Maurice | Biomedical and Molecular Sciences | School of Medicine

Donald H. Maurice PhD

Position(s)

Professor

Contact Info

613-533-6000 x75089

Faculty Bio

The Maurice Lab is interested in investigating the role of cyclic nucleotide (cAMP and cGMP) compartmentation and cyclic nucleotide signaling in human vascular cells including arterial endothelial cells and arterial smooth muscle cells. Since virtually all cells are either directly or indirectly influenced by cAMP and or cGMP, this system represents a potential therapeutic target in multiple cardiovascular diseases such as atherosclerosis and restenosis, and is important processes such as angiogenesis.

Our laboratory investigates how signal compartmentation allows cAMP to regulate simultaneously myriad cellular events with specificity. Overall, our work shows that Cyclic Nucleotide Phosphodiesterase (PDEs), the sole enzymes that inactivate cAMP by hydrolysis, are critical for specificity in this system. In addition, while our studies demonstrate that PDEs are highly “druggable”, they also identify critical shortcoming in current targeting approaches. Specifically, although humans can generate >100 unique PDE variants, and PDEs are known to operate within unique cAMP signaling compartments in cells, current therapeutic strategies have failed to capitalize on their highly compartmented actions. Indeed, most approaches focus on findings agents that inhibit selected PDE activities by catalytic site inhibition without considering the hyper-localized nature of their actions (review Maurice et al., Nature Reviews, Drug Discovery, 13:290, 2014)1. The research elaborated here is a comprehensive plan to identify strategies that will allow inhibition of PDEs in their “natural environment” (i.e. in compartments) and to begin to translate these strategies into approaches to limit the mal-adaptive consequences of atherosclerosis and angiogenesis.

Further information available at MauriceLab.com

Research Interests

The Maurice lab investigates the role that subcellular compartment-specific hydrolysis of cyclic nucleotide (cAMP and cGMP), by the cyclic nucleotide phosphodiesterases (PDEs), plays in promoting selective cyclic nucleotide-signaling in human arterial endothelial and smooth muscle cells. Since virtually all functions of these cell types are regulated by cyclic nculeotide-signaling systems, our studies may allow identification of novel therapeutic targets for managenment of multiple cardiovascular diseases, including atherosclerosis and restenosis, and in important vascular processes such as vasculogenesis and angiogenesis.

Selected Publications

Wilson LS, Guo M, Umana MB, Maurice DH. Distinct phosphodiesterase 5A-containing compartments allow selective regulation of cGMP-dependent signalling in human arterial smooth muscle cells. Cell Signal. 2017 36:204-211.

Rampersad SN, Freitag SI, Hubert F, Brzezinska P, Butler N, Umana MB, Wudwud AR, Maurice DH. EPAC1 promotes adaptive responses in human arterial endothelial cells subjected to low levels of laminar fluid shear stress: Implications in flow-related endothelial dysfunction. Cell Signal. 2016 28:606-19.

Rampersad SN, Wudwud A, Hubert F, Maurice DH. Adaptive phenotypic modulation of human arterial endothelial cells to fluid shear stress-encoded signals: Modulation by phosphodiesterase 4D-VE-cadherin signalling. Cell Signal. 2016 28:741-8.

Maurice DH, Ke H, Ahmad F, Wang Y, Chung J, Manganiello VC. Advances in targeting cyclic nucleotide phosphodiesterases. Nat Rev Drug Discov. 2014 13:290-314.

Maurice DH. PDE8A runs interference to limit PKA inhibition of Raf-1. Proc Natl Acad Sci U S A. 2013 110:6248-9.

Wilson LS, Baillie GS, Pritchard LM, Umana B, Terrin A, Zaccolo M, Houslay MD, Maurice DH. A phosphodiesterase 3B-based signaling complex integrates exchange protein activated by cAMP 1 and phosphatidylinositol 3-kinase signals in human arterial endothelial cells. J Biol Chem. 2011 286:16285-96.

Rampersad SN, Ovens JD, Huston E, Umana MB, Wilson LS, Netherton SJ, Lynch MJ, Baillie GS, Houslay MD, Maurice DH. Cyclic AMP phosphodiesterase 4D (PDE4D) Tethers EPAC1 in a vascular endothelial cadherin (VE-Cad)-based signaling complex and controls cAMP-mediated vascular permeability. J Biol Chem. 2010 285:33614-22.

Team

Faculty Bio

Research Interests

Selected Publications

Maurice, Donald H. Lab

Faculty