Publications by authors named "Michael V Lasker"

Background: The proper approach to repair of complex abdominal wall hernia in contaminated and dirty surgical fields is unknown. Identification of a surgical approach limiting the number of operative procedures, post-operative complications, and financial burden is needed. We hypothesized that single-stage abdominal wall reconstruction using poly-4-hydroxybutyrate resorbable mesh would result in low incidence of post-operative surgical site occurrence and a low incidence of hernia recurrence in Centers for Disease Control class III and IV wounds.

View Article and Find Full Text PDF

Glucocorticoids are indispensable therapeutic agents in diseases of inflammation, but their effectiveness in treating advanced septic shock has been inconsistent. Our understanding of the mechanisms causing this variability to steroid therapy remains limited. Previous studies in our laboratory have implicated human glucocorticoid receptor (hGR) polymorphisms as one of the likely reasons for this variability.

View Article and Find Full Text PDF

TLRs are crucial sensors of microbial infection. Maintaining structural integrity of TLR signaling components is essential for subsequent immunological protection. Alterations to the structure of these signaling molecules are often associated with profound clinical outcomes and susceptibility to various infectious diseases.

View Article and Find Full Text PDF

Interleukin-1 receptor-associated kinase-4 (IRAK-4) is an essential component of innate immunity in mice and humans. IRAK-4 is a bipartite protein composed of a death domain (DD) that mediates molecular recognition, and a catalytic kinase domain. Structure determination of the proteolytically stable, soluble IRAK-4 DD was hampered by poor diffraction quality.

View Article and Find Full Text PDF

IL-1R-associated kinase (IRAK) 4 is an essential component of innate immunity. IRAK-4 deficiency in mice and humans results in severe impairment of IL-1 and TLR signaling. We have solved the crystal structure for the death domain of Mus musculus IRAK-4 to 1.

View Article and Find Full Text PDF

This study aims to investigate functionally similar proteins based on their capacity to remain bound to ATP under stringent resolving conditions. Using two-dimensional gel electrophoresis and capillary liquid chromatography on-line mass spectrometry, we have identified several mammalian and E. coli proteins that appear to covalently bind ATP.

View Article and Find Full Text PDF

Whereas phosphoesters of serine, threonine, and tyrosine are present in great abundance in mammalian cells, only limited information is available for other amino acids modified by a phosphate group. Phosphohistidine in proteins has been discovered in mammalian cells, but no enzyme with histidine kinase activity has been reported to date. The present study demonstrates for the first time the histidine kinase activity of a mammalian protein.

View Article and Find Full Text PDF

The 90-kDa heat shock family (HSP90) of protein and two-component histidine kinases, although quite distinct at the primary amino acid sequence level, share a common structural ATP-binding domain known as the Bergerat fold. The Bergerat fold is important for the ATPase activity and associated chaperone function of HSP90. Two-component histidine kinases occur in bacteria, yeast, and plants but have yet to be identified in mammalian cells.

View Article and Find Full Text PDF