Researchers discover disease-causing stem cells in lungs of cystic fibrosis patients

Cells may contribute to lung inflammation and drug resistance

2023-09-27

(Press-News.org) Two nationally recognized experts in cloning and stem cell science from the University of Houston, Wa Xian and Frank McKeon, are reporting that five lung stem cell variants dominate the lungs of patients with advanced cystic fibrosis (CF), and that these variants drive key aspects of CF pathology including inflammation, fibrosis and mucin secretion.

Cystic fibrosis is an inherited and progressive disease that causes long-lasting lung infections and limits the ability to breathe. It is caused by a defect in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR) and affects nearly 40,000 people in the United States. Defects in the CFTR gene lead to the production of abnormally sticky and thick mucus that clogs organs, particularly lungs, causing chronic lung disease marked by infections and inflammation.

Recently introduced drugs known as CFTR modulators act to rescue the function to the mutant CFTR gene and yield remarkable improvements in lung function of CF patients. However, in patients with established lung disease, lung inflammation remains despite treatment with CFTR modulators. This persistence is concerning as inflammation is thought to be a key factor in the progression of CF lung disease.

This gap in CFTR modulator efficacy renders the work of the Xian-McKeon laboratory particularly relevant.

“Using single cell cloning technology that detailed stem cell heterogeneity in lungs from patients with COPD and idiopathic pulmonary fibrosis (IPF), we identified five stem cell variants common to lungs of patients with advanced CF, including three that show hyperinflammatory gene expression profiles and drive neutrophilic inflammation upon xenografting to immunodeficient mice,” said Xian, research professor in biology and biochemistry.

“We found that CFTR-modulating drugs did not suppress the proinflammatory activity or gene expression of the three CF variants that drive inflammation,” reports McKeon, professor of biology and biochemistry and director of the Stem Cell Center, in the American Journal of Respiratory and Critical Care Medicine. “These findings raise the possibility that these inflammatory stem cell variants are the source of the persistent inflammation in patients treated with CFTR modulators.”

If true, their findings suggest that the inflammatory stem cell variants are key targets for drug discovery to augment the major therapeutic advances brought by CFTR modulators. Identifying such lead drugs is a major effort in the Xian-McKeon laboratory, in collaboration with the Center for Drug Discovery, the UH Sequencing Center and colleagues in the Department of Chemistry and the Center for Biotechnology at Texas A&M in the Texas Medical Center.

END

[Attachments] See images for this press release:

ELSE PRESS RELEASES FROM THIS DATE:

Combating distrust online: New GW study explains why current messaging efforts may not be effective

2023-09-27

WASHINGTON (September 27, 2023) - New research led by the George Washington University finds that current mitigation efforts to combat distrust online may not be effective because organizations and governments tackling distrust are only targeting one topic and only one geographical scale. The study shows that online distrust has become a ‘glocal’ phenomenon, meaning that it is spreading with different topics lumped together and mixing both local and global interests. “The key takeaway here is that distrust ...

When needs compete, love trumps thirst

2023-09-27

ITHACA, N.Y. – While many studies have investigated the neuroscience behind how an animal learns to achieve a goal, such as obtaining water when thirsty, none have understood how animals choose between several competing needs – until now. A Cornell University-led study, published Sept. 27 in the journal Nature, used advanced techniques developed by researchers to track the brain’s dopamine reward system and found – for the first time – this system flexibly retunes toward the most important goal when faced with multiple competing needs. In the study, when a lonely and thirsty male zebra finch encountered a female, his thirst waned and ...

NIH awards merit grant for nanofiber research targeting metastatic lung tumors

2023-09-27

Dr. Vanessa Bellat, an assistant professor of chemistry in radiology and an affiliate of the Molecular Imaging Innovations Institute (MI3) at Weill Cornell Medicine, has been awarded a $2 million, four-year R37 MERIT grant from the National Cancer Institute, part of the National Institutes of Health. She will be developing a new therapeutic approach using nanofibers that selectively deliver drugs to the lungs to treat metastatic tumors and testing it in preclinical models. These fibers are made from peptide chains (building blocks that make up proteins) and have a unique 2-dimensional single ...

UTA research: Wildlife loss five times slower in protected areas

2023-09-27

Protecting large areas of land from human activity can help stem the tide of biodiversity loss, especially for vertebrates like amphibians, reptiles, mammals and birds, according to a new study in Nature. In particular, vertebrate population declines were five times slower in conservation areas compared to animals living in areas not protected from development or conversion to agricultural use. “Protected areas take us from a situation in which biodiversity is ebbing away to one where populations are at least close to stable,” said Luke Frishkoff, coauthor of the study and assistant professor of biology at The University of Texas at Arlington. ...

Milestone for novel atomic clock

2023-09-27

An international research team has taken a decisive step toward a new generation of atomic clocks. At the European XFEL X-ray laser, the researchers have created a much more precise pulse generator based on the element scandium, which enables an accuracy of one second in 300 billion years – that is about a thousand times more precise than the current standard atomic clock based on caesium. The team presents its success in the journal Nature. Atomic clocks are currently the world’s ...

NSF backs Rice processor design, chip security research

2023-09-27

HOUSTON – (Sept. 27, 2023) Rice University computer scientists have won two grants from the National Science Foundation to explore new information processing technologies and applications that combine seamlessly co-designed hardware and software to allow for more effective and efficient data stream analysis using pattern matching. Initiated by a Rice seed grant, the projects address the limitations of current computing infrastructure’s ability to process complex, unstructured data streams. A $1.2 million award will ...

St. Jude Children’s Research Hospital unveils the Domino’s Village

2023-09-27

MEMPHIS, Tenn., Sept. 27, 2023 – St. Jude Children’s Research Hospital® and Domino’s®, the largest pizza company in the world, today unveiled The Domino’s Village, a multi-million dollar housing facility for patients and their families. The six-story building that provides more than 307,000 square feet of residential and recreational space was funded by Domino’s as part of a 10-year, historic $100 million commitment to St. ...

U of M Medical School professor receives $3.5 million to develop Tanzanian reproductive health curriculum for those with disabilities

2023-09-27

MINNEAPOLIS/ST. PAUL (09/27/2023) — Kristen Mark, PhD, with the University of Minnesota Medical School, received a $3.5 million grant from the National Institutes of Health to enhance the quality of life for individuals with disabilities in Tanzania through a new project. The research team will train future healthcare providers like nurses, doctors and midwives with the skills and confidence to offer comprehensive sexual and reproductive healthcare services for people with disabilities. “Through doing this research, we will improve the lives of people with disabilities in Tanzania and build in-country capacity ...

How liver cells become scarring, and worse

2023-09-27

Hepatic fibrosis occurs when scar tissue replaces damaged cells in the liver. Over time, accumulating scarring distorts the liver, interferes with its blood supply and may progressively lead to worsening consequences, from cirrhosis to liver failure to liver cancer. In advanced cases, the only treatment is an organ transplant. In a new paper, published online in the journal Cellular and Molecular Gastroenterology and Hepatology, a team of scientists led by corresponding authors David A. Brenner, ...

Does form follow function? Johns Hopkins Medicine researchers advance understanding of why cell parts look the way they do

2023-09-27

Scientists have long understood that parts of cells, called organelles, evolved to have certain shapes and sizes because their forms are closely related to how they function. Now, Johns Hopkins researchers have developed a bacteria-based tool to test whether, as the axiom goes, form follows function. The tool, which researchers say may someday have practical applications in treating illness, works by precisely targeting and dismantling the outer membrane surrounding organelles, and is being made freely available to other scientists. In an interesting twist, say the researchers, the tool may also be able to dismantle aggregated proteins in cells that ...

Researchers discover disease-causing stem cells in lungs of cystic fibrosis patients

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: