University of Iowa
Department of Biochemistry
4-403 BSB
Iowa City, IA 52242-1109 USA phone: 877-846-8569
or 319-335-7932
fax: (319) 335-9570
biochem@uiowa.edu

Department of Biochemistry

Assistant Professor of Biochemistry, PhD

Office: 4-470 BSB
Phone: (319) 335-7882
Fax: (319) 335-9570
kris-demali@uiowa.edu

Kris A. DeMali
51 Newton Rd
Biochemistry/Univ. of Iowa
Iowa City, IA 52242

Research Interests

Figure 2. Adherens junction components

Cell-cell interactions affect many aspects of cell behavior, including growth, differentiation and the establishment of normal tissue architecture. Loss of expression or function of components present in cell-cell interactions has been found in carcinomas and correlates with poor prognostic outcome in cancer patients. Cells have several mechanisms for linking to their neighbors. These so-called "cell junctions" consist of proteins that assemble into different structures such as gap junctions, tight junctions, adherens junctions, desmosomes and hemidesmosomes, each with specialized functions. Cell-cell junctions of the zonula adherens are prominent in epithelia and are rich in transmembrane adhesive receptors known as cadherins. The cytoplasmic tail of cadherins binds numerous proteins that serve as molecular couplers, linking cell surface adhesion and recognition to both the actin cytoskeleton and cell signaling pathways. A major focus of the work in my lab is to understand cellular mechanisms involved in assembly and maintenance of cell-cell adhesions by examining the function and regulation of proteins recruited to the cytoplasmic face of cadherins.

Figure 1. Visualization of cell-cell adhesions in kidney epithelial cells.

A second focus of my research is to better understand the disassembly of cell-cell adhesions. Dysregulation of cell-cell contacts is essential for a metastasizing tumor cell to escape the normal tissue confines and penetrate connective tissue barriers. In my lab, the loss of cell-cell adhesions will be studied. For these experiments, the Shigella protein, IpaA, will be used as a tool to mimic the disruption of cell-cell adhesions that occurs during tumor cell metastasis and invasion, and the disassembly of adhesion complexes will be examined using a combination of biochemical methods and live cell imaging techniques. Through this work we hope to gain a better understanding of the mechanisms underlying tumor cell invasion and metastasis.

Recent Publications

DeMali, K.A., Jue, A.L., Burridge, K. (2006) IpaA targets b1 integrins and Rho to promote actin cytoskeleton rearrangements necessary for Shigella entry. J. Biol. Chem. 281:39534-39541.

DeMali, KA. (2004) Vinculin-a dynamic regulator of cell adhesion TiBS, 29:565-67.

Ellerbroek, SM, Wennerberg, K., Arthur, WT, Dunty, JM, Bowman, DR, DeMali, KA, Der, C., Burridge, K. (2004) SGEF, a RhoG guanine nucleotide exchange factor that stimulates macropinocytosis. Mol Biol Cell 15:3309-3319..

DeMali, K.A., Wennerberg, K. and Burridge, K. (2003) Integrin signaling to the actin cytoskeleton. Curr. Opin Cell Biol. 15:572-582..

DeMali, K.A. and Burridge, K. (2003) Coupling membrane protrusion and cell adhesion. J. Cell Sci. 116:2389-2397.

DeMali, K.A., Barlow, C.A. and Burridge, K. (2002) Regulated binding of the Arp2/3 complex to vinculin. J. Cell Biol. 159:881-891.

Affiliations

Biochemistry Department
Molecular and Cellular Biology Program
Holden Comprehensive Cancer Center