Janssen-Heininger Lab Research
Research: To unravel the molecular basis of diverse pulmonary diseases that are characterized by chronic fibrotic remodeling by emphasizing the biology of epithelial cells and redox-dependent processes.
Education: To provide an exciting research environment and extensive mentoring to all laboratory members to enable each of them to be maximally successful in the arena of biomedical sciences in diverse capacities.
Product development: We have a number of patented small molecules and are passionate to advance these as potential drugs to treat fibrotic lung diseases. Laboratory members have the opportunities to work with a number of companies in order to acquire expertise in drug development.
Values: We work as a close-knit team, and together strive to advance knowledge and to have a positive impact on the lives of people with chronic lung disease. We are highly dedicated group of professionals who work hard, and know how to have fun.
Overview of current areas of research and approaches
Epithelial cells, metabolic reconfiguration, andchronic inflammation in obese asthma:
We are interested in the role of airway epithelium-derived signals in the control of inflammation and remodeling. Numerous studies have demonstrated the critical role of epithelium in innate defense to a diversity of inhaled agents and subsequent triggering of inflammation. We are examining a member of the family of kinases in the Nuclear Factor kappa B (NF-kB) family and are determining whether its ability to change metabolism plays a role in asthma, notably obese asthma. We are unraveling the molecular details whereby changes in metabolism drive chronic inflammatory responses.
Epithelial cell plasticity and lung fibrosis:
Epithelial cells can be activated and transdifferentiate into cells with unique effector functions. These include mucus metaplasia, and mesenchymal activation, the latter important in wound healing. We have identified that the stress responsive c-Jun-N-terminal kinase (JNK1) plays a causal role in the regulation of epithelial cell plasticity. We are unraveling the molecular signals whereby JNK1 exerts this pathological role and with a company are testing JNK1 specific inhibitors as targets for airway remodeling.
We have discovered that S-glutathionylation, the process wherein glutathione becomes covalently attached to reactive protein cysteines, is critical in disruption epithelial cell function, and contributes to chronic inflammation and lung remodeling. We are addressing the enzymes (glutaredoxin and glutathione S-transferases) that control this process. The goal is to limit specific S-glutathionylation targets via the development of clinically relevant approaches to attenuate chronic inflammation and remodeling. We are also investigating the structural requirements that enable S-glutathionylation, and the oxidative steps preceding it.
Technologies and functioning of the laboratory:
We employ a diversity of state-of-the-art cell and molecular biological and biochemical approaches. Significant emphasis of the laboratory is centered on gene manipulation, 3-dimensional cultures of primary cells, and scaffolded decellularized lungs in order to maximize the validity of cell-based systems. We utilize an array of protein thiol redox probes and have developed patented approaches to visualize cysteine oxidations in intact cells and tissues.
In collaboration with clinical investigators we are intensely investigating the extent to which protein thiol redox changes can be developed as biomarkers. The intellectual and technical expertise in the laboratory, provided by diversely skilled postdoctoral fellows, research associates, and visiting scholars, coupled with the direct proximity of clinical invstigators in the Redox Biology and Pathology program, and the Vermont Lung Center provide a rich and stimulating environment for students and fellows. Laboratory members have the opportunity to travel to one international conference annually, and to attend weekly Redox Biology and Pathology, Vermont Lung Center and Immunobiology seminar series.