Research
Our lab studies the biology of early lung cancer and translates that biology into blood-based tests that can find cancer sooner — spanning basic mechanism, biomarker discovery, and clinical validation.
Overview
Dr. Ostrin is a physician-scientist with a long-standing interest in early lung cancer biology, including basic science research on protein processing and metabolomic alteration during lung carcinogenesis, and translational and clinical research on blood-based biomarkers for the early detection of lung cancer. This work has culminated in a four-protein biomarker panel for lung cancer risk assessment and a ten-protein panel for multi-cancer risk assessment, both moving toward availability as clinical tests. As these biomarkers mature, the lab is closely involved in prospective trials of biomarker-directed cancer screening.
Blood-Based Biomarker Panels
Four-Protein Lung Cancer Risk Panel
A validated protein biomarker panel for lung cancer risk assessment, shown to classify indeterminate pulmonary nodules and to carry mortality-benefit implications when applied to large screening cohorts (PLCO, NLST).
Ten-Protein Multi-Cancer Panel
An expanded panel for multi-cancer risk stratification, currently in validation within lung cancer screening cohorts, with the goal of clinical availability in the near term.
Biomarker Trajectories
Longitudinal modeling of how biomarker levels change over time to enable earlier detection than a single measurement allows.
Indeterminate Pulmonary Nodules
Applying blood-based panels to guide clinical decisions for patients with indeterminate nodules found on imaging, reducing unnecessary biopsies and delays.
Mechanistic & Basic Science Research
- Kynurenine pathway & kynureninase (KYNU): Investigating how NRF2 pathway activation upregulates KYNU, driving tumor immunosuppression and worse outcomes in lung adenocarcinoma.
- Immunoproteasome biology: Characterizing how immunoproteasome deficiency relates to a mesenchymal phenotype, restricted antigen presentation, and poor prognosis in non-small cell lung cancer.
- Extracellular vesicles & plasma proteomics: Profiling circulating microRNAs and plasma-derived extracellular vesicle proteins as sources of early-detection biomarkers.
- Premalignant progression: Studying the transition from airway and alveolar precursor states to invasive lung adenocarcinoma, including work supporting the ATS Research Statement on Premalignant Progression in the Lung.
Current Studies & Collaborations
- The LEAP Study — a multicenter biospecimen and imaging resource supporting validation of liquid biomarkers in a lung cancer screening cohort.
- MD Anderson/UPMC Lung Clinical Validation Center — part of the NCI Early Detection Research Network (EDRN), validating biomarkers for lung cancer early detection.
- PLCO & NLST Cohorts — retrospective validation of biomarker panels and modeling of mortality benefit and screening comorbidity impact.
- Physicians’ Health Study — validation of the blood-based protein biomarker panel for risk assessment of lethal lung cancer.
Funding
Current and recent support for this work includes:
| Agency | Role | Project | Type |
|---|---|---|---|
| NIH / NCI | Principal Investigator | Validation of blood-based biomarkers for risk assessment of lung cancer among individuals with no smoking history in the PLCO cohort | U01CA295902 |
| CPRIT | Principal Investigator | Blood-based biomarkers to guide clinical decision making with indeterminate pulmonary nodules | RP250269 |
| NIH / NCI | Co-Investigator | Clinical Validation Center for Lung Cancer Early Detection (EDRN) | U01CA271888 |
| NIH / NCI | Co-Investigator | Optimizing personalized screening and diagnostic decisions for lung cancer based on dynamic risk assessment and life expectancy | R37CA271187 |
| Lungevity Foundation | Co-Investigator | Lung cancer early detection and indeterminate pulmonary nodules | — |
| American Lung Association | Principal Investigator (past) | The role of KYNU upregulation in lung adenocarcinoma | Lung Cancer Discovery Award |