Research Fellow, Division of Orthopaedic Research, Department of Orthopaedic Surgery, Thomas Jefferson
University, Philadelphia, PA.
Research Associate, Division of Endocrinology, Department of Medicine, Medical College of Pennsylvania-Hahnemann University, Philadelphia, PA.
Post-doctoral Fellow, Division of Bone and Mineral Research, Department of Medicine, Medical University of South Carolina, Charleston, SC.
Doctor of Philosophy, Pharmacology (Molecular Pharmacology), University of Alberta, Edmonton, Alberta, Canada.
Master of Science, Pharmacology, University of Alberta, Edmonton, Alberta, Canada.
Master of Science, Biochemistry, University of Ghana, Legon, Ghana.
Bachelor of Science, Biochemistry (major), Chemistry (minor), University of Ghana, Legon, Ghana
My research is focused on the characterization of the signaling mechanisms of the sensory nerve calcium-sensing receptor (CaR) with a long term goal of elucidating its role in vasodilation, hence blood pressure regulation. Our earlier studies have shown that extracellular calcium (Ca2+e) relaxed isolated, phenylephrine-contracted mesenteric branch arteries, a process dependent on an intact peri-vascular sensory nerve network. We hypothesized that elevation of Ca2+e in the interstitial compartment activates the sensory nerve CaR resulting in the production and release of a vasodilator compound that induces relaxation (Bukoski 1998; Am J Hypertens 11: 1117-1123).
We have amplified a CaR cDNA (3.9 kb) from dorsal root ganglia (DRG), which house cell bodies of sensory nerves, by RT-PCR and cloned it into a Green Fluorescent Protein vector (pEGFP). Expression of the fused CaR-EGFP protein was detected in the plasma membrane in Human Embryonic Kidney (HEK293) cells after transient transfection with CaR cDNA-pEGFP construct. Increasing Ca2+e from 0.5 –1.5 mM resulted in a transient rise in intracellular calcium concentration ([Ca2+]i). The results demonstrate functionality of the DRG CaR suggesting a role in sensory nerves and confirm CaR-associated [Ca2+]i oscillations (Wang et al., 2003; Am J. Physiol Cell Physiol 285:C64-C75). In addition we have shown that the receptor is desensitized upon repeated stimulation with agonist and that the signaling mechanism involves PKCα (Awumey et al., 2007; Am J. Physiol Cell Physiol 292:C1895-C1905).
We currently use state-of-the-art biochemical, pharmacological and molecular biology techniques to characterize the CaR and study its signal transduction mechanism in neuronal and non-neuronal cells. We employ cell culture, vector cloning, RT-PCR, [Ca2+]i imaging, confocal microscopy, western blotting, and immunochemistry in these studies. In addition, we are conducting studies with isolated resistance arteries from normal and hypertensive animals to determine potential signaling pathways that result in Ca2+e-induced blood vessel relaxation. We anticipate that these studies will lead to a more complete understanding of the molecular mechanisms linking Ca2+ homeostasis and vascular function and may provide the basis for the development of novel pharmacologic means of regulating blood pressure.
Physiology and Pharmacology II (BIOG 5401), Instructor.
Thesis (BIOG 5900), Advisor.
Derfoul A, Lin FJ, Awumey EM, Kolodzeski T, Hall DJ, Tuan RS. Estrogenic endocrine disruptive components interfere with calcium handling and differentiation of human trophoblast cells. J. Cell Biochem 89: 755-770, 2003.
Wang Y, Awumey EK, Chatterjee PK, Somasundaram C, Bian K, Rogers KV, Dunn C, Bukoski RD. Molecular cloning and characterization of a rat sensory nerve Ca2+-sensing Receptor. Am J. Physiol Cell Physiol 285: C64-C75, 2003.
Awumey EM, Howlett AC, Diz DI. Commentry: Is there a role for anandamide in cardiovascular regulation? Insights from studies of endocannabinoid metabolism. Am J Physiol Heart Circ Physiol 289: H520-H521, 2005.
Awumey EM, Bukoski RD. Cellular Functions and Fluxes of Calcium. In: Weaver CM, Heaney RP, eds. Calcium in Human Health, Totowa, NJ: Humana Press, Chp. 3, pp. 13-25, 2006.
Awumey EM, Howlett AC, Diz DI, Putney JW, Jr., Bukoski RD. Ca2+ mobilization through the Dorsal Root Ganglion Ca2+-sensing receptor stably expressed in HEK293 cells. Am J. Physiol Cell Physiol 292: C1895-C1905, 2007.
Heyeraas KJ, Haug SR, Bukoski RD, Awumey EM. Identification of the Ca2+-sensing Receptor in Rat Trigeminal Ganglia, Sensory Axons and Tooth Dental Pulp. Calc.Tissue Int. In press.
Awumey EM, Hill SK, Diz DI, Bukoski RD. Cytochrome P450 metabolites of 2-arachidonyl glycerol play a role in Ca2+-induced relaxation of isolated mesenteric arteries. Am J Physiol Heart Circ Physiol. Minor Revision.
Sesay J, Somasundaram C, Diz DI, Bukoski RD, Howlett AC Awumey EM. N18TG2 neuroblastoma cells express a Ca2+-sensing receptor coupled to intracellular Ca2+ signalling. Submitted.
Bukoski RD, Somasundaram C, Cogdell K, Howlett A, Awumey EM. N18TG2 cells express a Ca2+-sensing receptor coupled with intracellular Ca2+ signaling. Hypertension 42: P31, 2003.
Awumey EM, Bukoski RD. The IP3 receptor antagonist, 2-aminoethoxydiphenyl borate blocks [Ca2+]i transients and store-operated calcium entry in HEK293 cells expressing the sensory nerve Ca2+-sensing receptor. FASEB J. 18: A970, 2004.
Awumey EM, Putney JW, Jr., Howlett A, Bukoski RD. Desensitization of the sensory nerve Ca2+-sensing receptor stably expressed in HEK293 cells is mediated by protein kinase C. FASEB J. 19: A524, 2005.
Awumey EM, Hill SK, Diz DI, Bukoski RD. 2-Arachidonylglycerol and its metabolite, glycerated epoxy-eicosatrienoic acid mediate Ca2+-induced relaxation of isolated mesenteric arteries. Am J Hypertension 18: 50A, 2005.
Awumey EM, Hill SK, Kunos G, Diz DI, Bukoski RD. Ionized calcium, in the physiological range, induces the release and metabolism of anandamide and 2-arachidonyl glycerol in isolated mesenteric artery arcade. Hypertension 46: P21, 2005.
Awumey EM, Diz DI, Howlett AC, Putney JW, Jr. Downregulation of protein kinase C Inhibits perivascular sensory nerve Ca2+-sensing receptor signaling. Hypertension 48: E85, 2006.
Heyeraas KJ, Haug SR, Awumey EM. Identification of the Ca2+-sensing receptor in rat trigeminal ganglia, sensory axons and tooth dental pulp. FASEB J 21: A73, 2007.
Sesay J, Howlett AC, Diz DI, Awumey EM. Ca2+-sensing receptor signaling in mouse neuroblastoma cells: A model for the perivascular sensory nerve Ca2+-sensing receptor. Hypertension 50:e124, 2007.
R25 HL0552729 (PI, Harewood, KR): Research in Cardiovascular Health among African Americans
Agency: NIH/NHLBI
2R01 HL64761 (PI, Harewood, KR): Mechanisms Linking Ca2+ Homeostasis and Vascular Tone
Agency: NIH/NHLBI
Minority Research Supplement, Biomedical/ Biotechnology Research Institute, North Carolina Central University.
Agency: NIH/NHLBI
American Society for Pharmacology and Experimental Therapeutics.
American Physiological Society.
American Heart Association.