UCR

Institute for Integrative Genome Biology



Members


Kathryn DeFeaKathryn DeFea

Associate Professor of Biomedical Sciences

Mailing Address:

Biomedical Sciences
Webber Hall /1116A
University of California
Riverside, CA 92521

Phone: (951) 827-2871
Fax: (951) 827-5504
Email: katie.defea@ucr.edu

Website

Degree(s):

PhD 1994 University of California, San Francisco
BA  University of California, Berkeley

College/Division Affiliation:

Division of Biomedical Sciences

Center/Inst Affiliation(s):

Center for Research in Intelligent Systems (CRIS)

Areas Of Expertise:

Regulation of Protease-activated-receptor Signaling in Inflammation and Cancer; Beta-arrestin-dependent Scaffolding of Signaling Molecules; Beta-arrestin-dependent Chemotaxis

Awards / Honors:

2001-2004 University of California, Office of the President New Investigator Award
2000 CURE Pilot and Feasibility Award "Neurokinin-1 Receptor Regulation of MAPK Cascades" 
1995-97 NIH NRSA, "A Cellular Mechanism for Insulin Resistance" 
1990-93 ARCS Graduate Dissertation Scholarship

Research Summary:

A number of receptors generate signals that converge at the activation of protein and lipid kinases, yet they are still able to elicit specific downstream effects, such as cell motility and proliferation. Furthermore, a number of receptor-mediated events require precise spatial and temporal control over these signaling molecules. A perfect example is directed cell motility or chemotaxis, in which a cell senses a chemical signal from one direction and must polarize itself in order to move towards the chemotactic agent. In this example, a receptor must generate conflicting signals in different parts of the cell-so that actin assembly in the front (aka leading edge) allows the cell to extend a lamellipodia in the direction of the signal, while this same process is silenced in the back of the cell. An increasingly common theme in cell biology is the concept that molecular scaffolds can serve not only to bring proteins in a signaling cascade together, but also to localize their activity to specific cellular microdomains. We have focused on the mechanisms by which different G-protein coupled receptors can utilize such protein scaffolding complexes to direct the subcellular localization of promiscuous signaling activities, in order to promote specific downstream events. We have purified two such complexes, which we have dubbed "endosomal scaffolds", because of their common requirement for binding to clathrin adaptor proteins of the beta-arrestin family. One such endosomal scaffold is induced upon activation of Protease Activated Receptor 2 (PAR2), leading to actin assembly and cell motility. Current projects include a molecular characterization of the role of beta-arrestins in localized actin assembly through regulation of filament severing, capping and nucleation promoting proteins. We are also investigating the physiological consequences of formation of beta-arrestin-dependent PAR-2 sigaling, and the possibility that PAR2-induced chemotaxis plays a role in tumor metastasis and recruitment of inflammatory cells during conditions such as IBD and asthma. A third project follows up on an exciting new discovery that beta-arrestins can act as a molecular switch in a cell-type specific manner to inhibit enzymes such as phosphatidylinositol-3 Kinase and AMP-regulated Kinase; dysregulation of both are associated with insulin resistance and metabolic syndrome.

Selected Publications:

List of publications from PubMed

Lab Personnel: 

Wang, Ping
Postdoctoral Researcher — PAR-2 Dependent PI3K Activity; b-arrestin-dependent Regulation of PI3K and AMPK, b-arrestins and Metabolic Disease
Kumar, Puneet
Graduate Student Researcher — PAR2/B-arrestin Interactions; Signal Desensitization
Lau, Mike
Postdoctoral Researcher — Graduate Student Researcher — PAR2 Induced Bacterial Uptake; Role of b-arrestins; PI3K and MAPKs
Mathur, Maneesh
Graduate Student Researcher — PAR2 Signaling Scaffolds and MAPK Localization
Min, Jungah
Graduate Student Researcher — PAR-2 Post-translational Modifications; Signaling Specificity in Response to Tethered and Glycosylated Ligands
Zoudilova, Maria
Graduate Student Researcher — Beta-arrestin-dependent Chemotaxis in Asthma

More Information

General Campus Information

University of California, Riverside
900 University Ave.
Riverside, CA 92521
Tel: (951) 827-1012

Career OpportunitiesUCR Libraries
Campus StatusDirections to UCR

Genomics Information

Institute of Integrative Genome Biology
2150 Batchelor Hall

Tel: (951) 827-7177
E-mail: Aurelia Espinoza, Managing Director

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