530 45th St.
8118 Rangos Research Center
Pittsburgh, Pennsylvania 15201
My current research interests can be broadly classified into two main avenues of investigation. First, to elucidate the signaling role played by cilia during heart/vascular embryonic development, and second, to determine the physiological relationship between nitric oxide signaling and motile cilia function within the adult respiratory epithelium.
The heart is a highly asymmetric organ and this asymmetry is crucial for its normal function. The left side of the heart pumps blood under high pressure to the whole body, while the right side pumps blood at a lower pressure to the lungs. During development the heart starts as a simple tube that elongates and twists up upon itself to form a loop like structure. Problems with normal asymmetric looping result in a number of developmental diseases including early embryonic lethality and congenital heart disease. We have identified a number of proteins crucial for heart looping and subsequent heart development that localize to the cilia. We are currently investigating the mechanism(s) by which these proteins and the cilia itself modulates normal heart development.
Chronic airway disease is one of the most prevalent types of chronic disease worldwide and includes diseases such as cystic fibrosis, asthma, chronic bronchitis, and primary ciliary dyskinesia (PCD), all of which are commonly characterized by mucociliary dysfunction. However, even in light of the critical physiological importance of normal mucociliary activity, the mechanisms controlling mucociliary function in respiratory epithelia are still very poorly understood. PCD is a rare disorder, usually inherited as an autosomal recessive trait, characterized by a defect in normal respiratory cilia motility causing defective mucociliary clearance. One surprising finding was the significant correlation between PCD and low exhaled nitric oxide (NO). The correlation between PCD and exhaled NO is such that the measurement of NO is becoming a commonly utilized diagnostic approach for evaluating the presence of PCD. The reason why NO production is linked to motile cilia function is unknown and has received little attention, and it’s this relationship that we are currently investigating. We propose that a direct link exists between respiratory cilia and NO activity, and that this mechanism plays an important physiological function in regulating normal mucociliary clearance in the respiratory system. We predict that elucidating the role played by NO synthesis and release from the respiratory epithelia, specifically in relation to cilia motility, may lead to important treatment options for different chronic airway diseases.
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