The Department of Microbiology & Immunology Research in Progress Seminar Series: Tynetta C. Fletcher
8/21/2008
9:30 am
- 10:30 am
Contact:
Location:
Medical Center North (MCN) A5305
Category:
Open to the Public
Tynetta C. Fletcher, Graduate Student
Meharry Medical College
From the laboratory of Dr. Jacek Hawiger
"The Expression, Turnover, and Reconstitution of SOCS-3 During Endotoxin-Induced Septic Shock"
Septic Shock Syndrome, an acute systemic inflammatory disorder caused by Gram- negative and Gram-positive bacteria, is characterized by unregulated cytokine production, multi-organ damage and vascular collapse. By using a model of endotoxic lipopolysaccharide (LPS)-induced Septic Shock, we were able to counteract the lethal effects of LPS with a novel intracellular protein therapy (IPT) based on a cell-penetrating form of Suppressor of Cytokine Signaling-3 (CP-SOCS3). SOCS3 is a known physiologic inhibitor of the JAK/STAT pathway as well as LPS-activated IRAK1/TRAF6 and TRIF/TRAF3 pathways. An unanticipated benefit of using CP-SOCS3 in vivo is its persistence in blood leukocytes/lymphocytes and spleen cells, suggesting different intracellular kinetics for this bioengineered protein. Comparative analysis of endogenous and cell-penetrating forms of SOCS3 turnover allows us to elucidate the mechanism of its persistence and to develop CP-SOCS3 variants that would offer more effective IPT against LPS-induced lethal shock.
Meharry Medical College
From the laboratory of Dr. Jacek Hawiger
"The Expression, Turnover, and Reconstitution of SOCS-3 During Endotoxin-Induced Septic Shock"
Septic Shock Syndrome, an acute systemic inflammatory disorder caused by Gram- negative and Gram-positive bacteria, is characterized by unregulated cytokine production, multi-organ damage and vascular collapse. By using a model of endotoxic lipopolysaccharide (LPS)-induced Septic Shock, we were able to counteract the lethal effects of LPS with a novel intracellular protein therapy (IPT) based on a cell-penetrating form of Suppressor of Cytokine Signaling-3 (CP-SOCS3). SOCS3 is a known physiologic inhibitor of the JAK/STAT pathway as well as LPS-activated IRAK1/TRAF6 and TRIF/TRAF3 pathways. An unanticipated benefit of using CP-SOCS3 in vivo is its persistence in blood leukocytes/lymphocytes and spleen cells, suggesting different intracellular kinetics for this bioengineered protein. Comparative analysis of endogenous and cell-penetrating forms of SOCS3 turnover allows us to elucidate the mechanism of its persistence and to develop CP-SOCS3 variants that would offer more effective IPT against LPS-induced lethal shock.