Vladimir Kalinichenko
University of Arizona, AZ·Physiology
Healthy lungs depend on a dense mesh of microscopic blood vessels wrapped around the air sacs, where oxygen crosses into the bloodstream. In some newborns these capillaries never form properly or are destroyed soon after birth, and the result is high blood pressure in the lung circulation, respiratory failure, and in the most severe cases death within weeks.
- Fields
Physiology
Biomedical Engineering
Genetics
- Topics
bronchopulmonary dysplasia
pulmonary hypertension
alveolar capillary dysplasia
- Grants
- 3 known grants, through May 2029
What they work on
- Determine why P22-F1 PBAE/PEI/PEG nanoparticles home to lung capillary endothelial cells and no other organ, tracing cell-surface binding, uptake into the cell, escape from internal vesicles, and release of the DNA cargo.
- Test whether nanoparticles carrying a minicircle DNA vector for FOXM1, a transcription factor that drives endothelial cell division, regrow lung capillaries, prevent pulmonary hypertension, and improve breathing in mouse and rat models of bronchopulmonary dysplasia.
- Compare how much two capillary cell types, general capillary cells and aerocytes, need FOXM1 during lung repair, using mice in which Foxm1-floxed alleles are deleted in each cell type separately.
- Test whether FEL1, a conserved regulatory DNA element near FOXF1 that is missing in most patients with type 3 Alveolar Capillary Dysplasia, is required for lung endothelial cells to mature, by building a FEL1-deleted mouse model using CRISPR/Cas9 in embryonic stem cells.
- Test whether nanoparticle delivery of FOXF1-stabilizing compounds (TanFe[F] and the HECTD1 inhibitor I3A) into lung capillaries raises FOXF1 protein, boosts newborn blood-vessel growth, and prevents pulmonary hypertension in Foxf1 mutant mouse models of Alveolar Capillary Dysplasia.
- Determine whether nanoparticle FOXF1 gene therapy gives lasting protection from pulmonary hypertension and right-ventricular enlargement after high-oxygen injury in newborn mice and rats, and whether FOXF1 recruits the signaling protein STAT3 onto chromatin to switch on endothelial enhancers.
- Test whether transplanting FOXF1+ general capillary cells, a progenitor subset of lung microvessel endothelial cells, prevents pulmonary hypertension long-term in a mouse model, and whether DLL4/NOTCH signaling is needed for donor cells to make recipient endothelial cells divide and form tubes.
- Produce FOXF1+ general capillary cells from mouse embryonic stem cells, by directed differentiation in culture and in mouse-rat chimeras, and use them as cell therapy in a mouse model of bronchopulmonary dysplasia with pulmonary hypertension.
More about the research
Work in this lab centers on the endothelial cells that line those capillaries: which genetic switches tell them to multiply and mature, why they fail in premature and congenitally affected infants, and whether restoring one key switch can rebuild the vascular bed. Three linked projects pursue this from different angles, with a shared toolkit of mouse and rat newborn models, single-cell sequencing of mouse and human infant lung tissue, and nanoparticles engineered to deliver genes or drugs to lung capillaries alone.
Why it matters
Bronchopulmonary dysplasia with pulmonary hypertension and Alveolar Capillary Dysplasia are newborn lung diseases with few options; the most severely affected infants often die or carry chronic lung problems for life. By testing lung-capillary-selective nanoparticles carrying FOXF1 or FOXM1 genes, FOXF1-stabilizing compounds, and transplantable capillary progenitor cells in mouse and rat models, this preclinical work could point to treatments that rebuild lung blood vessels and lower lung blood pressure, and the targeting data may help design organ-specific delivery for other lung diseases.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Selective Targeting of Alveolar Capillaries in Neonatal Lung Injury
NIH · Sep 2025 – May 2029
Development of novel therapeutic approaches for treatment of Alveolar Capillary Dysplasia
NIH · May 2021 – May 2029
Transcriptional Regulation of Endothelial Cells after Neonatal Lung Injury
NIH · Apr 2018 – Jun 2027
Closest labs
Thomas Raffay
Case Western Reserve University, OH·Medicine & Clinical Research
Determine the molecular mechanisms by which GSNO protects the newborn lung, using GSNOR knockout mice exposed to high oxygen as a model of bronchopulmonary dysplasia.
Maria Basil
University of Pennsylvania, PA·Medicine & Clinical Research·Early-career
Test whether Notch signaling, a cell-to-cell communication pathway, controls the identity of respiratory airway secretory cells (RASCs) and their ability to produce alveolar type 2 cells, using human embryonic stem cell models.
Andrew Dylag
University of Rochester, NY·Medicine & Clinical Research·Early-career
Determine how the oxygen-rich newborn lung environment drives recruitment and seeding of lung megakaryocytes, by exposing mice to low-dose hyperoxia at different developmental ages and depleting these cells.
The school
University of Arizona: 36 labs on PI Pages, $1.0B a year on research, 487 research doctorates a year.
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