Brian P. Hackett, M.D., Ph.D.

DEPARTMENT OF Pediatrics
Keywords: cilia, lung, pulmonary epithelium, left-right axis, development, heterotaxia

Our laboratory is interested in the molecular and cellular mechanisms that regulate the formation of cilia in the respiratory epithelium. We are also interested in the mechanisms that result in the loss of cilia in response to injury or infection and subsequent recovery of cilia. Our laboratory has identified a transcription factor, Foxj1, that is essential for the formation of ciliated cells through regulation of the apical cytoskeleton. Current investigations in the laboratory are examining the cellular and molecular biology of basal body linkage to the apical cytoskeleton. Additionally, we are examining the role of cytoskeletal stability in the loss of cilia associated with pulmonary disease.

Cilia in the embryonic node play an essential role in left-right axis patterning by establishing an asymmetric pattern of gene expression during development. Patterning along the left-right body axis results in a conserved, non-random asymmetry of the internal viscera of vertebrates. Errors in left-right axis patterning can result in congenital malformations, termed heterotaxia, that result in significant morbidity and mortality. The transcription factor Foxj1 is essential for normal, non-random left-right axis pattern formation. Foxj1 is expressed in the embryonic node and regulates asymmetric left-right gene expression in the early embryo. Current studies in our laboratory are examining the molecular and cellular mechanisms involved in the regulation of left-right axis gene expression by Foxj1.