The breakthrough of CFTR modulator therapies to treat CF patients has greatly improved the trajectory of lung disease. However, lung hyper-inflammation is not well controlled by CFTR modulator therapy. Given the substantial role of hyper-inflammation in the pathogenesis of CF-related lung disease, there is a need for aggressive treatments that will prevent the progressive lung tissue deterioration in CF patients.
Our group has ascertained that CF-affected monocyte/macrophages (MΦ) are dysfunctional, contributing to lung hyper-inflammation. We published this pioneering research in the American Journal of Respiratory Cell and Molecular Biology in 2009. Based on these results, we are now investigating the molecular mechanisms associated with CF MΦ dysfunctions.
One of the main focuses of our group is to understand how mucosal homeostasis develops in infants and young children, particularly as it relates to development and maintenance of adaptive immunity. Using a combination of single cell techniques, we are studying intestinal immunity of fetal, premature and term infants and pediatric subjects. Furthermore, we are interested in determining how mucosal homeostasis becomes dysregulated in intestinal diseases such as necrotizing enterocolitis and inflammatory bowel disease.
Our lab’s focus is on cellular immunology and how individual variations in immunity contribute to disease susceptibility. Our work is notable for use of primary human immune cells and novel technology including multiparameter phenotyping and high dimensional transcriptional and proteomic assays. I direct the CyTOF facility at Yale and published the first reports using this multi-dimensional technique for studies of primary tissue including skin and airway sputum. We are studying immune mechanisms in aging, in infections such as West Nile virus and COVID-19, and recently began studies of sickle cell disease. We participate in several multi-institutional studies including COVID-19 translational studies and asthma clinical trials. These investigations employ in-depth computational analysis to demonstrate immune related mechanisms and illuminate potential avenues for therapeutic interventions.
Our group is conducting research across multiple domains including Human Genetics, Biological Psychiatry, Evolutionary Biology, Statistical Genetics, and Computational Biology. The overarching goal of our efforts is to understand the link between the human genome and phenome from multiple perspectives. We are part of the Yale Psychiatry Division of Human Genetics, which is located in the Veterans Affairs Connecticut Healthcare Center, West Haven, Connecticut. Our ongoing studies are currently funded by the National Institute on Drug Abuse, the National Institute on Deafness and Other Communication Disorder, the National Institute on Mental Health, the Department of the Veterans Affairs, the Marie Skłodowska-Curie Actions, and One Mind. Additionally, we are also involved in large collaborative projects including the Psychiatric Genomics Consortium, the Million Veteran Program, and COVID-19 Host Genetic Initiative.