# Let-7b in BPD > **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $543,288 ## Abstract Project Summary Bronchopulmonary dysplasia (BPD) is common in extremely low birth weight (ELBW) infants. Recently, we discovered that the strongest biomarker signal was of microRNA let-7b-5p, with a 46-fold increase (p<0.001) at birth in the blood of infants who subsequently developed severe BPD (versus no BPD) many weeks later at 36w post-menstrual age. We also found a 14-fold increase of let-7b-5p on day 1 in the tracheal aspirate of infants who subsequently developed BPD. In cell culture, airway epithelial cells were the primary source of let-7b-5p, that increased with hyperoxia. We found that excessive let-7b inhibits angiogenesis, and that let-7b inhibition during hyperoxia improves lung development in newborn mice. In the “Let-7b in BPD” project, we will build upon our exciting discovery of let-7b-5p as a robust biomarker of BPD, and determine its relevance to lung development and BPD. We will test the central hypotheses that miRNA let-7b-5p is (a) a valuable biomarker for staging, monitoring disease progression and response to therapy, (b) is released from airway epithelial cells by oxidative stress, (c) is a contributor to dysregulated angiogenesis in bronchopulmonary dysplasia, and (d) that inhibition of let-7b signaling improves lung angiogenesis and attenuates the BPD phenotype. We will test the hypotheses by the following Specific Aims: Specific Aim 1 – Determine if plasma let-7b-5p concentrations in extremely preterm infants track with lung disease progression and correlate with response to therapy. Let-7b-5p will be measured in serial plasma samples from a well characterized prospective cohort of 150 extremely preterm infants. We will define the temporal changes in let-7b-5p with respiratory illness severity, BPD staging and lung mechanics at 36w PMA, and with clinical therapies. Specific Aim 2 – Determine the mechanisms of Let-7b release by newborn mouse lung airway epithelium To confirm that the let-7b-5p release by oxidative stress is the key upstream mechanism, we will use novel transgenic mice. We will test the hypothesis that reduction of mitochondrial ROS reduces let-7b-5p and the BPD phenotype, and determine the role of Nrf2 and NF-kB signaling using specific inhibitors/modulators in cell culture models. Specific Aim 3 – Determine effects of excessive let-7b-5p signaling on lung microvascular development. We will test the hypothesis that over-expression of let-7b-5p induces impaired lung microvascular development, inducing a BPD phenotype in newborn mice even in normoxia, and that inhibition of let-7b-5p improves lung development in hyperoxia- exposed newborn mouse lung (BPD model). ## Key facts - **NIH application ID:** 10828007 - **Project number:** 5R01HL156275-02 - **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM - **Principal Investigator:** Namasivayam Ambalavanan - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $543,288 - **Award type:** 5 - **Project period:** 2023-04-14 → 2027-03-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10828007 ## Citation > US National Institutes of Health, RePORTER application 10828007, Let-7b in BPD (5R01HL156275-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10828007. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*