Publication

Background: Chronic bacterial infections pose a significant problem for individuals living with cystic fibrosis (CF) because of their correlation with lung function decline. Although there are several antibiotic therapies to treat and manage infections caused by Pseudomonas aeruginosa and other species, there are limited interventions for nontuberculous mycobacterium (NTM) infections, which affect approximately 10% of CF patients. Although clearance of NTM infection slows the rate of lung function decline, culture conversion and cure rates remain low despite intensive treatment regimens.

Background: Culture-independent microbiota analysis has permitted comprehensive investigation of bacterial diversity in cystic fibrosis (CF) lung infections and is being increasingly used to examine fungal communities. The prevalence and clinical impact of fungi in CF is relatively poorly understood, with studies largely focused on adults. We investigated fungal diversity in children with CF aged 1 to 18 years using bronchoalveolar lavage (BAL) and induced-sputum (IS) samples to capture multiple niches within the lung.

Background: SARS-CoV-2 (SARS2) continues to place an unprecedented burden on global health. SARS2 is a respiratory virus that, in a minority of patients, causes severe pneumonia, which portends a poor prognosis. There is emerging evidence of long-term respiratory sequelae secondary to SARS2, including impaired lung function and persistent lung imaging abnormalities. CF patients often face prolonged morbidity and exacerbation of lung disease as a consequence of respiratory virus infection.

Background: Pseudomonas aeruginosa, the predominant pathogen in chronic lung infection of adults with cystic fibrosis (CF), possesses a number of mechanisms that contribute to antimicrobial resistance (AMR). Even aggressive antibiotic treatment is unable to effectively clear chronic P. aeruginosa, which may partially be due to the rapid diversification displayed by P. aeruginosa during long-term CF infection, but our knowledge of the role of population heterogeneity on AMR is limited, because prior studies have undersampled P. aeruginosa isolates in CF lungs.

Background: Inhaled antibiotics control chronic airway infection and maintain respiratory health in cystic fibrosis (CF). Given variation in patient responses to inhaled antibiotics, the ability to identify distinct responder phenotypes would facilitate delivery of personalized care. Previously a 10- gene panel was identified, measured directly from blood leukocytes, that predicted response to intravenous antibiotic treatment during pulmonary exacerbations.

Background: Analysis of reporter gene expression by fluorescent microscopy is a routine way to determine gene transfer efficiency in tissues. Quantifying transduction efficiency within tissues can be complicated and laborious to perform manually. There is a need for development of new semi- and fully automatic processing tools for analysis of microscopy images.

Background: In CF, impaired nitric oxide (NO) production may contribute to impaired host antimicrobial defense, chronic airway infection, and compromised pulmonary function. L-arginine (Arg) is a required substrate of NO synthases for production of NO. Depletion of Arg by arginase, an abundant enzyme expressed and secreted into airways by neutrophils, contributes to NO deficiency. Clinical studies in CF patients have shown that administration of inhaled Arg improved fractional exhaled NO (FeNO) and trended toward improvement in FEV1.

Background: Defective CFTR causes dehydration and acidification of the airways, which leads to chronic bacterial infection, inflammation, and frequent exacerbations. Repeated cycles of infection and inflammation result in a downward spiral of injury and remodeling that ultimately leads to bronchiectasis and respiratory failure. Therefore, management of airway inflammation is a vital aspect of CF treatment, but other than ibuprofen, there are no currently approved antiinflammatory drugs to treat CF patients.

In the ovarian follicle, the Theca Cells (TCs) have two main functions: preserving morphological integrity and, importantly, secreting steroid androgen hormones. TCs express the essential enzyme 17α-hydroxylase/17,20-desmolase (CYP17), which permits the conversion of pregnenolone and progesterone into androgens. Dysregulation of CYP17 enzyme activity due to an intrinsic ovarian defect is hypothesized to be a cause of hyperandrogenism in women.

Chimeric antigen receptor (CAR) T cells have largely been successful in treating hematological malignancies in the clinic but have not been as effective in treating solid tumors, in part, owing to poor access and the immunosuppressive tumor microenvironment. In addition, CAR-T therapy can cause potentially life-threatening side effects, including cytokine release syndrome and neurotoxicity. Current preclinical testing of CAR-T therapy efficacy is typically performed in mouse tumor models, which often fails to predict toxicity.