The links between lung cancer and the invisible particles that people breathe, from smoke and dust to viruses and bacterial microbes, have been greatly studied over the years.
But research into how one particular particle that’s ubiquitous in the air both indoors and outdoors – microscopic fungi – has been “surprisingly limited” said Joyce Huanhuan Chen, an assistant professor with the UChicago Pritzker School of Molecular Engineering (UChicago PME) and Ben May Department for Cancer Research.
Chen, a lung cancer expert, recently received a prestigious National Institutes of Health MERIT award (a R37 grant), with nearly $2.8 million for the initial five years with possibility to extend to seven years, to study how airborne fungi can cause or worsen lung cancer. She will lead an interdisciplinary team including cancer researcher Asst. Prof. Lixing Yang from Ben May, molecular engineer Assoc. Prof. Jun Huang from UChicago PME and pharmacology Prof. Yin Chen from the University of Arizona.
“The relationship between cancer cells and other microbes and viruses has been established for decades or even centuries,” Joyce Chen said. “However, the role that mycobiome fungi in particular play in cancer has not been well-studied, and as a result is not very clear.”
To fill this research gap, the team will use a novel technique Joyce Chen’s lab developed to grow miniature human lung tissue and systems in the lab. This 3D-organotypic lung model, called the iLung, uses pluripotent stem cells to generate multicellular structures that mimic different parts of the lungs, giving better clarity on how real lungs act, interact and react.
In addition, the team pioneered the development of advanced cell culture and mouse models using live fungal spores, as opposed to the typical fungal filtrate/extract researchers often use. Live spores will better mimic the real-world exposure people face every day.
Using real aspergillus spores, one of the most common fungal strains found in human airway and clinical lung cancer samples, on real, albeit lab-grown, lung cells, Joyce Chen hopes to focus on two areas: initiation and progression. Initiation means how exposure to these particles can start a cancer. Progression means how it affects a tumor’s growth.
People breathe up to 5,000 fungal spores per cubic meter of air every day. Normal, uncompromised immune systems flush these particles out within a few days. But people facing lung cancer do not have normal immune systems. Fungal exposure can cause particular reactions that can make cancers worse.
“It’s very similar to other types of fungi-induced disease, for example, asthma or allergies,” Joyce Chen said. “Our observation is eventually they will turn a Type 1 immune response into a Type 2 immune response in tumor microenvironment. A Type 2 response promotes tumor growth progression, especially when the tumor is in a late stage.”
The research is supported by the National Cancer Institute of the National Institutes of Health under Award Number R37CA289715.