MOLECULAR MECHANISMS OF RENAL INFLAMMATION AND INJURY

Inflammation and injury to the kidney is usually a product of complex
biochemical events. These events initiate and provide dynamic conduits
for the calamitous progression towards end-stage kidney disease in
humans. We believe that a better comprehension of the proximal
mechanisms underlying these interlocking and destructive processes may
offer new insights leading to the formation of rational strategies for
improved treatment. The major theme of our Renal Center focuses,
therefore, on the engagement of fundamental molecular mechanisms which
detrimentally facilitate the development of parenchymal Injury and Its
extended consequences to target structures and somatic cells along the
nephron. Our research will examine several different categories of
interactions in a series of new and provocative studies. These projects
will collectively bridge the disciplines of genetics and biochemistry
with basic pathophysiology in order to better evaluate events preceding
the aberrant structural change of renal tissue. This grant will support
nine academic scientists located physically in one comprehensive research
facility consisting of thirty-eight individual experimental work stations
surrounding a common core area containing large equipment, and providing
space for nucleic acid sequencing and tissue culture. Our Renal Center
will be composed initially of four major research projects and three core
units: Project 1 will use molecular and cellular techniques to determine
the mechanisms by which glomerular injury produces subsequent
tubulointerstitial inflammation; Project 2 will focus on the molecular
determinants and biologic consequences of nuclear localization of
anti-DNA antibodies in renal cells; Project 3 will investigate the
molecular and biochemical factors which induce renal cell growth and
hypertrophy in diabetes mellitus; and Project 4 will study the molecular
mechanisms by which regulatory T cells mediate a specific and highly
targeted downregulation of autoimmune renal injury. Core units for
tissue cell culture, for oligonucleotide synthesis and nucleic acid
sequencing, and for project administration will be established as part of
the supportive infrastructure. Our Renal Center will also serve as a
regional resource for the tertiary care of renal patients with various
forms of inflammatory kidney damage.