About

Richart William Harper, M.D., is a Professor of Medicine at UC Davis Health within the Department of Internal Medicine. He specializes in the diagnosis and management of patients with critical illness and diffuse parenchymal lung diseases, with a particular focus on sarcoidosis. Dr. Harper also provides expertise in cardiopulmonary exercise testing to diagnose patients with unexplained shortness of breath or to assess response to therapy. His research includes the study of mucosal innate immunity and allergic responses, specifically investigating mechanisms critical for neutrophil recruitment in the airway epithelium. His academic background includes a B.S. in Physics from UC San Diego, an M.D. from Georgetown University School of Medicine, and postgraduate training in internal medicine, pulmonary, and critical care medicine at UC Davis Medical Center. Dr. Harper has received multiple awards for teaching excellence and has contributed to research published in various scientific journals.

Research topics

• Medicine
• Internal medicine
• Pediatrics
• Surgery
• Pathology
• Immunology

Selected publications

• Effect of Repeated Jet Fuel Exposure on Human Bronchial Epithelial Cells as Measured by VOCs

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

  article

  Abstract Rationale Chronic low-level exposure, below permissible exposure limits, to jet fuel, may contribute to deployment related lung disease. Previous studies demonstrated increased oxidative stress, acute inflammation, and IL-8 levels from human bronchial epithelial (BAE) cell cultures after 8 hours of exposure that normalized over 48 hours, with a volatile organic compound (VOC) emission profile demonstrating a similar response. Given the change in inflammatory profiles after a single 8-hour exposure, we hypothesize that chronic exposure of JP-8 jet fuel will lead to permanent changes in the inflammatory profiles that are mimicked in the VOC profiles, thus leading to pathways of therapeutic interest. Methods BAE cells were obtained from Lifeline Cell Technology and plated on Transwell chambers (12 mm) at 1-2 × 104 cells/cm2 coated with 0.05mg/mL type IV collagen (Sigma) in the PneumaCult-Ex medium (Stemcell Technologies). BAE cultures were transferred to ALI culture conditions with the appropriate media (Stemcell Technologies) for 1 month after confluence was achieved. BAE cultures were exposed to JP-8 (TAFB) at 0.1 µL/mL concentrations for 8 hours per day for a total of 5 days. Media was changed after every exposure, and samples were taken daily prior to the new exposure and at 24 and 48 hours after the workweek exposure was completed to assess oxidative stress by the GSSG assay, and acute cellular inflammation using amphiregulin. Simultaneously, Transwells containing the JP-8 exposed cells were placed into glass jars filled with 5mL of the appropriate media and capped with lids with sorbent coated Twisters magnetized to them. VOCs absorbed to the Twisters were collected and measured at the same intervals using GC-MS. Results JP-8 exposure over a workweek had a persistent increase in oxidative stress as demonstrated by the GSSG assay (Figure 1A). Amphiregulin assays demonstrated a robust response in the early week of exposure, but this response waned significantly by the end of the week (Figure 1B-C). The amphiregulin response in mimicked in control, however this may suggest that the BAE cells are attempting to repair itself, given the effect of amphiregulin on the epidermal growth factor receptor (EGFR). Though these results were not statistically significant, they do suggest that exposure to JP-8 jet fuel induces cellular injury and repair. Conclusions Chronic exposure to JP-8 fuel, mimicking a workweek, resulted in persistent changes in oxidative stress and acute inflammation. Further studies into the pathways of inflammation are required.

  PublisherDOI

• Low TET1 Expression Levels in COPD Are Associated with Airway and Blood Neutrophilia

  medRxiv · 2025-04-16

  preprintOpen access

  Epigenetic dysregulation, particularly DNA methylation variations, is implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Ten-eleven translocation (TET) proteins (TET1, TET2, and TET3) regulate DNA methylation and gene transcription. Impaired TET1 expression was previously associated with airway inflammation and asthma. Here we investigated TET gene associations with COPD severity. We found that reduced TET1 expression in peripheral blood mononuclear cells was associated with higher sputum and blood neutrophil counts, decreased lung function and increased disease severity in patients. These findings support a potential protective role and warrant further mechanistic investigations into the actions of TET1 in COPD.

  PublisherOA PDFDOI

• Low TET1 Expression Levels in COPD Are Associated With High Numbers of Neutrophils and Surfactant Protein Serum Leakage

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

  article

  Abstract Rationale: Emerging evidence supports that epigenetic dysregulation, specifically variations in DNA methylation, is implicated in chronic obstructive pulmonary disease (COPD). Genes related to oxidative stress, mucus production, and epithelial barrier integrity are under strong epigenetic control. Ten-eleven translocation (TET) proteins, known to catalyze the hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine, may play a significant role but their specific functions in COPD remain underexplored. We aimed to examine the relationship between TET gene expression and COPD clinical phenotypes, with a focus on inflammatory parameters. Methods: RNA-seq data from peripheral blood samples of former smoker COPD patients (n=17; 63-76 yrs old; 40% female) and healthy controls (n=15; 37-43 yrs old, 50% female) was evaluated. Correlations between TET1, TET2, and TET3 expression and immune cell counts, lung function, and COPD severity markers were assessed. Logistic regression and causal inference analyses were used to explore potential associations of TET1 with COPD. Results: TET1 expression was significantly downregulated in peripheral blood mononuclear cells of COPD patients. TET1 showed significant negative correlations with neutrophil counts in sputum and blood as well as with serum SP-D levels, a biomarker linked to COPD severity. Logistic regression indicated that higher TET1 expression was associated with reduced odds of COPD (OR=0.5201). In contrast, blood TET2 and TET3 were positively associated with neutrophil levels, and TET2 was inversely correlated with lung function (FEV1/FVC ratio). Causal inference analysis suggested that TET1's protective effect might be mediated through regulation of neutrophil levels. Conclusion: Our findings highlight a potential protective role for TET1 in COPD through the regulation of neutrophil counts, and serum SP-D, key indicators of airway inflammation severity. TET2 and TET3 on the other hand, were positively associated with inflammatory markers and negatively associated with lung function in COPD. This study suggests that members of the TET family may differentially regulate airway inflammation and may serve as novel epigenetic therapeutic targets in COPD.

  PublisherDOI

• Transplant Donor Evaluation and The Quartz Quandary, Silica or Sarcoidosis

  Preprints.org · 2025-08-15

  preprintOpen access

  Selecting donor organs is both a science and an art. The calculus is often complex evaluating recipients’ acute needs and the quality and risks of the donor organs. Sarcoidosis is usually a disease of exclusion and considered an idiopathic inflammatory granulomatous process frequently in the lung but often with multiorgan involvement. New insights into the interplay between the environmental or occupational antigens and the susceptible genetic host in sarcoidosis have come to light. One such occupational antigen with mixed data regarding the risk of developing sarcoidosis after exposure is silica dust. Despite strict exposure limitations enforced in the United States and several other governing bodies worldwide, clusters of silicosis are on the rise due to engineered stone (quartz), which contain silica particles that when cut can create a dust that can exceed exposure limitations. Data on the quartz-sarcoidosis relationship is minimal, and thus questions exist regarding the risk of silica dust exposure and the risk of sarcoidosis. Silicosis tends to only affect the lungs, preventing them usually from being transplanted while sarcoidosis is recognized as having a high probability of multiple organ involvement. An index case discovered during organ recovery highlights the possible association between silica exposure and sarcoidosis. This case also examples the complexity of donor organ evaluation and the challenges in organ procurement from exposed individuals.

  PublisherOA PDFDOI

• Systematic data capture reduces the need for source data verification: exploratory analysis from a phase 2 multicenter randomized controlled platform trial

  Communications Medicine · 2025-10-29

  articleOpen access

  BACKGROUND: The COVID-19 pandemic gave rise to clinical trials focused on systematic, accurate primary data capture, and reduced reliance on source data verification (SDV). Here, we report on a natural experiment that allowed us to assess the quality, cost, and impact of this approach compared to traditional SDV. METHODS: The I-SPY COVID trial (NCT04488081) was a multicenter, open-label, platform trial that employed a streamlined daily checklist, daily capture of labs and medications, and centralized monitoring to ensure accurate data collection in lieu of SDV. The trial enrolled 1,111 patients in 11 drug arms with severe COVID-19. After the trial arms were closed, extensive retrospective SDV was performed on 333 (30.0%) patients, including 10,101 of 44,486 (23%) electronic case report forms (eCRFs), allowing us to evaluate the impact of our strategy on data integrity, outcomes, and costs. RESULTS: We find that retrospective SDV results in changes to 0.36% (1,234 / 340,532) of data fields. It results in no changes to the type of outcome recorded (death, recovery, or censored), but changes in the day of recovery in 9 instances, by a median of 2 days (range 1-7). Two additional AEs are added during SDV that had not previously been captured. Costs associated with retrospective SDV of 23% eCRFs are 61,073 person-hours at a cost of $6.1 M. CONCLUSIONS: Extensive SDV does not change any results or conclusions of the I-SPY COVID trial, which was designed with a systematic strategy for data capture, monitoring, and safety. This strategy could improve the efficiency of clinical trials and eliminate the need for manual SDV.

  PublisherOA PDFDOI

• Bioreactor contamination monitoring using off-gassed volatile organic compounds (VOCs)

  Analytical and Bioanalytical Chemistry · 2024-12-26 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• In Vitro Volatile Organic Compound Profiling of Human Airway Epithelial Cells in Response to Environmental Exposures

  2024-04-30

  article
  PublisherDOI

• Using the ROX Index to Predict Treatment Outcome for High-Flow Nasal Cannula and/or Noninvasive Ventilation in Patients With COPD Exacerbations

  Respiratory Care · 2024-04-23 · 5 citations

  articleOpen access

  BACKGROUND: /breathing frequency) has been shown to predict risk of intubation after high-flow nasal cannula (HFNC) support among adults with acute hypoxemic respiratory failure primarily due to pneumonia. However, its predictive value for other subtypes of respiratory failure is unknown. This study investigated whether the ROX index predicts liberation from HFNC or noninvasive ventilation (NIV), intubation with mechanical ventilation, or death in adults admitted for respiratory failure due to an exacerbation of COPD. METHODS: We performed a retrospective study of 260 adults hospitalized with a COPD exacerbation and treated with HFNC and/or NIV (continuous or bi-level). ROX index scores were collected at treatment initiation and predefined time intervals throughout HFNC and/or NIV treatment or until the subject was intubated or died. A ROX index score of ≥ 4.88 was applied to the cohort to determine if the same score would perform similarly in this different cohort. Accuracy of the ROX index was determined by calculating the area under the receiver operator curve. RESULTS: A total of 47 subjects (18%) required invasive mechanical ventilation or died while on HFNC/NIV. The ROX index at treatment initiation, 1 h, and 6 h demonstrated the best prediction accuracy for avoidance of invasive mechanical ventilation or death (area under the receiver operator curve 0.73 [95% CI 0.66-0.80], 0.72 [95% CI 0.65-0.79], and 0.72 [95% CI 0.63-0.82], respectively). The optimal cutoff value for sensitivity (Sn) and specificity (Sp) was a ROX index score > 6.88 (sensitivity 62%, specificity 57%). CONCLUSIONS: The ROX index applied to adults with COPD exacerbations treated with HFNC and/or NIV required higher scores to achieve similar prediction of low risk of treatment failure when compared to subjects with hypoxemic respiratory failure/pneumonia. ROX scores < 4.88 did not accurately predict intubation or death.

  PublisherOA PDFDOI

• Effect of Jet Fuel Exposure on Human Bronchial Epithelial Cells as Measured by VOCs

  2024-04-30

  article
  PublisherDOI

• Defining VOC signatures of airway epithelial cells with PM2.5 exposure

  Toxicological Sciences · 2024-10-29 · 3 citations

  articleOpen access

  Volatile organic compounds (VOCs) produced by the lung in response to exposure to environmental pollutants can be utilized to study their impact on lung health and function. Previously, we developed a method to measure VOCs emitted from well-differentiated tracheobronchial epithelial cells in vitro. Using this method, we exposed well-differentiated proximal (PECs) and distal airway epithelial cells (DECs) to varying doses of traffic-related air pollutants (TRAP) and wildfire particulates to determine specific VOC signatures after exposure. We utilized PM2.5 TRAP collected from the Caldecott tunnel in Oakland, CA and the 2018 Camp Fire to model "real-life" exposures. The VOCs were collected and extracted from Twisters and analyzed using gas chromatography-mass spectrometry. Exposure to both types of particulate matter (PM) resulted in specific VOC responses grouped by individual subjects with little overlap. Interestingly the VOCs produced by the PECs and DECs were also differentiated from each other. Our studies suggest that PM exposure induces a specific compartmentalized cellular response that can be exploited for future studies. This response is cell-type specific and potentially related to a phenotype we have yet to uncover.

  PublisherOA PDFDOI

Frequent coauthors

• A. Linderholm

  39 shared

• Nicholas J. Kenyon

  VA Northern California Health Care System

  35 shared

• Timothy E. Albertson

  University of California Davis Medical Center

  25 shared

• Cristina E. Davis

  University of California, Davis

  23 shared

• Tomas Ø. Jensen

  Centre of Excellence for Health, Immunity and Infections

  20 shared

• Mitchell M. McCartney

  VA Northern California Health Care System

  20 shared

• Michael Schivo

  University of California, Davis

  18 shared

• Reen Wu

  18 shared

Labs

• Pulmonary, Critical Care, and Sleep MedicinePI

Education

• Clinical Fellow, Internal Medicine, Division of Pulmonary & Critical Care Medicine

  University of California Davis Medical Center

  1999

• Resident, Internal Medicine

  University of California, Davis

  1996

• M.D., Medicine

  Georgetown University

  1993

• BS, Physics

  University of California San Diego

  1988

Awards & honors

• Excellence in Teaching Award, Pulmonary Fellowship Program (…
• Best Attending by Fellowship Program Choice, Pulmonary and C…
• Excellence in Teaching Award, Pulmonary Fellowship Program (…