Dr. Lamb is interested in how LRRC8 family anion channels support and regulate reactive oxygen species-dependent cytokine signaling in vascular smooth muscle cells. Disrupting the expression or function of these channels reduces extracellular production of superoxide anion by NADPH oxidase 1 (Nox1). This superoxide is required for signaling by molecules such as TNFα, IL-1β and bacterial endotoxin that promote inflammation. Movement of superoxide into cells via LRRC8 channels can also promote oxidative stress and cell injury. The Lamb lab is working to understand if inhibition of these channels can provide protection from both acute (sepsis), and chronic (hypertension, diabetes, atherosclerosis) vascular dysfunction.

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Research in the Kon lab has focused on exploring connections between chronic kidney disease (CKD) and cardiovascular disease (CVD) especially on mechanisms underlying CKD-associated dysfunction in macrophage lipid handling and inflammatory function. This field has gained urgency because of strong epidemiologic evidence that individuals with any degree of renal dysfunction are at a tremendously increased risk for developing CVD. Our studies have established that even in the absence of long-standing CKD and concomitant risk factors, CKD in childhood causes specific lipoprotein abnormalities linked to maintenance of normal vascular function, including inflammatory responses in macrophages and production of adhesion molecules by endothelial cells. In more recent studies, we show that that kidneys are involved in lipoprotein homeostasis and that kidney disease modifies lipoprotein structure, composition, and function which in turn modulate cells in the renal parenchyma. We are especially interested in the role of renal lymphatic vessels which transport lipoproteins out of the interstitial compartment, and we propose are key mediators of the renal response to injury. The laboratory utilizes molecular approach, cellular physiology techniques, and genetically modified mouse models as well as rat models of renal injury to understand how lymphatic vessels affect kidney disease.

>> View Dr. Kon's publications on PubMed.