研究

肺分区, 急救护理, and 睡眠医学 is involved in many clinical and translational research projects. Active areas of research include clinical trials of biologics in obstructive lung disease, COPD和IPF的多组学研究, and observational studies in critical care.

Gene expression signatures of extrapulmonary sarcoidosis 

Previous research has identified selected genes, particularly from a part of the cell machinery called the mitochondria, that have been associated with sarcoidosis affecting many organs. 然而, there have not been any studies that investigate which genes may be related to sarcoidosis affecting many organs across the entire human genome using state-of-the-art RNA sequencing technology. Our project will compare the expression of genes in the blood of patients with sarcoidosis in many organs to patients with sarcoidosis only in the lungs to identify which genes are different between the two groups.

 

Genetic and genomic 弹性 to COPD

Chronic obstructive pulmonary disease is an important cause of respiratory morbidity and mortality. While there are many strong risk factors for COPD (e.g., 年龄与吸烟), there is considerable variability in disease that is unexplained by these factors. There has been significant progress in our understanding of the genetic and biologic bases of COPD, which has led to improved quantification of individual risk for disease. Yet, despite being at considerable levels of risk, some individuals do not develop disease. 研究 弹性 to COPD remains almost entirely unexplored, despite the considerable public health ramifications of identifying factors that ameliorate risk. 弹性, in the context of genetics and biology, represents the capacity to withstand the risk of disease. As the reliability of risk-prediction in COPD increases, so too does the prospect of investigating 弹性 to COPD. 弹性, in the context of genetics and biology, represents the capacity to withstand the risk of disease. As the reliability of risk-prediction in COPD increases, so too does the prospect of investigating 弹性 to COPD. Understanding how some individuals with high genetic risk and/or high burden of environmental exposure (e.g., heavy cigarette smokers with normal lung function) avoid developing COPD may uncover novel opportunities to prevent development, 早期干预, and treat established and advanced disease. One approach to identifying factors contributing to 弹性 has been successfully demonstrated in non-pulmonary diseases, including schizophrenia and Alzheimer’s disease, in the form of validated polygenic 弹性 分数. We hypothesize that polygenic and transcriptional elements contribute to 弹性 to COPD, and identification of resilient phenotypes will significantly advance our understanding of observed heterogeneity in the genomic and environmental risk of COPD, which can be used to identify novel phenotypes of 弹性.

 

理解 MUC5B expression in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis is a progressive and often fatal lung disease characterized by destruction of lung parenchyma and accumulation of dense fibrotic tissue. There are a number of genetic factors that have been associated with the risk of development of IPF. The mucin 5B 启动子变体 rs35705950 has repeatedly been shown to be the largest contributor to the genetic susceptibility of IPF. The putative mechanism by which the variant increases risk of disease is thought to be its role as an expression quantitative trait locus, 这样的存在 MUC5B 启动子变体 leads to increased expression of MUC5B. 然而,增加 MUC5B expression has been demonstrated in IPF independent of the MUC5B 启动子变体. Therefore, there is substantial variability in MUC5B expression in IPF that remains unexplained. Previous studies have used lung tissue gene-expression data to identify distinct endotypes of IPF. One such endeavor identified an endotype of IPF, enriched for cilium-associated genes, which was found to have higher expression of MUC5B. While several other transcriptomic characteristics were associated with the cilium endotype of IPF, 协会 MUC5B 启动子变体 with the endotype and any differential effects of the variant as an eQTL between endotypes have not been investigated. Given the large observed effect of the MUC5B 启动子变体 on the genetic risk of IPF, accounting for approximately 30% of the risk of developing IPF, further insight into its role as an eQTL may advance our understanding of the mechanism of the variant in the pathogenesis of IPF. 我们的项目将测试 假设 那(1) MUC5B 启动子变体 is an endotype-dependent eQTL and that (2) there are other genetic variants and gene regulatory elements associated with the eQTL effect on MUC5B.