Research
Pathobiology of Renal Epithelial Injury
This aspect of our investigation has been directed towards a detailed
analysis and understanding of the complex morphologic features, physiologic
mechanisms and metabolic processes which are involved in the recovery
from acute renal failure. The present investigations are designed to
determine the cellular and molecular basis of the morphologic and physiologic
preservation that accompanies recovery from renal epithelial injury
and specifically to investigate the role of adenine nucleotide metabolism
in the initiation of renal cellular injury, activation of the stress
response and recovery. Studies to investigate the integrity of cell
plasma membrane structure and function and how it is affected by ATP
depletion are being conducted to determine the signaling mechanisms
that provide a cross link between the cytoskeletal alterations, cellular
nucleotides, induction of the stress response and the loss of membrane
integrity. The contribution of the stress response via the induction
of heat shock proteins is being studied to determine how these proteins
may be involved in cytoprotection by recycling of proteins displaced
from their correct membrane domains and how polymorphisms of the gene
affect their expression.
Function and Structure of Transporting Epithelia
The structural and functional characteristics of various transporting
epithelia are being studied in a variety of normal, adaptive, and pathologic
states and it is intended to correlate structure and function at the
cellular level. Ultrastructural and confocal microscopy techniques are
being used to study adaptive changes in the transporting epithelium.
A second area of investigation concentrates on the use of monoclonal
antibodies and molecular probes to membrane associated transport proteins.
These techniques have been used to assess some aspects of the functional
characteristics of NaK-ATPase as well as studying cellular biosynthesis,
assembly, and polar insertion into the plasma membrane. In addition,
tissues such as colon, liver, heart and brain are also being studied
relative to the distribution of isoforms of this enzyme and its relationship
to specific transport functions. Additional studies are being
directed at the isolation of other transport proteins to study their
distribution and function. These include the potassium-proton pump of
the colon, CFTR, the polycystins and vacuolar H-ATPase. In addition,
studies are underway to investigatethe interactions of transport proteins
with adaptor molecules and cytoskeletal elements and the role of these
interactions in the development
and maintenance of cell polarity as well as in cyst formation.
Pathology of Progressive Glomerular Sclerosis
This area of investigation is designed to examine the factors which
are involved in the initiation and progression of renal scarring. Mesangial
cells are grown on different defined matrices and are examined for the
effect of growth factors on the expression of the phenotypic features,
such as their biosynthetic profiles of matrix and cytoskeletal proteins
including laminin, fibronectin and collagen types I, III, IV and
V, myosin as well as neutral proteases, and cytokines under diabetic conditions. The
intracellular signaling mechanisms which are disturbed under these conditions
are also being investigated
-top-