Cardiovascular disease is the major cause of death and morbidity in the United States and worldwide. Many of these disorders involve abnormal growth of vascular smooth muscle, the primary muscular tissue in vessels. One of such disorders is atherosclerosis, a form of arteriosclerosis in which the arteries harden and narrow due to fat deposited on the inside walls. As the artery narrows both the oxygen and blood supply to the affected organ is reduced resulting in heart attack or stroke. This condition is normally treated by medical intervention which results in restenosis, narrowing of the blood vessel due to abnormal growth of vascular tissue.
The primary focus of my work in Dr. Tulis' lab is to elucidate the cellular and molecular mechanism which results in the abnormal growth of vascular tissue. There are cascades of events which lead to this phenomenon. However, our primary focus is on cyclic nucleotide signaling. The cyclic nucleotides cGMP and cAMP are key secondary signaling molecules in many cellular processes including those associated with vascular growth. Specifically my focus is on understanding how the phosphodiesterases present regulate the cyclic nucleotides to control growth and how exchange proteins regulated by cAMP are involved in this process.
Regulation of vascular smooth muscle cell proliferation and growth is essential to preservation of blood vessel integrity, as hyperplasia or hypertrophy can result in development of cardiovascular diseases or vascular complications. Cyclic nucleotides are considered antiproliferative in vascular tissues and its signaling has been the target of basic science research and clinical studies for the development of therapeutics. Since vascular smooth muscle cell growth is an integral process in the pathophysiology of numerous cardiac and vascular disorders; approaches aimed at minimizing abnormal vascular smooth muscle growth would be of great clinical and therapeutic interest.
Education and Training
Bachelor of Science in Biochemistry with a minor in Chemistry, Louisiana State University, Baton Rouge, LA.
Doctor of Philosophy, Pharmacology and Physiology, Saint Louis University, School of Medicine, Saint Louis, MO.
Adderley, SP., et al., "Iloprost-and isoproterenol-induced increases in cAMP are regulated by different phosphodiesterases in erythrocytes of both rabbits and humans," (Am J Physiology Heart Circ, 2009)
Adderley, SP., et al., "Regulation of cAMP by Phosphodiesterases in Erythrocytes," (Pharmacological Reports, 2010)
Adderley, SP., et al., "Protein Kinases A and C Regulate Receptor-Mediated Increases in cAMP in Rabbit Erythrocytes," (Am J Physiology-Heart Circ, 2009)
Adderley, SP., et al., "Identification of cytosolic phosphodieserases in the erythrocyte: A role for PDE5," (Medical Science Monitor, 2011)
Adderley, SP., et al., "EPACs inhibit receptor-mediated ATP release from Erythrocytes (RBCs) possibly via activation of PKC," (Microcirculation, 2011)