Assistant Professor
Scott & White Memorial Hospital
Texas A&M Health Science Center
702 S.W.H.K Dogen Loop (MRB, office 218)
Temple, Texas 76504
Medical Research Building, Office # 218
Phone: 254-724-7989

Research Interests

Structures and Functions of Cell Signaling Proteins

My research includes the studies of the structure and dynamics of ras-like GTPases, such as Cdc42Hs and Arf6 using biophysical techniques such as nuclear magnetic resonance (NMR), which play important roles in the regulation of cell proliferation, differentiation and cytoskeleton organization by binding to different effectors which initiate a cascade of protein-protein interactions. Activation of Cdc42Hs initiates a cascade of kinase interactions from the plasma membrane to the nucleus which leads to the activation of two nuclear stress-responsive MAP kinases, JNK1 and p38 and cytoskeletal reorganization. A variety of effectors have been identified and include the p85 subunit of the PI3 kinase, the Wiscott-Aldrich syndrom protein WASP, the ACK tyrosine kinase, and p21 activated serine/threonine kinase (PAK). In several cases (e.g., WASP, ACK, PAK), these effectors have a common binding region which is known as CRIB (Cdc42Hs-rac interactive binding) domain . We have determined the structure of the complex Cdc42Hs and a 46 amino acid peptide derived from PAK using NMR spectroscopy. Arf6 regulates changes in the actin cytoskeleton and the movement of the plasma membrane into and out of an endosomal recycling pathway. This membrane recycling pathway is involved in cell spreading and Rac1-mediated cell ruffling. This suggests that Arf6 may be a critical component in the cell shape alterations that occur during cell migration, differentiation and metastasis. Considering the importance of membrane association to the function of most, if not all, G proteins, knowledge of the orientation of the protein with respect to the membrane, the effect of lipid modification and the interface of the protein with the membrane is of considerable importance.

Selected Publications

Dawit Gizachew*, Robert Oswald. "NMR structural studies of the myristoylated N-terminus of ADP ribosylation factor 6 (Arf6)." FEBS Letters 580 (2006) 4296-4301.

Dawit Gizachew and Robert E. Oswald. "Concerted Motion of a Protein-Peptide Complex: Backbone Dynamics Studies of an 15N-Labeled Peptide Derived from P21- Activated Kinase Bound to Cdc42Hs.GMPPCP." Biochemistry 40 (2001) 14368-14375.