Senior Research Scientist
- 2000-date: "DCU Educational Trust" Senior Research Fellow, School of Biotechnology, Dublin City University.
- 1999-2000: Lecturer in Biology, Dept. of Applied Science, Institute of Technology, Tallaght, Dublin.
- 1996-1999: Postdoctoral Research Fellow, Dept. of Neurobiology, Mount Sinai School of Medicine, NY, USA.
- 1991-1995: Ph.D. in Biochemistry, School of Biotechnology, Dublin City University.
- 1987-1991: B.Sc. in Biotechnology, School of Biotechnology, Dublin City University.
Ongoing Research
- Characterization of the roles of inhibitory Gia-/Gbg-subunits and integrins in vascular endothelial cell signaling pathways in response to hemodynamic forces
Transduction of mechanical or hemodynamic forces (i.e. shear stress and cyclic strain - generated by the pulsatile flow of blood within vessels) in vascular cells involves a complex interplay between cytoskeletal and biochemical elements and results in changes in structure, metabolism, and gene expression. How these physical stimuli are transduced intracellularly resulting in quantitative and qualitative changes in gene expression however, is largely unknown. Several receptor proteins that have been implicated in the response of vascular endothelial cells (ECs) to hemodynamic challenge include ion channels, integrins, G-protein coupled receptors, and MAP kinases (MAPKs). Recent investigations in this lab (and other labs) have also implicated both pertussis toxin-sensitive (Gia1,2,3) and insensitive (Gaq) heterotrimeric G-protein a-subunits in the shear stress-induced release of endothelial vasoactive substances.
Considering the multiplicity and complexity of the signaling molecules engaged in EC responses to hemodynamic forces, there is a missing or poorly understood link to integrate the various pathways into a unified theme by enabling the activation of shear-sensitive cell surface receptors (such as integrins) to be coupled to cellular responses such as enhanced production of endogenous vasodilators (e.g. nitric oxide and prostacyclins). Our central hypothesis is that mechanical forces stimulate cell signaling processes in vascular endothelial cells by activating, in part, inhibitory guanine nucleotide regulatory proteins on the cell membrane. This project therefore involves a comprehensive examination of the role(s) of inhibitory guanine nucleotide regulatory G-protein alpha (Gia) and betagamma (Gbg) subunits in transducing mechanical forces from the cell membrane of vascular ECs using both molecular and pharmacological approaches to abolish EC Gia- and Gbg-subunit expression/activity.
Additional Research Interests:
- Hemodynamic regulation of peptide processing metalloenzymes within the mammalian vasculature
- Vascular Proteomics: Hemodynamic regulation of the vascular endothelial and smooth muscle cell 'proteome'
Recent Publications
- Tullai, J.W., Cummins, P.M., Pabon, A., Roberts, J.L., Lopingco, M.C., Shrimpton, C.N., Smith, A.I., Martignetti, J.A., Ferro, E.S. and Glucksman, M.J. (2000). The neuropeptide processing enzyme EC 3.4.24.15 is modulated by protein kinase A phosphorylation. J Biol Chem 275: 36514-36522.
- Crack, P.J., Wu, T.J., Cummins, P.M., Ferro, E.S., Tullai, J.W., Glucksman, M.J. and Roberts, J.L. (1999). The association of the metalloendopeptidase EC 3.4.24.15 at the extracellular surface of the AtT-20 cell plasma membrane. Brain Res 835: 113-124.
- Cummins, P.M., Pabon, A., Margulies, E.H. and Glucksman, M.J. (1999). Zinc coordination and substrate catalysis within the neuropeptide processing enzyme endopeptidase EC 3.4.24.15: identification of active site histidine and glutamate residues. J Biol Chem 274: 16003-16009.
- Cummins, P.M. and O'Connor, B. (1998). Pyroglutamyl peptidase: an overview of the three known enzymatic forms. Biochem Biophys Acta 1429: 1-17.
- Cummins, P.M. and O'Connor, B. (1996). Bovine brain pyroglutamyl aminopeptidase (type-I): purification and characterization of a neuropeptide-inactivating peptidase. Int J Biochem Cell Biol 28: 883-893.
Recent Abstracts/Posters
- Von Offenberg Sweeney, N., Birney, Y., Cummins, P.M. and Cahill, P.A. (2002). Cyclic strain Induces pro-MMP2 release from bovine aortic endothelial cells via a Gia protein-independent pathway and via a MAP kinase-dependent pathway. ExBio 2002 FASEB Meeting: 'Translating the Genome', New Orleans, LA.
- Cummins, P.M., Coen, P.M. and Cahill, P.A. (2001). Regulation of endopeptidase EC 3.4.24.15 expression in vascular endothelial cells by mechanical forces. Supplement to Circulation 104: 298. [peer reviewed poster - American Heart Association, Anaheim, CA]
- Coyle, S., Birney, Y., Cummins, P., Sweeney, C., Walls, D. and Cahill, P.A. (2001). The role of notch signalling in aortic vascular smooth muscle cells. Ir J Med Sci 170 (suppl 2): 116.
- Von Offenberg Sweeney, N., Coen, P., Cummins, P. and Cahill, P.A. (2001). Shear stress induced pro-MMP2 activity in bovine aortic endothelial cells via an inhibitory Gi protein. Ir J Med Sci 170 (suppl 2): 124.
- Birney, Y., Coyle, S., Cummins, P. and Cahill, P.A. (2000). Mechanical forces and vascular cell signalling-how vascular cells respond to stress. 12th Annual Meeting of the Irish Association of Pharmacologists, Dublin, Ireland.
- Birney, Y., Cummins, P. and Cahill, P.A. (2000). Vascular biology/tissue engineering. The Irish Scientist 8: 126.
