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Bile acids are potentially toxic compounds and their levels of hepatic production, uptake and export are tightly regulated by many inputs, including circadian rhythm. We tested the impact of disrupting the peripheral circadian clock on integral steps of bile acid homeostasis.
Both restricted feeding, which phase shifts peripheral clocks, and geneti...
Two members of the angiopoietin-like family of proteins, ANGPTL3 and ANGPTL4, have been shown to play important roles in modulating lipoprotein metabolism in the body. Both proteins were found to suppress lipoprotein lipase (LPL) activity in vitro as well as in vivo. However, their mechanisms of inhibition remained poorly understood. Using enzyme k...
Gluten is one of the most ubiquitous ingredients in the human diet. The unique physicochemical properties of this biomaterial are the result of its primary structure (rich in Pro and Gln residues), secondary structure (abundance of non-hydrogen bond dependent polyproline II helices), and tertiary and quarternary structures (extensive intra- and int...
Dietary gluten proteins from wheat, rye, and barley are the primary triggers for the immuno-pathogenesis of Celiac Sprue, a widespread immune disease of the small intestine. Recent molecular and structural analyses of representative gluten proteins, most notably alpha- and gamma-gliadin proteins from wheat, have improved our understanding of these...
Prolyl endopeptidases (PEPs) are a unique class of serine proteases with considerable therapeutic potential for the treatment of celiac sprue. The crystal structures of two didomain PEPs have been solved in alternative configurations, thereby providing insights into the mode of action of these enzymes. The structure of the Sphingomonas capsulata PE...
Prolyl endopeptidases have potential for treating coeliac sprue, a disease of the intestine caused by proteolytically resistant peptides from proline-rich prolamins of wheat, barley and rye. We compared the properties of three similar bacterial prolyl endopeptidases, including the known enzymes from Flavobacterium meningosepticum (FM) and Sphingomo...
Two recently identified immunodominant epitopes from alpha-gliadin account for most of the stimulatory activity of dietary gluten on intestinal and peripheral T lymphocytes in patients with celiac sprue. The proteolytic kinetics of peptides containing these epitopes were analyzed in vitro using soluble proteases from bovine and porcine pancreas and...
Celiac Sprue, a widely prevalent autoimmune disease of the small intestine, is induced in genetically susceptible individuals
by exposure to dietary gluten. A 33-mer peptide was identified that has several characteristics suggesting it is the primary
initiator of the inflammatory response to gluten in Celiac Sprue patients. In vitro and in vivo stu...
Submitted to the Department of Chemical Engineering. Copyright by the author. Thesis (Ph. D.)--Stanford University, 2005.