Matthew Zinter
University of California-San Francisco, CA·Medicine & Clinical Research
A bone marrow transplant from a donor can cure a child with leukemia, an immune deficiency, or a severe blood disorder, but the treatment is hard on the lungs. Up to 40% of children develop lung injury afterward, from infection, from chemotherapy damage, or from donor immune cells reacting against the recipient's tissue, and this is a leading cause of death after transplant.
- Fields
Medicine & Clinical Research
Microbiology & Immunology
Physiology
- Topics
hematopoietic cell transplant
pediatric critical care
lung injury
- Grants
- 2 known grants, through May 2030
What they work on
- Identify blood correlates of lung injury after pediatric transplant by comparing gene-activity profiles between airway lavage fluid and blood in the same patient, and separating lung-based from non-lung contributors to mortality.
- Catalog the peptides present in the air sacs and test whether key proteins identified in lavage fluid can distinguish lung injury subtypes when measured in blood, as groundwork for a diagnostic test.
- Define the immune cell populations that mark subtypes of post-transplant lung injury using flow cytometry and single-cell RNA sequencing of lavage cells, tracing whether cells are marrow-derived or tissue-resident and of patient or donor origin.
- Test whether over- and under-activation of pulmonary mononuclear phagocytes, the lung's scavenging immune cells, is reversible by stimulating patient cells with lipopolysaccharide and interferon gamma, then adding GM-CSF or IL-10 and measuring cytokine output.
- Determine which pediatric transplant patients have pulmonary fibrosis at the time of airway lavage using biopsy, pulmonary function tests, and chest imaging, and find lavage gene-expression and protein signatures that distinguish them from patients without fibrosis.
- Follow transplant patients without fibrosis for 12 months to see who develops it, then search their original lavage and blood samples for transcriptomic and proteomic predictors of future pulmonary fibrosis.
More about the research
There is a puzzle at the center of it: these patients have high levels of inflammation throughout the body, yet they struggle to fight off infections in the lung, suggesting the immune system is simultaneously overactive and failing. Meanwhile, doctors diagnose lung injury mostly from indirect signs — cough, fever, cloudy areas on a chest X-ray, blood inflammation markers — none of which reveal what is actually happening in the lung. Both projects here address that gap by studying fluid washed directly out of the airways, using bronchoalveolar lavage, paired with blood samples from the same children, alongside samples from non-transplant controls.
Why it matters
Roughly 100,000 bone marrow transplants are performed worldwide each year, including over 12,000 in U.S. children in a recent five-year span, and lung injury afterward causes breathlessness, lost quality of life, and early death. Identifying the immune pathways and molecular signatures involved could yield bronchoalveolar lavage and blood-based diagnostic tests that distinguish lung injury subtypes, flag children at risk for pulmonary fibrosis who might benefit from new anti-fibrotic drugs, and point to cellular targets for lung-specific treatment.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Timothy Blackwell
University of Michigan, MI·Medicine & Clinical Research
Detect gene activity biomarkers of pre-clinical disease in asymptomatic relatives of familial pulmonary fibrosis patients, using single-cell RNA sequencing of blood immune cells such as CD14+ monocytes alongside high-resolution CT findings.
Hong-Long Ji
Loyola University Chicago, IL·Medicine & Clinical Research
Rank the leading predictors of death in alcoholic and nonalcoholic ARDS patients across 1,204 clinical variables from NIH-funded clinical trials, combining random forest models with SHAP, a method that shows each variable's influence.
Xuefang Cao
University of Maryland, Baltimore, MD·Microbiology & Immunology
Determine whether blood-forming stem and progenitor cells use the receptor CD27 to directly suppress donor T cells, using transplants into Rag1 knockout mice that lack CD27 and NK cells, in vivo and in vitro.
The school
University of California-San Francisco: 89 labs on PI Pages, $2.1B a year on research, 164 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.