The research effort in this laboratory is focused on elucidating nitric oxide-dependent signaling pathways in the cardiovascular systems subject to redox control.
Nitric oxide (NO) plays an essential role in a wide range of cardiovascular activities. NO bioactivity is effected, at least in significant part, through S-nitrosylation -- the adduction of an NO group and cysteine thiol to form an S-nitrosothiol (SNO). S-nitrosylation has been shown to regulate proteins in most functional classes and subserves paracrine and endocrine actions of NO by stabilizing its activity.
We study the molecular mechanisms by which SNOs (both endogenously produced or pharmacologically generated) regulate cardiovascular functions, ranging from cardiac contractility to arteriosclerosis. In addition, we study impairments in red blood cell function that may impact O2 delivery to tissues, and we design molecules to treat cardiovascular diseases.
Techniques employed include:
- Synthetic organic and inorganic chemistry
- Cell biology with emphasis on redox systems
- Pharmacology (bioassays) in heart, smooth muscle, skeletal muscle, and platelets
- Large animal physiology
- Hare JM, Stamler JS, NO/Redox disequilibrium in the failing heart and cardiovascular system. J. Clin Invest 115:509-517, 2005.
- Xu L, Eu JP, Meissner G, Stamler JS. Activation of the cardiac calcium release channel (ryanodine receptor) by poly S-nitrosylation. Science279:234-237, 1998.
- Hess DT, Matsumoto A, Kim SO, Marshall HE, Stamler JS. Protein S-nitrosylation: Purview and Parameters. Nature Rev Mol Biol 6: 151-164, 2005.
- Singel DJ, Stamler JS. Blood traffic control. Red blood cell vasodilation: nitric oxide and haemoglobin help to match blood flow to metabolic demand. Nature 430:297, 2004.
- Chen Z, Foster MW, Zhang J, Mao L, Rockman HA, Kawamoto T, Kitagawa K, Nakayama KI, Hess DT, Stamler JS. An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin bioactivation. Proc Natl Acad SciUSA, 102:12159-12164, 2005.
Jonathan Stamler, MD, Director
Office: 321 MSRB, Durham, NC, 27710
Campus mail: DUMC Box 2612, Durham, NC, 27710