Acute coronary syndrome: risk factors, diagnosis and treatment
Lung Disease News
Aug. 11, 2023 — Yoga and breathing control practices, in combination with aerobic training, are particularly key exercises for asthmatic people seeking to improve their lung function, a new peer-reviewed study ...
Aug. 9, 2023 — New findings may lead to relapse-free treatment for a sizeable subgroup of lung cancer patients. In a study in mice, scientists have identified a biomarker that may help physicians select lung cancer ...
Aug. 8, 2023 — Overly active immune cells are often behind lung damage in diseases such as Covid-19. Researchers have developed an RNA agent for a lung spray that slows the activity of these cells, known as ...
July 25, 2023 — Having a food allergy as a baby is linked to asthma and reduced lung function later in childhood, according to a new ...
July 20, 2023 — Omega-3 fatty acids, which are abundant in fish and fish oil supplements, appear promising for maintaining lung health, according to new evidence from a large, multi-faceted study in healthy adults. ...
July 7, 2023 — The mucus in the airways is not as sticky, inflammation in the lungs significantly reduced: Triple combination therapy can achieve these positive, lasting effects in patients with cystic fibrosis ...
June 22, 2023 — Small-cell lung cancer is a particularly aggressive type of tumor with a consistently high mortality rate. In recent years, the research of scientists has significantly contributed to a better ...
June 8, 2023 — The largest and most comprehensive cell map of the human lung has been completed. The Human Lung Cell Atlas reveals the great diversity of cell types in the lung and shows key differences between ...
June 1, 2023 — Researchers have collaborated to refine a cell culture technology platform that grows genetically identical lung buds from human embryonic stem ...
May 24, 2023 — A new study has shown that human T cells have an important role to play in controlling ...
Apr. 21, 2023 — Storing donor lungs for transplant at 10 degrees Celsius markedly increases the length of time the organ can live outside the body according to new ...
Mar. 31, 2023 — A new type of nanoparticle can be administered to the lungs, where it can deliver messenger RNA encoding useful proteins. Researchers hope to use them to develop new treatments for cystic fibrosis ...
Mar. 28, 2023 — Researchers develop a 3D cell culture system to test how inhibiting fibroblast activities can help treat lung cancer. To simulate the tumor microenvironment and mimic real tissues, the team ...
Mar. 17, 2023 — A new study has revealed FDA-approved trametinib and entinostat (which is currently in clinical trials) can be given in tandem to produce fewer and smaller tumors in mice with LKB1-mutated non-small ...
Mar. 15, 2023 — A new study represents a first step towards generating highly detailed 3-dimensional maps of lung tumors using genetically engineered mouse ...
Mar. 13, 2023 — Scientists have discovered why breast cancer cells that have spread to the lungs may 'wake up' following years of sleep -- forming incurable secondary tumors. Their research reveals the ...
Mar. 10, 2023 — One in 10 adults suffer from the debilitating effects of chronic obstructive pulmonary disease (COPD). Research around a new breathing device developed by pulmonologists offers promise for improving ...
Mar. 9, 2023 — Congenital diaphragmatic hernia is one of the deadliest birth defects. To better understand and treat this condition in the future, researchers designed a new cell model in the laboratory and tested ...
Mar. 8, 2023 — Contracting a lower respiratory tract infection in early childhood is associated with a higher risk of dying from respiratory disease as an adult, according to new ...
Feb. 27, 2023 — New research reveals how the relationship between nerves and immune cells in the lungs can contribute to the development of allergic ...
Friday, August 11, 2023
Wednesday, August 9, 2023
Tuesday, August 8, 2023
Tuesday, July 25, 2023
Thursday, July 20, 2023
Friday, July 7, 2023
Thursday, June 22, 2023
Thursday, June 8, 2023
Thursday, June 1, 2023
Wednesday, May 24, 2023
Friday, April 21, 2023
Friday, March 31, 2023
Tuesday, March 28, 2023
Friday, March 17, 2023
Wednesday, March 15, 2023
Monday, March 13, 2023
Friday, March 10, 2023
Thursday, March 9, 2023
Wednesday, March 8, 2023
Monday, February 27, 2023
Thursday, February 23, 2023
Wednesday, February 22, 2023
Wednesday, February 8, 2023
Wednesday, February 1, 2023
Thursday, January 19, 2023
Thursday, January 12, 2023
Monday, January 9, 2023
Thursday, January 5, 2023
Wednesday, January 4, 2023
Wednesday, December 28, 2022
Monday, December 26, 2022
Thursday, December 22, 2022
Wednesday, December 21, 2022
Tuesday, December 6, 2022
Monday, December 5, 2022
Friday, December 2, 2022
Thursday, December 1, 2022
Wednesday, November 30, 2022
Tuesday, November 29, 2022
Tuesday, November 22, 2022
Monday, November 21, 2022
Thursday, November 17, 2022
Wednesday, November 16, 2022
Tuesday, November 15, 2022
Tuesday, November 8, 2022
Thursday, November 3, 2022
Wednesday, November 2, 2022
Wednesday, October 26, 2022
Tuesday, October 25, 2022
Monday, October 17, 2022
Monday, October 10, 2022
Tuesday, October 4, 2022
Tuesday, September 27, 2022
Friday, September 23, 2022
Thursday, September 22, 2022
Monday, September 19, 2022
Friday, September 16, 2022
Thursday, September 15, 2022
Wednesday, September 14, 2022
Tuesday, September 13, 2022
Thursday, September 8, 2022
Tuesday, September 6, 2022
Monday, September 5, 2022
Friday, September 2, 2022
Thursday, September 1, 2022
Wednesday, August 31, 2022
Thursday, August 25, 2022
Thursday, August 18, 2022
Tuesday, August 9, 2022
Monday, August 8, 2022
Tuesday, August 2, 2022
Monday, August 1, 2022
Thursday, July 28, 2022
Wednesday, July 27, 2022
Tuesday, July 26, 2022
Monday, July 25, 2022
Wednesday, July 20, 2022
Monday, July 18, 2022
Thursday, July 14, 2022
Tuesday, July 5, 2022
Wednesday, June 29, 2022
Thursday, June 23, 2022
Tuesday, June 21, 2022
Tuesday, June 14, 2022
Friday, June 10, 2022
Thursday, June 9, 2022
Friday, June 3, 2022
Thursday, June 2, 2022
KSU Researcher Awarded $200K American Lung Association Grant To Study Viral Pneumonia
The American Lung Association Research Institute has awarded $13.6 million in research grants to fund 129 innovative projects to advance science to end lung disease, including a project from Kansas. Pankaj Baral, Ph.D. From Kansas State University was awarded the COVID-19 Respiratory Virus Research Award. For the next two years he will receive $100,000 under the award for a grant total of $200,000.
Lung research is critical because 374,000 Kansans are living with lung disease and each year, millions of people are impacted by respiratory viruses like COVID-19 and influenza. Through the Awards and Grants Program, the Lung Association supports trailblazing research, novel ideas, and innovative approaches. The funded researchers investigate a wide range of lung health topics, including asthma, COPD, lung cancer infectious lung diseases and more.
"We are honored to welcome Dr. Pankaj Baral to the elite American Lung Association Research Institute and our efforts to fundamentally transform lung health here in Kansas & Greater Kansas City and across the nation," said Linda Crider, executive director at the Lung Association. "Our research investment is key to unlocking solutions to alleviate the burden of lung disease. The Lung Association's Awards and Grants Program promotes innovative research, collaboration, translation of discoveries, and scientific exchange to transform today's science into tomorrow's solutions. Because when you can't breathe, nothing else matters."
Dr. Baral's project will investigate how the signaling of sympathetic neurons to immune cells can regulate inflammation and infection outcomes during viral pneumonia. The findings could pave the way for new therapy strategies for fatal pneumonia, acute lung injury, acute respiratory distress syndrome, influenza A and COVID-19. "I would like to thank the American Lung Association for supporting our research to understand how neuroimmune interactions influence the lung immune response to influenza A infection," said Dr. Baral. "Utilizing the interdisciplinary approaches involving neuroscience, immunology and murine pneumonia model, this work helps identify the approaches that directly target the nervous system, or associated molecular receptors, to develop alternative host-based strategies to treat viral pneumonia."
This year, awards were given in different categories addressing many aspects of lung disease; ALA/AAAAI Allergic Respiratory Diseases Award, ALA/ATS/CHEST Foundation Respiratory Health Equity Research Award, Catalyst Award, COVID-19 Respiratory Virus Research Award, Dalsemer Award, Innovation Award and Lung Cancer Discovery Award. Research projects funded by the Lung Association are carefully selected through rigorous scientific peer review and awardees investigate a wide range of complex issues.
The Lung Association's Research Institute includes the Awards and Grants program, and also the Airways Clinical Research Network, the nation's largest not-for-profit network of clinical research centers dedicated to asthma and COPD treatment research. The Lung Association is currently accepting applications for its 2024-2025 research awards and grants cycle.
For more information about the active research funding opportunities, visit Lung.Org/awards.For more information about the new grant awardees and the entire American Lung Association Research Team, visit Lung.Org/research-team.
Media Resources
Get involved and help the American Lung Association's mission. The Fight For Air Climb in Kansas City is coming up this spring on March 3. Learn more at FightForAirClimb.Org/KansasCity.
Human Lung Chip Leveraged To Faithfully Model Radiation-induced Lung Injury
Researchers have developed a human in vitro model that closely mimics the complexities of radiation-induced lung injury (RILI) and radiation dose sensitivity of the human lung. Using a previously developed microfluidic human Lung Alveolus Chip lined by human lung alveolar epithelial cells interfaced with lung capillary cells to recreate the alveolar-capillary interface in vitro, the researchers recapitulated many of the hallmarks of RILI, including radiation-induced DNA damage in lung tissue, cell-specific changes in gene expression, inflammation, and injury to both the lung epithelial cells and blood vessel-lining endothelial cells. By also evaluating the potential of two drugs to suppress the effects of acute RILI, the researchers demonstrated their model's capabilities as an advanced, human-relevant, preclinical, drug discovery platform.
The lung is one of the tissues most sensitive to radiation in the human body. People exposed to high radiation doses following nuclear incidents develop radiation-induced lung injury (RILI), which affects the function of many cell types in the lung, causing acute and sustained inflammation, and in the longer term, the thickening and scarring of lung tissue known as fibrosis. RILI also is a common side effect of radiation therapy administered to cancer patients to kill malignant cells in their bodies, and can limit the maximum radiation dose doctors can use to control their tumors, as well as dramatically impair patients' quality of life.
Anti-inflammatory drugs given to patients during radiation therapy can dampen the inflammation in the lungs, called pneumonitis, but not all patients respond equally well. This is because RILI is a complex disorder that varies between patients and is influenced by risk factors, such as age, lung cancer state, and other pre-existing lung diseases, and likely the patient's genetic makeup. In the event of nuclear accidents, which usually involve the one-time exposure to much higher doses of radiation, no medical countermeasures are available yet that could prevent and protect against the damage to the lungs and other organs, making this a key priority of the US Food and Drug Administration (FDA).
A major obstacle to developing a much deeper understanding of the pathological processes triggered by radiation in the lung and other organs, which is the basis for discovering medical countermeasures, is the lack of experimental model systems that recapitulate how exactly the damage occurs in people. Small animal preclinical models fail to produce key hallmarks of the human pathophysiology and do not mimic the dose sensitivities observed in humans. And although non-human primate models are considered the gold-standard for radiation injury, they are in short supply, costly, and raise serious ethical concerns; they also are not human and sometimes fail to predict responses observed when drugs move into the clinic.
Now, a multi-disciplinary research team at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Boston Children's Hospital led by Wyss Founding Director Donald Ingber, M.D., Ph.D., in an FDA-funded project, has developed a human in vitro model that closely mimics the complexities of RILI and radiation dose sensitivity of the human lung. Lung alveoli are the small air sacs where oxygen and CO2 exchange between the lung and blood takes place, and the major site of radiation pneumonitis. Using a previously developed microfluidic human Lung Alveolus Chip lined by human lung alveolar epithelial cells interfaced with lung capillary cells to recreate the alveolar-capillary interface in vitro, the researchers recapitulated many of the hallmarks of RILI, including radiation-induced DNA damage in lung tissue, cell-specific changes in gene expression, inflammation, and injury to both the lung epithelial cells and blood vessel-lining endothelial cells. By also evaluating the potential of two drugs to suppress the effects of acute RILI, the researchers demonstrated their model's capabilities as an advanced, human-relevant, preclinical, drug discovery platform. The findings are published in Nature Communications.
"Forming a better understanding of how radiation injury occurs and finding new strategies to treat and prevent it poses a multifaceted challenge that in the face of nuclear threats and the realities of current cancer therapies needs entirely new solutions," said Ingber. "The Lung Chip model that we developed to recapitulatedevelopment of RILI leverages our extensive microfluidic Organ Chip culture expertise and, in combination with new analytical and computational drug and biomarker discovery tools, gives us powerful new inroads into this problem." Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
Advanced human in vitro model of RILI
The human Lung Alveolus Chip is a 2-channel microfluidic culture system in which primary human lung alveolar epithelial cells are cultured in one channel where they are exposed to air as they would be in the lung. They are also interfaced across a porous membrane with primary human lung capillary endothelial cells in the parallel channel that are constantly perfused with a blood-like nutrient medium that contains circulating human immune cells, which also can contribute to radiation responses. This carefully engineered, immunologically active, alveolar-capillary interface also experiences cyclic mechanical movements mimicking actual breathing motions. Importantly, this living breathing Lung Chip can be transiently exposed to clinically relevant doses of radiation, and then investigated for the effects over an extended period of time.
When the Lung Alveolus Chip was exposed to increasing doses of radiation, the cell, tissue, and organ-level responses modeled on-chip closely aligned with clinical observations and, importantly, offered new insights into RILI. Following a one-time radiation treatment, the team could observe breaks in the cells' chromosomes with activation of associated DNA repair machinery, whose numbers increased with the amount of radiation applied to the Lung Alveolus Chip. This was paralleled by increased levels of reactive oxygen species that are known to also damage DNA, as well as many other types of molecules. Cells started to increase their size, a phenomenon known as hypertrophy that is commonly seen in alveolar injury in vivo, the barrier comprised by tightly packed endothelial and epithelial cells started to break down and liquid flowed through the endothelial channel accumulated in the epithelial channel.
"Interestingly, we mapped the levels of multiple pro-inflammatory cytokines over a seven-day course following the radiation treatment, which is especially important for assessing oncoming radiation injury to the lung. RILI symptoms in patients only begin to appear after a week following exposure, but the preceding inflammation cannot be captured in patients," said first-author Queeny Dasgupta, Ph.D., who led the project as a Postdoctoral Fellow on Ingber's team, and now is a Scientist at Systemic Bio, a 3D Systems company. "Once overt RILI has manifested itself in patients, it is often too late to rescue the affected lung tissue."
The team found that the first pro-inflammatory cytokines started to be upregulated already 6 hours following the application of high radiation doses, and that their numbers and levels kept increasing until day seven, the end of their observation period. Importantly, this trend was much stronger pronounced in vascular endothelial cells than lung epithelial cells. In parallel, the cellular injury in the Lung Alveolus Chip was reversed in epithelial cells over time but, in contrast, it was sustained in endothelial cells, replicating clinical observations that found RILI to predominantly impact the vascular endothelium in alveoli.
From radiation injury to genes to targets
To more systematically understand the cellular changes triggered by radiation in the Lung Chip, and identify potential drug targets, the researchers analyzed the complete gene expression programs of epithelial and endothelial cells over time. This allowed them to not only further define the cell-specific early and later-stage inflammatory responses, but also to generate whole-genome gene expression data that they could feed into a machine learning-based computational algorithm called "Network Model for Causality-Aware Discovery" (NeMoCAD). NeMoCAD previously enabled Ingber's team to predict therapeutic targets and repurpose drugs that reverse disease states. The analysis led them to home in on a gene called HMOX1, which is involved in an anti-oxidant response, and whose expression was upregulated immediately following radiation exposure and remained elevated throughout the seven-day course of the investigation.
"We found that further increasing HMOX1 levels with the drug lovastatin in the Lung Alveolus Chip reduced DNA damage and cellular hypertrophy early after the radiation, similarly to the anti-inflammatory drug prednisolone, which we used as a positive control. Later, however, lovastatin worsened the disruption of the endothelial barrier. In fact, by experimentally knocking down HMOX1 expression during later stages, we could partially reverse its later adverse effects," explained Dasgupta. "This showed that HMOX1 function indeed is very relevant to the development of RILI, but also suggests that targeting HMOX1 and perhaps targets related to other potential processes might require a more balanced therapeutic approach."
The study is part of a larger campaign at the Wyss Institute aiming to investigate acute radiation damage across several organs and tissues. The group has previously modeled acute radiation injury in Organ Chip models of intestine and bone marrow as well, and each exhibited a different radiation dose sensitivity that matched that of humans. Ingber's team also speculates that radiation damage in one organ might also affect the function of other organs and plans to address this possibility by microfluidically linking different Organ Chips in the future. They also think that the hypersensitivities of patients predisposed by other lung diseases to radiation could be modeled in personalized Lung Alveolus Chips.
Other authors on the study are past and present members of Ingber's team, including Amanda Jiang, Amy Wen, Robert Mannix, Yuncheng Man, Sean Hall, and Emilia Javorsky. The work was funded by the FDA (under grant #75F40119C10098), and the Wyss Institute at Harvard University.
Comments
Post a Comment