, Dong H, Yang Y, Initiative Y, Gopinath S, Wilen C, Palm N, Dela Cruz C, Iwasaki A, Vogels C, Hahn A, Chen N, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Grubaugh N. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319566121. PMID: 38648490, PMCID: PMC11067057, DOI: 10.1073/pnas.2319566121.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsInterferon-stimulated genesRespiratory infectionsStrains of influenza A virusTreatment of respiratory viral infectionsRespiratory virus infectionsInfluenza A virusMouse model of COVID-19Respiratory viral infectionsNeomycin treatmentExpression of interferon-stimulated genesUpper respiratory infectionInterferon-stimulated gene expressionLower respiratory infectionsBroad spectrum of diseasesAdministration of neomycinRespiratory viral diseasesDisease to patientsUpper respiratory tractIntranasal deliveryCongenic miceIntranasal applicationNasal mucosaSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2A virusHost-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology
Phan H, Tsitsiklis A, Maguire C, Haddad E, Becker P, Kim-Schulze S, Lee B, Chen J, Hoch A, Pickering H, van Zalm P, Altman M, Augustine A, Calfee C, Bosinger S, Cairns C, Eckalbar W, Guan L, Jayavelu N, Kleinstein S, Krammer F, Maecker H, Ozonoff A, Peters B, Rouphael N, Montgomery R, Reed E, Schaenman J, Steen H, Levy O, Diray-Arce J, Langelier C, Erle D, Hendrickson C, Kangelaris K, Nguyen V, Lee D, Chak S, Ghale R, Gonzalez A, Jauregui A, Leroux C, Altamirano L, Rashid A, Willmore A, Woodruff P, Krummel M, Carrillo S, Ward A, Patel R, Wilson M, Dandekar R, Alvarenga B, Rajan J, Schroeder A, Fragiadakis G, Mick E, Guerrero Y, Love C, Maliskova L, Adkisson M, Ehrlich L, Melamed E, Rousseau J, Hurley K, Geltman J, Siles N, Rogers J, Kutzler M, Bernui M, Cusimano G, Connors J, Woloszczuk K, Joyner D, Edwards C, Lin E, Melnyk N, Powell D, Kim J, Goonewardene I, Simmons B, Smith C, Martens M, Croen B, Semenza N, Bell M, Furukawa S, McLin R, Tegos G, Rogowski B, Mege N, Ulring K, Holland S, Rosen L, Lee S, Vaysman T, Fernandez-Sesma A, Simon V, Van Bakel H, Gonzalez-Reiche A, Qi J, Carreño J, Singh G, Raskin A, Tcheou J, Khalil Z, van de Guchte A, Farrugia K, Khan Z, Kelly G, Srivastava K, Eaker L, Bermúdez González M, Mulder L, Beach K, Fatou B, Smolen K, Viode A, van Haren S, Jha M, Kho A, Milliren C, Chang A, McEnaney K, Barton B, Lentucci C, Murphy M, Saluvan M, Shaheen T, Liu S, Syphurs C, Albert M, Hayati A, Bryant R, Abraham J, Salehi-Rad R, Rivera A, Sen S, Elashoff D, Ward D, Presnell S, Kohr B, Arnett A, Boddapati A, Tharp G, Pellegrini K, Johnson B, Panganiban B, Huerta C, Anderson E, Samaha H, Sevransky J, Bristow L, Beagle E, Cowan D, Hamilton S, Hodder T, Esserman D, Brito A, Rothman J, Grubaugh N, Ko A, Hafler D, Shaw A, Gygi J, Pawar S, Konstorum A, Chen E, Cotsapas C, Wang X, Xu L, Dela Cruz C, Iwasaki A, Mohanty S, Nelson A, Zhao Y, Farhadian S, Asashima H, Pulendran B, Nadeau R, Rosenberg-Hasson Y, Leipold M, Sigal N, Rogers A, Fernandez A, Manohar M, Do E, Chang I, Vita R, Westendorf K, Corry D, Kheradmand F, Song L, Nelson E, Baden L, Mendez K, Lasky-Su J, Tong A, Rooks R, Sekaly R, Fourati S, McComsey G, Harris P, Sieg S, Ribeiro S, Overton J, Rahman A, Hutton S, Michelotti G, Wong K, Seyfert-Margolis V, Metcalf J, Agudelo Higuita N, Sinko L, Booth J, Messer W, Hough C, Siegel S, Sullivan P, Lu Z, Kraft M, Bime C, Mosier J, Erickson H, Schunk R, Kimura H, Conway M, Atkinson M, Brakenridge S, Ungaro R, Manning B, Oberhaus J, Guirgis F, Borresen B, Anderson M. Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology. Science Translational Medicine 2024, 16: eadj5154. PMID: 38630846, DOI: 10.1126/scitranslmed.adj5154.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPro-inflammatory genesViral clearanceUpper airwayImmune signaling pathwaysInduction of pro-inflammatory genesBiomarkers of disease severityDelayed viral clearanceImpaired viral clearanceSevere coronavirus disease 2019B cell populationsAge-dependent up-regulationExpression of pro-inflammatory genesHost immune responseSignaling pathwayType I interferon gene expressionCOVID-19 immunopathologyInnate immune signaling pathwaysSerum chemokinesAge-dependent impairmentNaive TMulticenter cohortNasal transcriptomeAcute respiratory syndrome coronavirus 2Monocyte populationsSerum protein profilesDevelopmental changes in lung function of mice are independent of sex as a biological variable
Bärnthaler T, Ramachandra A, Ebanks S, Guerrera N, Sharma L, Dela Cruz C, Humphrey J, Manning E. Developmental changes in lung function of mice are independent of sex as a biological variable. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2024, 326: l627-l637. PMID: 38375577, DOI: 10.1152/ajplung.00120.2023.Peer-Reviewed Original ResearchCitationsAltmetricConceptsPulmonary function testsWeeks of ageStatic complianceMale miceInspiratory capacityLung functionBody weight-basedHuman lung pathologiesLung function of miceFemale C57BL/6J miceLung function parametersSex-dependent changesFunction of miceMeasures of lung functionIndependent of sexPreclinical modelsFemale miceC57BL/6J miceLung pathologyFunction testsMiceWeight-basedLungLung disease researchWeeks
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 NHLBI, LCMI Study Section
Peer Review Groups and Grant Study SectionsChairDetails2020 - 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
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Pulmonary, Critical Care & Sleep Medicine
PO Box 208057, 300 Cedar Street
New Haven, CT 06520-8057
United States
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