Min-Jong Kang, MD, PhD, MPH, researches the effects of mitochondrial function and regulation of innate immunity on the host immune response, including aging-related immune dysregulation.
An associate professor of medicine (pulmonary), Kang came to Yale School of Medicine more than two decades ago as a visiting scholar. At the time, he was interested in learning how smoking exposure contributed to the pathobiology of chronic obstructive pulmonary disease (COPD) and asthma.
“The fact that smoking exposure impacted certain aspects of the innate immune response, especially the cytoplasmic double-stranded RNA, was against the conventional understanding at the time,” Kang said of his early research. “This led me to focus on the mitochondrial antiviral signaling protein, or MAVS.”
In a Q&A, Kang discusses the role of MAVS in host resilience, aging as a contributing factor of lung disease, and the link between viral innate immunity and aging biology.
Tell us more about the molecule MAVS.
We know that during a microbial infection, the host fights against the pathogen. However, many questions remain unanswered about host resilience. My molecule of interest, MAVS, seems to drive host resilience impairment.
MAVS is located on the outer membrane of the mitochondria and is thus ideally positioned to convey information between the cytoplasm and the mitochondria. Through MAVS, the innate immune signaling pathways are modulated and conveyed. Dissecting these innate immune signaling pathways can help us learn more about mitochondrial regulation of innate immunity.
MAVS is widely studied in viral infections and diseases, including COVID-19. However, a virus is generally not associated with the pathobiology of the diseases I study, such as idiopathic pulmonary fibrosis. Even in these non-viral disease contexts, this virus-related innate immune mechanism plays a critical role.
What have you discovered about the connection between aging and disease?
During aging, when cells are senescent and mitochondrial function deteriorates, mitochondrial nuclei contents like mitochondrial double-stranded RNA or mitochondrial DNA are released outside of the mitochondria into the cytoplasm, where they are recognized as foreigners by the cell. In other words, when these endogenous nucleic acids are located abnormally—or ectopically—they behave like viruses and stimulate the antiviral innate immune pathway, even in a nonviral context.
Aging is one of the greatest risk factors for all non-communicable chronic diseases, which are more prevalent in the aged population compared to the younger population. Diseases I study, such as COPD and idiopathic pulmonary fibrosis, are well-known age-associated lung disorders. The question is how aging hallmarks, which are observed in patients with COPD and IPF, are connected to disease pathobiology.
Where is your research headed?
I am focusing on two aging hallmarks, mitochondrial dysfunction and cellular senescence, as a kind of prism through which to view fundamental biological mechanisms. We know that viral innate immunity and aging biology are married together, but why?
I am working to understand how aging-related lung disorders occur and how we can identify intervention points and potential therapeutics that promote mitochondrial function or alleviate cellular senescence. I hope to find a disease-modifying strategy for COPD and IPF. As a physician-scientist, my goal is to benefit patients.
The Section of Pulmonary, Critical Care and Sleep Medicine is one of the eleven sections within Yale School of Medicine’s Department of Internal Medicine. To learn more, visit PCCSM's website, or follow them on Facebook and Twitter.