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Matrix Biology

BASIC SCIENCE

acute kidney injurychronic kidney diseasediabetic nephropathykidney development,  hypertensionintegrin biology,  growth factors, eicosanoid biologygene deliveryendothelial cell biologybioartificial kidney


                                            Matrix Biology

 

Research in the VCKD is leading to new insights and treatment options for kidney fibrosis in progressive kidney disease, including diabetic nephropathy.

Director

 

Members

The Bhave Lab is interested in the assembly and function of basement membranes and extracellular matrix in kidney disease. By studying matrix biochemistry at a fundamental level, we hope to gain insight into renal glomerular and tubulointerstitial fibrosis which represents the common final pathway to injury in nearly all kidney diseases. Our group utilizes cell culture systems, molecular biology, biochemistry, mass spectrometry, and mouse genetics to answer questions of interest.

The Fissell Lab is interested in biomimetic filters that reproduce the filtration characterisitics of the human glomerulus. The Fissell lab has developed a novel model of the glomerular filtration barrier where the fluid flow of glomerular filtration from inside the capillary lumen to Bowmans space compresses the glomerular basement membrane against the podocyte cell bodies and foot processes.  The gel filtration properties of extracellular matrix components and how they are dynamically modulated are dictated by basement membrane assembly and crosslinking.  Present research is focused on identifying physiologically relevant in vitro models of gel filtration and gel compression and in vivo 2-photon confocal imaging of the glomerular capillary wall.

The Fogo laboratory studies mechanisms of progression of kidney disease and potential regression of glomerulosclerosis. The laboratory focuses on key interactions of glomerular cells, and the  effects of the renin angiotensin system and plasminogen activator inhibitor-1 (PAI-1) on these interactions, using genetically engineered mice and cell culture.

The Gewin lab studies how growth factors such as TGF-beta alter the production of extracellular matrix after renal injury. We are interested in the cell-specific effects of TGF-beta and use mouse models with cell-specific genetic alterations and cell culture techniques to better understand the differential effects of TGF-beta on epithelial and mesenchymal production of matrix.

The Hudson lab focuses on deciphering the molecular structure of the kidney filtration barrier in health and disease. Our goal is to  determine the molecular basis for kidney failure in patients with diabetes, Alport syndrome and Goodpasture’s disease  and  to design  therapy to protect against the progression to end stage renal disease. In particular, we focus on how altered assembly of collagen IV, a key component of the kidney filtration barrier, cause kidney failure.  Recently, our team discovered a new chemical bond that reinforces the structural integrity of the collagen scaffold and shown it to be a primordial event for tissue evolution. We have identified a drug candidate (pyridorin) for the treatment of diabetes renal disease, which was approved by the FDA and is currently under Phase III clinical trial.

The Pozzi lab studies how integrins, transmembrane receptors for extracellular matrix, control matrix homeostasis in healthy and diseased kidneys.  The lab found that integrin α1β1, a major collagen IV receptor, plays a protective role in the course of renal injury by negatively regulating collagen production. In contrast, integrin α2β1, a major collagen I receptor, contributes to renal injury by enhancing collagen production. Using genetically engineered mice together with in vitro techniques, the Pozzi lab is investigating the molecular, cellular, and biochemical mechanisms whereby these two integrins differentially regulate matrix homeostasis.

The Vanacore lab uses state of the art proteomic methodologies to investigate abnormalities in collagen IV synthesis and post-translational modification in diabetic nephropathy, with an aim to understanding the underlying mechanisms of progressive glomerulopathy in diabetic nephropathy.

The Zent lab studies basic mechanisms of integrin function using the kidney as a model organ. The main focus of the lab is to define the mechanisms whereby integrins regulate cell function and signaling; define how integrin cytoplasmic tails interact with cytoplasmic proteins to regulate cell function and define the structural determinants of specificity of integrin-dependent signaling. The major techniques used to answer these questions include the making and characterization of transgenic mice, cell biology and biochemical techniques as well as structural methodologies including 3-dimensional nuclear magnetic resonance.