Respiratory lung disorders, such as Bronchopulmonary dysplasia (BPD), Acute Respiratory Distress Syndrome (ARDS) and Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), are among leading causes of death in newborns and infants in the United States. Often this is due to prematurity or congenital lung abnormalities. As such, research in lung regeneration can help improve the health outcomes of children with BPD, ARDS, ACDMPV and other pediatric respiratory disorders.
I’m a senior investigator with long-standing interest in transcriptional regulation for lung development and lung injury or repair. My research and clinical interests include pediatric and adult pulmonary disorders, such as:
- Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV)
- Acute lung injury/Acute Respiratory Distress Syndrome (ALI/ARDS)
- Bronchopulmonary dysplasia (BPD)
- Chronic obstructive pulmonary disease (COPD)
- Non-small cell lung cancer (NSCLC)
In our lab, my colleagues and I are attempting to uncover the molecular mechanisms responsible for lung development and lung regeneration after injury. We are developing new cell-based treatments for pediatric and adult pulmonary diseases. Furthermore, we are working with nanoparticle delivery systems for gene therapy. To advance lung regenerative medicine, we are designing bioengineered lung tissue, which includes embryonic stem cell (ESC)-derived airways, alveoli and vasculature for future medical applications.
Recent discoveries in my lab include:
- Pulmonary cKIT+ endothelial progenitor cells capable of engraftment into hyperoxia-injured neonatal pulmonary vasculature to fuel lung regeneration (Ren et al, Am J Respir Crit Care Med, 2019)
- Several new nanoparticle formulations capable of delivering non-integrating DNA expression vectors and stabilized mRNAs into pulmonary microvascular endothelial cells with high efficiency (Pradhan et al, Am J Respir Critical Care Med, 2019; Bolte et al, Am J Respir Critical Care Med, 2020; Dunn et al, Adv Healthcare Materials, 2018)
- Small molecule compound RCM-1, which inhibits goblet cell metaplasia and lung inflammation in asthma (Sun et al, Science Signaling, 2017)
My postdoctoral training in lung biology influenced my research interests today. Throughout my research career, I have been passionate about finding molecular and cellular mechanisms needed for lung development and lung repair after injury. In my laboratory, my colleagues and I were the first to discover the role of Forkhead Box (FOX) transcription factors FOXF1, FOXM1 and FOXF2 in the lungs. We took part in identifying and characterizing several FOXF1 mutations in ACDMPV patients and generating multiple mouse models for ACDMPV by inserting human FOXF1 mutations into the mouse genome.
Recognition and awards I’ve received include:
- 2003 Scientist Development Award, American Heart Association
- 2005 March of Dimes Basic Research Award
- 2006 Research Scholar Award from American Cancer Society
- 2012–present Editorial Board, Journal of Biological Chemistry
- 2012–present Member of NIH RIBT Study Section
I have more than 20 years’ experience in the pulmonary field and started working for the Cincinnati Children’s Hospital Medical Center in 2007 after moving my lab from the University of Chicago. My research has been published in the American Journal of Respiratory and Critical Care Medicine, Proceedings of the National Academy of Sciences of the USA, Circulation Research and Science Signaling among other journals.
Lung development; cell proliferation; carcinogenesis; transcriptional regulation of gene expression.
Transcriptional regulation of epithelial and endothelial cell functions during lung embryonic development and lung carcinogenesis; winged helix/forkhead box (Fox) proteins and their role in regulating cell signaling pathways required for cellular proliferation, differentiation, motility and survival; identify and increase understanding of currently unknown mechanisms that cause human lung malformations and promote lung cancer formation.
Visit the Kalinichenko Lab.
Professor, UC Department of Pediatrics