The 1998 Nobel Prize in Physiology or Medicine was awarded for the discovery that nitric oxide (NO) functions as an endogenous physiological mediator. It is now clear that NO, best characterized as a signaling molecule and cytotoxic agent, plays important roles in virtually every biological system. However, the current perspective on NO biology is centered predominantly around NO production, whereas the regulatory events downstream of NO synthesis, including in particular turnover of the NO-derived molecular modifications that mediate NO bioactivity, are much less well understood. NO regulates cellular function in large part through the covalent modification of cysteine thiols in peptides and proteins, forming S-nitrosothiols (SNO). Our goal is to elucidate the mechanisms essential for NO/SNO metabolism and their roles in health and disease. Our research has shown that cells possess a number of enzymes that specifically mediate NO/SNO metabolism, and that regulated turnover of NO/SNO plays critical roles in animal models of septic shock (Cell 116:617), asthma (Science 308:1618) and heart failure. |
Mannick JB, Hausladen A, Liu L , Hess DT, Zeng M, Miao QX, Kane LS, Gow AJ, Stamler JS (1999). Fas-induced caspase denitrosylation. Science 284:651-654. Liu L , Zeng M, Stamler JS. (1999) Hemoglobin induction in mouse macrophages. Proc Natl Acad Sci USA 96:6643-6647.
Liu L , Zeng M, Hausladen A, Heitman J, Stamler JS (2000). Protection from nitrosative stress by yeast flavohemoglobin. Proc Natl Acad Sci USA 97:4672-4676.
Liu L , Hausladen A, Zeng M, Loretta Que, Heitman J, Stamler JS (2001). A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans. Nature 410:490-494.
Matsumoto A, Comatas KE, Liu L , Stamler JS ( 2003 ). Screening for nitric oxide-dependent protein-protein interactions. Science 301:657-661.
Jesus-Berrios MD, Liu L , Nussbaum JC, Cox GM, Stamler JS, Heitman J (2003). Enzymes that counteract nitrosative stress promote fungal virulence. Current Biology 13:1963-1968.
Liu L , Yan Y, Zeng M, Zhang J, Hanes MA, Ahearn G, McMahon TJ, Dickfeld T, Marshall HE, Que LG, Stamler JS (2004). Essential roles of S -nitrosothiols in vascular homeostasis and endotoxic shock. Cell 116:617-628.
Que LG, Liu L , Yan Y, Whitehead GS, Gavett SH, Schwartz DA, Stamler JS (2005). Protection from experimental asthma by an endogenous bronchodilator. Science 308:1618-1621.
information last updated June 2005 |
Biomedical Sciences (BMS) Graduate Program
