Segal Lab Research | NYU Langone Health

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Segal Lab Segal Lab Research

Segal Lab Research

Early Chronic Obstructive Pulmonary Disease (COPD)

Although lower airway colonization with pathogens has been well known to occur in advanced stage COPD, little is understood about the possible effects of dysbiosis of the lung microbiome in the pathogenesis of COPD. Our current projects seek to dissect the influence of the lung microbiome in the lower airway inflammatory tone that leads to airway injury and inflammation in early phases of this disease. Further, the potential contributions of lower airway dysbiosis to the susceptibility to pathogens is not known in this disease. Our research focuses on obtaining samples from smokers with and without COPD to perform extensive microbiome and host immune profile. In addition, we conduct in-vitro and in-vivo experiments on preclinical models to mechanistically evaluate how lower airway dysbiosis contributes to the pathogenesis of this disease.

Lung Cancer

Despite the declining prevalence of smoking in the U.S., lung cancer continues to be the leading cause of cancer deaths. Treatment of lung cancer with immunotherapy, such as PD-1 blockers, has become first line therapy for most non-small cell lung cancers but has variable effectiveness. It is still unclear what factors determine individuals’ response to immunotherapy. Our lab has demonstrated that lower airway microbiota signatures are associated with host immune tone and that there is a dysbiotic signature associated with upregulation of pro-cancer inflammatory pathways. Our investigations include the use of functional microbiomics and preclinical lung cancer models to uncover how lower airway dysbiosis contributes to the pathogenesis of lung cancer.

Nontuberculous Mycobacteria and Bronchiectasis

The prevalence and associated morbidity is increasing in non-tuberculous mycobacterial infections. The mechanisms of increased susceptibility to these environmental bacteria are not understood and human genetics are poorly associated with this disease suggesting that other environmental factors are likely important. In addition, therapeutic approaches have high toxicity and limited effectiveness. We have described how the lung microbiome of patients with this disease is quite diverse and almost never dominated by Mycobacterium. Thus, our program focuses on the effects of the lower airway microbiome (beyond the known pathogen) on the host immune phenotype as a way to explore for mechanisms leading to increased susceptibility to this environmental microbe.

Mycobacterium Tuberculosis (TB)

Mycobacterium tuberculosis remains the leading infectious cause of death worldwide. The majority of individuals with latent tuberculosis remain symptom-free and non-infectious. However, among those individuals, there is an approximately 12% lifetime risk of developing active TB. Preliminary studies indicate that the microbiome may have a role in the pathogenesis, and that treatment is likely to have an extensive impact on long-term human microbiome diversity. In collaboration with scientists in South Africa, we are interested in exploring changes in the gut and airway microbiome occurring in patients with tuberculosis before and during treatment for active tuberculosis that may explain subjects’ susceptibility to active disease and response to treatment.

Lung Transplantation

In this disease, early mortality is predominantly related to acute transplant rejection and pulmonary infections. Over time, the declining survival rates are primarily attributed to loss in the graft function secondary to chronic lung allograft dysfunction (CLAD). The search for the causes of CLAD in transplant recipients has been elusive. Among known risks factors, early post-transplant events, such as acute rejection, donor’s specific antibodies, gastroesophageal reflux, and pulmonary infections (due to cytomegalovirus, Pseudomonas aeruginosa, Staphylococcus aureus, Aspergillus) are associated with the development of CLAD. We are therefore conducting studies obtaining longitudinal samples on subjects undergoing lung transplantation to identify lower airway microbiota signatures associated with changes in immune phenotype and development of CLAD.