Dr. Mikacenic’s lab focuses on identifying the underlying mechanisms of certain lung diseases. The current focus is on Acute Respiratory Distress Syndrome (ARDS) that occurs in response to critical illness and in interstitial lung diseases (ILD). ILD is present in some patients with autoimmune disease such as rheumatoid arthritis, scleroderma and dermatomyositis. The translational immunology lab studies the innate and adaptive immune responses in the lungs with these conditions. The main goals are to identify novel pathways for treatments and to identify biomarkers that predict disease onset and severity.
T cell polarization & ARDS
In murine models of lung injury, regulatory T cells play an important role in the resolution of pathologic inflammation, while inflammatory T cell subsets may promote injury. The laboratory is currently studying T cell polarization in the lung in the context of ARDS, with a particular focus on IL-17 production.
Alveolar Macrophage Phenotype & Function
Dr. Mikacenic’s lab is studying alveolar macrophage phenotype and function in patients with ARDS. In ARDS, Dr. Mikacenic found that there are increased populations of recruited monocytes and that alveolar macrophages have lower expression of PD-L1. Studies are ongoing to understand how these differences may prohibit resolution of lung inflammation in ARDS.
Genetic Variants Associated with ARDS & Organ Failure in Critical Illness
Dr. Mikacenic has identified common genetic variants that are associated with lung injury and other organ dysfunction, like acute kidney injury, in patients who are critically ill with sepsis. Particular genes of interest include TLR1 and FAS (CD95). These TLR1 variants have been shown to be associated with hyperactivation of innate immune responses and also to impair the ability of effector T cells to be suppressed by Treg. Genotype-phenotype studies are ongoing in collaboration with investigators at the University of Washington.
Biomarkers of Interstitial Lung Disease
Dr. Mikacenic has a clinical practice in which she sees patients with interstitial lung disease. The lab is focused on identifying biomarkers that identify patients with autoimmune disease who are at risk to develop lung disease. Another focus is to understand biomarkers of disease progression in Sarcoidosis.