About

John A. Belperio, MD, is the Division Chief of Pulmonary, Critical Care & Sleep Medicine at UCLA Health. His role involves leading the division and overseeing clinical and research activities within these specialties. The page highlights his position within the leadership team, emphasizing his leadership responsibilities in pulmonary medicine, critical care, and sleep medicine at UCLA Health.

Research topics

• Internal medicine
• Medicine
• Pathology
• Gastroenterology
• Cancer research
• Immunology
• Genetics
• Biology
• Cardiology
• Surgery

Selected publications

• Expression of complement pathway genes is associated with progression of idiopathic pulmonary fibrosis

  Respiratory Research · 2026-03-25

  articleOpen access

  Studies suggest that the complement pathway may play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We evaluated associations between complement pathway gene expression and clinical outcomes in patients with IPF. RNA was extracted from blood samples collected at enrollment into the IPF-PRO Registry. Patients were divided into discovery (n = 261) and validation (n = 609) cohorts. Patients were followed prospectively while receiving usual care. Using Cox proportional hazards models, we evaluated associations between expression of 45 complement pathway genes and three clinical outcomes. Analyses were unadjusted and adjusted for clinical variables at enrollment. Eight complement pathway genes (CR1, CD59, C2, C1QTNF6, ITGB3, C1QBP, CD55, CR2) were associated with ≥ 1 outcome in the discovery cohort and evaluated in the validation cohort. In the discovery cohort, in unadjusted analyses, higher expression of the membrane-bound complement regulators CR1, CD55, and CD59 was associated with increased risk (hazard ratios [HRs]: 1.75 [95% CI 1.27, 2.41], 1.40 [1.06, 1.85] and 1.62 [1.17, 2.23], respectively), and higher expression of complement pathway component C2 with a decreased risk (HR 0.75 [0.61, 0.91]), of disease progression (absolute decline in forced vital capacity % predicted ≥ 10%, death, or lung transplant). Associations of CR1, CD55 and C2 with disease progression persisted in the validation cohort in adjusted analyses. In the discovery cohort, in unadjusted analyses, higher expression of CR1 and CD55 was associated with increased risk (HRs 2.66 [1.68, 4.23] and 1.90 [1.24, 2.93], respectively), and higher expression of C2 with a decreased risk (HR 0.61 [0.46, 0.80]), of respiratory death; associations with CR1, CD55, and C2 persisted in the validation cohort in adjusted analyses. In the validation cohort, increased expression of C2 was associated with reduced risk of respiratory hospitalization in adjusted analyses (HR 0.65 [0.50, 0.83]). Principal component analysis identified a composite score including complement components and regulators that was associated with increased risk of disease progression and respiratory death in both cohorts. Higher expression of complement regulators and lower expression of complement components, individually and in combination, may be biomarkers of progression of IPF. ClinicalTrials.gov (NCT01915511). Registered 5 August 2013, https://clinicaltrials.gov/ct2/show/NCT01915511.

  PublisherDOI

• Utility of donor-derived cell-free DNA testing after lung transplantation in the precision medicine era

  The Journal of Heart and Lung Transplantation · 2026-04-01

  article
  PublisherDOI

• Proteomic Immune Signatures of Severe HIV-Associated Tuberculosis in Sub-Saharan Africa: A Prospective, Multicenter Analysis from Uganda

  medRxiv · 2026-01-02

  articleOpen access

  Abstract Objective Severe tuberculosis (TB) is a major cause of critical illness and death in people living with HIV (PLWH) worldwide. Despite this, the immunopathology of severe HIV-associated TB (HIV/TB) is poorly understood. We aimed to identify an immunopathologic signature of severe HIV/TB in sub-Saharan Africa. Design and Setting We analyzed proteomic data from two prospective observational cohorts of adults hospitalized with severe undifferentiated infection in Uganda: an urban discovery cohort (Entebbe, N=241) and a rural validation cohort (Tororo, N=253). Patients Adults (age ≥18 years) hospitalized with severe febrile illness Interventions None Measurements and Main Results Across both cohorts, severe HIV-associated TB was common, affecting 18% of participants in the discovery cohort and 21% in the validation cohort. Overall mortality was significant (30-day mortality of 22% in the discovery cohort & 60-day mortality of 26% in the validation cohort). Participants were stratified into three HIV/TB phenotypes: HIV-negative without TB, PLWH without TB, and PLWH with microbiologically diagnosed TB. We applied ordinal random forest models in the discovery cohort to identify proteins strongly predictive of progressive HIV/TB phenotype. In both cohorts, PLWH with microbiologically diagnosed TB were at highest risk of critical illness and death (30-day mortality of 42% in the discovery cohort & 60-day mortality of 52% in the validation cohort). An eight-protein signature reliably distinguished this phenotype, reflecting mediators of macrophage/dendritic cell activation (LAMP3), NK- and T-cell stimulation and cytotoxicity (CD70, CRTAM), B-cell activation (IGLC2), protease-mediated tissue injury (PRSS2), dysregulated coagulation (SERPINA5), extracellular matrix remodeling (EFEMP1), and GH/IGF axis dysregulation (IGFBP3). Conclusions We identified an immunologic signature of severe HIV-associated TB defined by mediators of macrophage/dendritic cell and cytotoxic lymphocyte activation, extracellular matrix remodeling, and dysregulated coagulation. These findings offer new insight into HIV/TB pathobiology and highlight potential targets for host-directed therapies in this high-risk population. Key Points Question What host-response patterns characterize severe HIV-associated tuberculosis among adults hospitalized with severe febrile illness in sub-Saharan Africa? Findings In two prospective cohorts of adults hospitalized with severe febrile illness in Uganda, severe HIV-associated tuberculosis accounted for 18-21% of cases and was associated with higher rates of physiological instability and mortality. An eight-protein host-response signature reproducibly distinguished this high-risk phenotype, reflecting immune activation, tissue injury, extracellular matrix remodeling, and dysregulated coagulation. Meaning Severe HIV-associated tuberculosis is associated with a distinct, high-risk clinical phenotype characterized by reproducible host-response patterns that may inform risk stratification and host-directed therapeutic strategies.

  PublisherOA PDFDOI

• Comparative Effectiveness of Single Versus Bilateral Lung Transplantation in Dually Listed Recipients

  Annals of Surgery · 2026-05-18

  article

  OBJECTIVE: To compare outcomes of single(SLT) versus bilateral(BLT) lung transplantation among dually listed recipients hypothetically eligible for either treatment. SUMMARY BACKGROUND DATA: Considerable debate remains regarding the added benefit of BLT versus SLT. Prior analyses were confounded by significant selection bias or limited in generalizability to the contemporary era; a randomized trial remains unlikely due to ethical concerns. METHODS: Within the Organ Procurement and Transplantation Network, we considered all adults who were dually listed for SLT and BLT and underwent first-time lung allograft transplantation for idiopathic pulmonary fibrosis(IPF) or chronic obstructive pulmonary disease(COPD) in the US between 2017-2024. We applied target trial emulation and clone-censor weight methodology to emulate a prospective randomized trial comparing SLT versus BLT. RESULTS: We tabulated 3,274 dually listed lung allograft recipients, of whom 1,026 were transplanted for COPD and 2,248 for IPF. Median follow-up was 24.5 months. COPD patient survival at five years was superior following BLT (61%[55-66%]) versus SLT (52%[46-58%, P=0.009). Meanwhile, among IPF patients, five year survival was 59%[54-63%] following BLT versus 56%[51-61%], P=0.009) after SLT. In a target trial emulation, among COPD patients, BLT remained associated with reduced mortality hazard (HR 0.67, CI 0.50-0.88). However, stratifying by age, SLT and BLT yielded comparable outcomes among patients ≥70years (HR 0.75, Credible Interval 0.38-1.37). Evaluating IPF recipients, after adjustment, BLT remained associated with comparable mortality hazard (HR 1.04, CI 0.85-1.26). No age-related effect was noted. CONCLUSIONS: Our findings suggest SLT could yield acceptable post-transplantation survival in select patients, while expanding access to this invaluable resource.

  PublisherDOI

• A Case of Metformin-Associated Lactic Acidosis Secondary to Obstructive Acute Kidney Injury

  American Journal of Respiratory and Critical Care Medicine · 2025-05-01 · 1 citations

  articleSenior author

  Abstract Introduction: Metformin-associated lactic acidosis (MALA) is a rare though increasingly well-described complication of metformin use characterized by a triad of elevated serum metformin level, acidemia, and hyperlactatemia. Key risk factors include renal insufficiency (especially when acute), hepatic dysfunction, and concomitant alcohol use. Traditional symptoms include nausea, vomiting, diarrhea, and tachypnea. Management encompasses prompt cessation of metformin, exclusion of alternative causes of lactic acidosis, hemodynamic support, and possible renal replacement therapy (RRT). Mortality with MALA remains high, estimated between 30-50%. MALA is best described with acute kidney injury (AKI), with hypovolemia identified as driving the AKI in a vast majority of cases. Here we present a rare case of MALA from obstructive AKI. Case: A 74-year-old man with benign prostatic hyperplasia (BPH) and diabetes mellitus type 2 controlled with metformin monotherapy presents with a day of progressive diarrhea and respiratory distress. Three days prior, he was seen by his primary care physician for worsening urinary hesitancy, presumed related to BPH, and was prescribed tamsulosin. A day later, he was seen in an emergency department reporting anuria. A Foley catheter was placed for BPH related urinary obstruction. Catheter insertion was noted to be traumatic, though flow of urine was unimpaired at discharge. While home, patient noted worsening hematuria with passage of clots and eventual anuria with subsequent progressive diarrhea and respiratory distress that prompted presentation. At admission, patient was afebrile, normotensive, and normoxemic on room air. Exam disclosed tachypnea and suprapubic tenderness. Labs demonstrated AKI (creatinine increased from 0.95 to 5.46 over previous 3 days) and severe lactic acidosis (pH 7.03 and pCO2 of 19 mmHg by venous blood gas, total CO2 6 mmol/L, and lactate 17.87 mmol/L). Foley catheter was replaced and patient was admitted to the intensive care unit for initiation of continuous RRT. Patient without signs of shock to prompt vasopressor initiation and infectious workup remained negative throughout course. Upon initiation of RRT, patient's acidemia and lactatemia normalized within 24 hours. Metformin level was elevated to 24 mcg/mL (therapeutic range 2-4 mcg/mL). A diagnosis of MALA related to obstructive AKI was applied. Discussion: This case highlights the importance of a broad diagnostic and therapeutic approach to lactic acidosis that prioritizes correction of shock and hypoxemia while also considering rare etiologies including pharmacologic toxicity. While MALA is most frequently encountered in constellation with hypovolemia-induced AKI, this case represents one of the rare descriptions of this process with acute urinary obstruction.

  PublisherDOI

• A Novel Murine Carcinogen-Induced Model Recapitulates the Progression and Heterogeneity of Human Lung Adenocarcinoma

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• Multiprotein predictor of short-term mortality in idiopathic pulmonary fibrosis (IPF)

  2025-09-27

  article

  <bold>Introduction:</bold> Biomarkers that help prognosticate short-term outcomes in patients with IPF are needed. <bold>Aim:</bold> Evaluate the extent to which circulating proteins predict short-term death or lung transplant in patients with IPF. <bold>Methods:</bold> The cohort, drawn from the IPF-PRO Registry, included 624 patients. Sixty-seven proteins in domains of inflammation, matrix/epithelial remodeling, and angiogenesis/coagulation were quantified in plasma using multiplexed immunoassay (Myriad RBM). Data were log₂ transformed. A logistic model with elastic net penalty was fit for the outcome of death or lung transplant at 18 months. Proteins, sex, age, smoking status, FVC % predicted, DLCO % predicted, antifibrotic drug use, oxygen use at rest, oxygen use with activity (all assessed at enrollment) were considered as predictors. Data were split 75/25 into train and test sets. The model was developed in the train set and its performance assessed in the train and test sets using C-index. <bold>Results:</bold> The cohort was 74.4% male. At enrollment, median (Q1, Q3) age was 70 (65, 75) years; median FVC % predicted and DLCO % predicted were 69.1 (58.4, 79.4) and 43.2 (33.4, 51.9), respectively; 25.8% took nintedanib and 23.6% took pirfenidone. A set of 23 proteins and 4 clinical factors discriminated death or lung transplant at 18 months with a C-index of 0.87 in the train set and 0.88 in the test set. A model including only the clinical factors had C-indices of 0.78 in the train set and 0.77 in the test set. The proteins most informative to outcome discrimination were uPAR, SP-D, CRP, angiogenin, and IGFBP2. <bold>Conclusions:</bold> Biomarker-inclusive algorithms have the potential to provide meaningful risk stratification for patients with IPF.

  PublisherDOI

• Changes in Circulating ICAM1 and Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

  American Journal of Respiratory and Critical Care Medicine · 2025-05-01

  article

  Abstract Rationale: Intracellular adhesion molecule 1 (ICAM1) is a cell surface glycoprotein induced on endothelial, epithelial, and immune cells in response to inflammatory stimuli. Prior studies showed that circulating ICAM1 was higher in patients with IPF than in controls and that higher ICAM1 was associated with increased mortality risk in patients with IPF. We used data from the IPF-PRO Registry to understand how short-term changes in circulating ICAM1 relate to use of antifibrotic therapy and inform the risk of disease progression. Methods: The cohort included patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months. ICAM1 was quantified by ELISA in plasma collected at enrollment (n=923) and at 6 (+/- 3) months post-enrollment (n=506). Absolute changes in ICAM1 between the enrollment sample and the 6-month sample were described overall and by antifibrotic drug use. Cox proportional hazards models tested the association between absolute change in ICAM1 over 6 (+/- 3) months and disease progression (decline in FVC % predicted ≥10%, death, or lung transplant), assessed over a median of 45.2 months. Models were adjusted for age, sex, FVC % predicted, DLco % predicted, ICAM1 level at enrollment. Models were landmarked at the time of the 6-month sample. Results: Mean (SD) ICAM1 at enrollment was 196.7 (101.4) ug/L. Among 506 patients with an ICAM1 measure at 6 months, 242 had continued antifibrotic therapy from enrollment to the 6-month sample, 158 had initiated antifibrotic therapy during this period, 8 had discontinued antifibrotic therapy during this period, 98 were untreated at both timepoints. Untreated patients experienced a mean (SD) increase in ICAM1 of 13.5 (102.6) ug/L from enrollment to 6 months, whereas those continuing antifibrotic therapy had a mean (SD) decrease in ICAM1 of -8.7 (115.3) ug/L. Patients initiating antifibrotic therapy between enrollment and 6 months had little change in ICAM1 (mean absolute change -1.3 [104.3] ug/L). In multivariable analyses, absolute change in ICAM1 was significantly associated with the risk of disease progression. A 20-unit (ug/L) increase in ICAM1 was associated with a 3% increase in the risk of progression (adjusted HR 1.03; 95% CI 1.01, 1.05; p=0.014). Conclusions: Our results suggest that short-term change in circulating ICAM1 levels in patients with IPF may be different in patients continuing antifibrotic therapy compared with those remaining untreated. Serial measures of ICAM1 may provide information about risk of progression beyond clinical measures and a baseline ICAM1 value.

  PublisherDOI

• Timing of quality of life and lung function changes during the first year following lung transplantation: A multicenter prospective cohort study

  The Journal of Heart and Lung Transplantation · 2025-10-10 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis

  Journal of Visualized Experiments · 2025-05-09 · 1 citations

  articleSenior author

  Interstitial lung disease (ILD) represents a broad spectrum of disorders characterized by the progressive and often irreversible scarring of the lung parenchyma, the most common being idiopathic pulmonary fibrosis (IPF). Several animal models of IPF have been developed, with the bleomycin murine model being the most widely used. Bleomycin is a chemotherapeutic known to induce DNA damage in the alveolar epithelium, resulting in acute lung injury and pulmonary fibrosis in humans. Rodent models of IPF use bleomycin administration via various methods, the most common being intratracheal (IT). Recently, the oropharyngeal aspiration (OA) technique has been shown to be equally efficacious as IT for multiple fibrosing agents, with considerably fewer side effects and an easier route of delivery. This protocol details the OA method of bleomycin delivery into the murine lung and highlights examples of potential downstream applications for data quantification. This methodology offers a simple, quick, and safe way to utilize this widely used animal model for studying the molecular mechanisms underlying IPF.

  PublisherDOI

Recent grants

• NIH Grant R01HL112990

  NIH · $1.8M · 2017

• The UCLA Pulmonary and Critical Care Medicine Scientist Training Program (PCCM-STP)

  NIH · $8.0M · 2003–2030

• NIH Grant K08HL004493

  NIH · $609k · 2006

• Epithelial-Mesenchymal Interactions in Pulmonary Fibrosis and Chronic Allograft Dysfunction (CLAD)

  NIH · $42.5M · 2012–2024

• NIH Grant R01HL080206

  NIH · $2.3M · 2011

Frequent coauthors

• Mark Berneburg

  University Hospital Regensburg

  318 shared

• Robert M. Strieter

  Charlottesville Medical Research

  316 shared

• Thomas Schwarz

  306 shared

• Alexander K. C. Leung

  224 shared

• Alexander K. C. Leung

  199 shared

• Michael P. Keane

  University College Dublin

  170 shared

• Raoul C. M. Hennekam

  University of Amsterdam

  164 shared

• Christie P. Thomas

  163 shared