Angela Glading, Ph.D.

Angela Glading, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 711
Rochester, NY 14642

Office: (585) 273-5750
Lab: (585) 273-3043
Fax: (585) 273-2652

Research Bio

In order for normal cells to function, they must adhere to their immediate environment, which includes other cells and proteins. In return, cells receive both mechanical and chemical signals from their environment that are important for cellular processes such as migration, proliferation, and gene expression. Defective or improperly regulated adhesion is observed in a wide variety of human diseases, including the major killers cancer and cardiovascular disease.



Research in the Glading lab focuses on unraveling how cell adhesion signaling regulates cellular behavior.

Currently, our work concentrates on how cell-cell adhesion modulates cell growth and differentiation in both the normal and disease state. Our main experimental context is the endothelial cell and the intact blood vessel. Vessel function is reliant on the ability of vessels to maintain an effective barrier between the blood and tissue, which is primarily regulated at the level of the endothelial cell-cell contact (endothelial junctions). Changes in this barrier regulate the normal immune response and contribute to the growth of new vessels (angiogenesis).

Recently, we described KRIT1 as a scaffolding protein that nucleates a signaling complex at sites of endothelial cell-cell contact. In confluent endothelial cells, the KRIT1 complex associates with cell-cell contacts and is required for junctional stability downstream of active Rap1 (Glading et al 2007). KRIT1 also sits at the nexus of multiple signaling pathways, including the canonical beta-catenin pathway (Glading and Ginsberg, 2010), vascular-endothelial growth factor receptor (VEGFR) activation (DiStefano and Glading, in press), RhoA/Rho Kinase activity (Glading et al, 2007), and Notch signaling, which KRIT1 supports or modifies to promote a stable vascular barrier. Our ongoing research aims to understand cell-cell contact impacts global cell signaling by examining how KRIT1 signaling contributes to changes in cellular behavior.

We use KRIT1 deficient endothelial cells (siRNA, CRISPR) and tissues (KRIT1 knockout and KRIT1 endothelial-specific knockout mice) as models to probe the consequence of loss of endothelial cell-cell contact on endothelial behavior and vessel integrity in vitro and in vivo. By using genetic manipulation of KRIT1, we have been able to prove that loss of cell-cell contact stimulates broad changes in gene expression (Glading, 2010), induces vascular permeability in vivo (Corr et al, 2012), and promotes angiogenesis (unpublished data), as just a few examples. By combining molecular and biochemical examination of specific signaling mechanisms with real-time physiology, we are able to establish key signaling events as critical for normal vascular function. In current research, we are using this approach to explore the crosstalk between inflammatory signaling, angiogenesis and cell-cell contact in the relevant physiological contexts of vascular integrity and cancer.

Awards & Honors (Local)

The Takashi Murachi Young Investigator Award | FASEB 2001

Recent Journal Articles

Showing the 5 most recent journal articles. 14 available »

2012 Nov
Corr M, Lerman I, Keubel JM, Ronacher L, Misra R, Lund F, Sarelius IH, Glading AJ. "Decreased Krev interaction-trapped 1 expression leads to increased vascular permeability and modifies inflammatory responses in vivo." Arteriosclerosis, thrombosis, and vascular biology.. 2012 Nov; 32(11):2702-10. Epub 2012 Aug 23.
2010
Glading AJ, Ginsberg MH. "Rap1 and its effector KRIT1/CCM1 regulate beta-catenin signaling." Disease models & mechanisms.. 2010 3(1-2):73-83. Epub 2009 Dec 09.
2007 Oct 22
Glading A, Han J, Stockton RA, Ginsberg MH. "KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions." The Journal of cell biology. 2007 Oct 22; 179(2):247-54.
2007 Feb 15
Glading A, Koziol JA, Krueger J, Ginsberg MH. "PEA-15 inhibits tumor cell invasion by binding to extracellular signal-regulated kinase 1/2." Cancer research.. 2007 Feb 15; 67(4):1536-44.
2005 Aug
Krueger J, Chou FL, Glading A, Schaefer E, Ginsberg MH. "Phosphorylation of phosphoprotein enriched in astrocytes (PEA-15) regulates extracellular signal-regulated kinase-dependent transcription and cell proliferation." Molecular biology of the cell.. 2005 Aug; 16(8):3552-61. Epub 2005 May 25.

Current Appointments

Assistant Professor - Department of Pharmacology and Physiology (SMD) - Primary
Assistant Professor - Department of Biomedical Engineering (SMD)

Education

Ph.D. | Cellular and Molecular Pathology | University of Pittsburgh2002
BS | Biochemistry and Biology | Whitworth College1997

Post-Doctoral Training & Residency

Department of Medicine, University of California San Diego, Supervisor: Mark H. Ginsberg 2008
Department of Cell Biology, The Scripps Research Institute, Supervisor: Mark H. Ginsberg 2004