My long-term interest is mathematical modeling of solute and water
transport across epithelia, specifically the renal epithelia. For
a number of years attention was restricted to proximal tubule physiology,
but the current focus is on a mathematical model of the mammalian distal
nephron. The model represents Na, K, and acid/base transport under
normal and pathological conditions, and predicts their renal excretion,
given distal delivery. An important aspect of this work is simulation
of distal nephron dysfunction. In experimental models, specific segmental
transport defects have been identified. The model can be used to assess
the extent to which known defects can account for observed solute excretion
patterns. Conversely, simulations of clinical tests of distal nephron
function can be used to evaluate their accuracy in defining a specific
transport defect.
A second aspect of this project is investigation into the theory of cell
volume regulation during fluctuations of net transport. Critical to epithelial
cell viability is homeostasis of cell volume and composition during changes
in transcellular transport. Mathematical models of epithelia may be
extended with the inclusion of functional dependence of membrane transport
coefficients on cell variables (e.g. volume, solute concentrations, or
electrical potential). This effort entails a systematic examination of
homeostasis in epithelial models, and provides a framework for
identification of candidate control parameters.
|
