Mechanisms of epithelial transport in health and disease

My research focuses on the mechanisms of epithelial solute transport, its regulation by extracellular and the intracellular signals, and the pathological consequences of transport failure. 

Currently, we have two main research programs involving:

1) Cystic fibrosis airway disease pathobiology:

Cystic fibrosis (CF) is an autosomal recessive condition caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. The main objective of my research program is to study the link between the mutation of CFTR and the failure in CF patients of the innate defence mechanisms that normally protects airways from infection. Normal airways are protected from inhaled ‘insults’ by a complex immune defense system that includes mucus containing antimicrobial factor that traps and inactivates bacteria favoring clearance from the airways. We examining:

  1. Response of airway submucosal glands to proinflamatory cytokines
  2. Stimulation of mucus secretion by bacteria inhalation by swine in vivo  using synchrotron light

2) Molecular and cellular mechanisms of epithelial transport:

The fundamental function of transporting epithelia is to generate the electrochemical gradients resulting in movement of molecules. This is achieved by the asymmetrical distributions of transport systems (channels, ATPases, cotransporters and exchangers) in the apical and basolateral membranes of polarized epithelial cells. ATPases generate electrochemical gradients in active transport which are exploited to produce unidirectional movement of solutes. Our lab examines the molecular and cellular mechanisms that allow these transport machinery to work in renal tubules of the insect models Drosophila melanogaster and Rhodnius prolixus.

The role of intracellular Ca2+ in the cross-talk between apical and basolateral transporters in Rhodnius prolixus Malpighian tubules

Epithelial solute transport

Of all the ways in which animal cells are woven together into multicellular tissues, the epithelial arrangement is perhaps the most fascinating and fundamentally important. Epithelial sheets of cells line all external and internal surfaces in the body, and are specialized for the selective secretion and absorption of ions and organic molecules. This leads to the creation of sheltered compartments with controlled internal environments where specialized functions are performed by differentiated cells.

The laws of thermodynamic govern the direction and rate of movement of solutes across epithelial cells, i.e. down the electrochemical gradient for any molecule. The fundamental function of transporting epithelia is to generate the electrochemical gradients that will force movement of molecules in the desired direction. This is achieved by the asymmetrical distributions of transport systems (channels, ATPases, cotransporters and exchangers) in the apical and basolateral membranes of polarized epithelial cells. Primary active transport by ATPases generates electrochemical gradients that are exploited by membranes with selective permeability to produce unidirectional movement of solutes that would otherwise be thermodynamically unfavorable.

Funding