Neil Grimsey, Ph.D.

Pharmaceutical and Biomedical Sciences
Assistant Professor

Pharmaceutical and Biomedical Sciences

Education

Postdoctoral training, Department of Pharmacology, University of California, San Diego 2009

Ph.D., Clinical Biochemistry, Cambridge University, Cambridge, England 2009

B.S., Cell and Molecular Biology, Ruskin University, Cambridge, England 2005

Honors, Awards, and Achievements

 

American Heart Association, Western Affiliates, Postdoctoral Fellowship, 2012

Medical research Council, UK. Graduate Student Stipend, 2008

Affiliations

American Heart Association

American Society for Cell Biology

American Society for Pharmaceutical and Experimental Therapeutics

Research Interests

The Grimsey lab focuses on the impact of G protein-coupled receptor (GPCR) mediated non-canonical p38 Mitogen Activated Protein (MAP) kinase signaling in vascular inflammation, angiogenesis and chronic lung disease. Our laboratory fosters a collaborative working environment, taking a multidisciplinary approach to address our research goals. In addition to using primary human vascular cells, some of the key techniques currently used in the laboratory are live cell fluorescence imaging, in vitro and in vivo angiogenesis models, and the development of novel Fluorescence Resonance Energy Transfer (FRET) biosensors, inhibitor peptides and therapeutic biologics.

The p38 mitogen-activated protein kinase (MAPK) pathway is a key mediator of vascular inflammatory responses in lung disease and is an important drug target for the treatment of chronic obstructive pulmonary disease (COPD) and cancer. Despite the wealth of information available, it is still unclear exactly how p38 MAPK signaling pathways are regulated by many GPCRs, with current p38 targeted therapies having failed to meet clinical needs.

GPCRs and MAPK-dependent signaling pathways regulate many physiological and pathophysiological processes and are the principle targets of more than 50% of current therapeutics.

Our studies have revealed a novel mechanism for GPCR dependent activation of non-canonical p38 signaling. Defining how non-canonical p38 signaling is regulated will enable us to identify new strategies and alternative targets for drug development.

Our research focus is driven by two key questions: 1) How do cells regulate the spatiotemporal kinetics of signaling cascades? and 2) How can we harness these processes to treat chronic inflammatory diseases?

Molecular Biology, Cell Biology, Vascular Biology, Biochemistry, Bioinformatics, Live Cell Microscopy, Drug Discovery, Pharmacology, Cell Signaling.

 

Selected Publications

Kroeger H, Grimsey N, Paxman R, Chiang WC, Plate L, Jones Y, Shaw PX, Trejo J, Tsang          SH, Powers E, Kelly JW, Wiseman RL, Lin JH. The unfolded protein response regulator ATF6 promotes mesodermal differentiation. Sci Signal. 2018 Feb 13;11(517). pii:                    eaan5785. doi: 10.1126/scisignal.aan5785. PubMed PMID: 29440509.

Dores MR, Grimsey NJ, Mendez F and Trejo J. (2016) ALIX Regulates the Ubiquitin Independent Lysosomal Sorting of the P2Y1 Purinergic Receptor via a YPXL Motif. PLoS One. Jun 14;11(6):e0157587

Grimsey NJ and Trejo J. (2016) Integration of Endothelial Protease-Activated Receptor-1 Inflammatory Signalling by Ubiquitin. Curr. Opin. Hematol. May;23(3):274-9

Grimsey NJ, Coronel LJ, Cordova IC, and Trejo J. (2016) Recycling and Endosomal Sorting of Protease-Activated Receptor-1 Is Distinctly Regulated by Rab11A and Rab11B Proteins. J. Biol Chem. Jan 29;291(5):2223-36. doi:10.1074/jbc.M115.702993

Dores MR, Lin H, Grimsey NJ, Mendez F and Trejo J. (2015) The -Arrestin ARRDC3 Mediates ALIX Ubiquitination and G Protein-Coupled Receptor Lysosomal Sorting. Mol. Biol. Cell. Dec 15;26(25):4660-73. doi: 10.1091/mbc.E15-05-0284.

Grimsey NJ, Aguilar, B, Smith TH, Le P, Soohoo AL, Puthenveedu MA, Nizet V and Trejo J. (2015) Ubiquitin Plays an Atypical Role in GPCR-Induced p38 MAP Kinase Activation on Endosomes. J. Cell Biol. 10.1083/jcb.201504007

Link to full publication list:

https://www.ncbi.nlm.nih.gov/sites/myncbi/1juk4niEZdk5w/bibliography/40445248/public/?sort=date&direction=ascending