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.
Wishing Dr. James Tsay and his brilliant team a warm welcome to the A Breath of Hope family.
Progress Reports: Dr. Jun-Chieh (James) Tsay
February 2017 – 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.
Microbes and Lung Cancer
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.