Announcing an exciting breakthrough in the lung cancer field, former ABOH Fellow (2016-2018) and winner of the Larry Benjamin Early Detection Award, Dr. James Tsay is published, bringing excitement and critical new information to the lung cancer field. To read Dr. Tsay’s article, Lower Airway Dysbiosis Affects Lung Cancer Progression published November 11, 2020 in Cancer Discovery, click on the link above.
The published study was a continuation of the original study funded by A Breath of Hope Lung Foundation where Dr. Tsay’s work led to the detection of a difference in composition of lung microbes in patients with and without lung cancer. In this new study, he went further to see if specific composition of lung microbes correlates with the prognosis and treatment response. Here he was able to show that having oral microbes in the lung seems to correlate with poor prognosis and worsened tumor progression. In a parallel animal model, introduction of these oral bacteria into the lungs of mice also seemed to show decreased survival, increased tumor burden and increased inflammation.
Dr. Tsay’s team is very excited about these findings. They hope to use the knowledge to further their understanding of microbes and lung cancer. Their goal is to find a way to diagnose lung cancer earlier, and in addition, help improve treatment responses in those who are undergoing treatment for lung cancer.
Dr. Tsay shared, “The grant from the A Breath of Hope Lung Foundation has made a huge difference in my career and has allow us to continue our work in this field. Thank you!”
Having recently joined the NYU Pulmonary faculty as researcher and instructor, Dr. Jun-Chieh (James) Tsay dedicates 75% of his full-time professional effort to research. He is happy to receive the A Breath of Hope Research Fellowship/Larry Benjamin Early Detection Award to build on his training and allow time to advance his skills in molecular oncology, whole transcriptomic sequencing, large data set analysis with biostatistics, bioinformatics and leadership skills.
During his time at the Harvard Medical School Department of Cell Biology, Dr. Tsay studied the signaling pathway of epithelial–mesenchymal transition and learned basic laboratory techniques, including construction of adenovirus vectors and tissue culture. He was awarded the Ruth L. Kirschstien National Research Service Award for investigating the field of injury on epithelial cells, specifically the role that cigarette smoke and aryl hydrocarbon receptorshave on the development of lung cancer.
Dr. Tsay’s team is currently part of a large multi-center collaboration: Lung Team Project 2 (LTP2) funded by NIH-NCI, to identify novel biomarkers for early lung cancer detection. Over the last three years, he has been involved with an NIH-NCI funded (PI: Rom) NYU Early Detection Research Network (EDRN) study, a CT scan screening program at the NYU Lung Cancer Biomarker Center. This has been a key learning experience on hypothesis generating, study design, and data analysis of prospective data from a large cohort of over 1500 study subjects (published PLoS One 2012). His biomarker center works closely with Dr. Harvey Pass (co-mentor), Chief of Division of Thoracic Surgery at NYU and other academic centers to develop serum-basedlung cancer biomarkers (published Current Readings 2013). The team’s next collaborative project consistsof a multi-center, multi-disciplinary approach to biomarker discovery involving radiology, pathology, genomic, microbiome and industry technical support.
Dr. Tsay’s research project pertaining to the A Breath of Hope Research Fellowship focuses on a distinct lung microbiome that exists in health and disease states. The lung, once thought sterile, has been shown to contain microorganisms which exist in far less richness than that of the skin and gut. Studies have shown that microbiomes contribute to disease states such as chronic obstructive lung disease (COPD), emphysema, and asthma. Indirect murine evidence suggests that the lung microbiome may play an important role in the carcinogenesis of lung cancer, with evidence to suggest that the dysbiosis of the lung microbiome worsens survival in mice.
In human subjects, the lung microbiome in diseases such as cystic fibrosis and late-stage COPD has been described in lung explants. Lessons from the gut microbiome have found Fusobacterium Nucleatum in a subset of human colorectal carcinomas. Kostic et al. showed that this species of Fusobacterium Nucleatum in mouse models potentiates a pro-inflammatory phenotype and increased tumor multiplicity. The enrichment of Fusobacterium Nucleatum was associated with tumor-infiltrating myeloid cells. The lung microbiome represents an under-analysed ecological community. Understanding the progression and the development of a malignant phenotype of a microbiome associated with lung cancer can help us not only explore the associations of the lung microbiome community, but may also uncover possible contributions and interventions in order to change the pathogenesis of lung cancer.
Dr. Tsay believes that there is a unique microbiome that is associated with the malignant phenotype of subjects with lung cancer. The aim of this project will be to analyze the distinct microbiome in different lung malignancies, to further describe in taxanomic and metagenomic detail the possible microbiome communities associated with each disease state, and to build a methodological framework in which to address possible contributors to the pathogenesis of lung cancer.
Progress Reports: Dr. Jun-Chieh (James) Tsay
Microbes and Lung Cancer
We are excited to report progress on our project to study the lung microbiome in lung cancer patients. In the first six months, we have been recruiting patients who present to our hospital for bronchscopic evaluation of their lung lesions. These patients have been excited to participate in our project and have provided their consent to have airway brushing samples collected for sequencing of microbes that may reside in our body. Using new sequencing technology, we are able to detect the tiniest amount of microbes in our lung by looking for microbes’ DNA.
We have also been working closely with our bioinformatics statisticians in developing a new way to analyze large amount of data to see what the interaction is between the human host and the lung microbes. We hope this information will give us a new way to detect and treat lung cancer in the near future.
We are excited to report progress on our project to study the lung microbiome in lung cancer patients. In our first year, we have recruited patients who present to our hospital for bronchoscopic evaluation of their lung lesions. Using new sequencing technology, we are able to detect the tiniest amounts of microbes in our lung tissues, by looking for microbes’ DNA. We have analyzed these data that show that different areas of the lung have different microbes.
It appears that in the area that is away from the lung cancer (opposite side of the lung), there is a larger difference in the type of microbe lung cancer patients have compared to subjects without lung cancer. We are also able to show that the human body reacts differently to the different types of microbes in our lung.
Our next step is to show that having a specific type of microbe in our lung will cause a specific reaction by our body, and possibly be one of the reasons why some smokers are more likely to develop lung cancer while others are less likely. Our goal is use this knowledge to help us develop a test that will detect specific microbes that warn patients if they are at risk or may have lung cancer.
Our lab was invited to give an oral presentation of these findings at the American Thoracic Society International Meeting in Washington D. C. this past May.
We are pleased to report progress on our project to study the lung microbiome in lung cancer patients. Over the last 18 months, we have met many altruistic patients who have agreed to donate samples for us to study this exciting project. Using the newest sequencing technology, we can detect the tiniest number of microbes in the lung of these patients to look for microbes’ DNA.
Our initial findings in this project suggest that those with lung cancer have more live bacteria in the lung than those without lung cancer. Some of these bacteria that we have sequenced are usually found in our mouth (common mouth bacteria that everyone has), suggesting that somehow these bacteria are either being aspirated or not being cleared by our body. While the amount is minuscule, we are starting to see that it may be a useful technique to differentiate those with and without lung cancer.
One of our strongest signals is that those with lung adenocarcinoma (subtype of lung cancer) have the biggest difference in microbiome composition when compared to those without lung cancer. We will continue to focus on this subtype of lung cancer. We are also excited to report that we are working to recruit patients who are never smokers that have developed lung cancer and sequence their samples for similar analysis, which is an important next step to our overall goal.
It is still our goal to develop an early detection microbe test that warns people if they are at risk for lung cancer or may already have lung cancer.
Finally, we here at NYU Lung Cancer Biomarker Lab would like to thank all the “A Breath of Hope” donors who have contributed to help our research project and our shared goal in fighting lung cancer. Your gift has been instrumental in my career and our progress as a research team.