Our primary research interest is in the assembly and regulation of the cytoskeleton. We are studying the function of membrane-associated guanylate kinase homologues in the regulation of cell polarity pathways. MAGUKs are scaffolding proteins composed of PDZ, SH3, and GUK domains regulating multiple protein-protein assemblies in erythrocytes, neurons, epithelia, lymphocytes, and neutrophils. We pursue these studies using genetically modified mice as models of cell polarity and tumorigenesis. A second project is investigating the signaling functions of calpain-1 and its substrates in cell secretion, adhesion, motility, and apoptosis pathways. The objective of these studies is to identify new pharmacological targets of cardiovascular dysfunctions. The aim of the third study is to determine the mechanisms of malaria parasite pathogenesis in human red blood cells with the long-term goal of developing novel drugs and vaccine against malaria. We use genetically modified mice of calpain-1, dematin, p55/MPP1, and band 3 as experimental tools to facilitate these studies.

Lab Members

• Chishti, A.H., Levin, A.L. and Branton, D. (1988). Abolition of actin-bundling by phosphorylation of human erythrocyte protein 4.9. Nature 334: 718-721.
  
  
• Ruff, P., Speicher, D.W. and Chishti, A.H. (1991). Molecular identification of a major palmitoylated erythrocyte membrane protein containing the SH-3 (src homology-3) motif. Proc. Natl. Acad. Sciences. USA 88: 6595-6599.
  
  
• Rana, A.P., Ruff, P., Maalouf, G.J., Speicher, D.W. and Chishti, A.H. (1993). Cloning of human erythroid dematin reveals another member of the villin family. Proc. Natl. Acad. Sci. USA 90: 6651-6655.
  
  
• Marfatia, S.M., Lue, R.A., Branton, D. and Chishti, A.H. (1994). In vitro binding studies suggest a membrane-associated complex between erythroid p55, protein 4.1, and glycophorin C. J. of Biological Chemistry 269: 8631-8634.
  
  
• Lue, R.A., Marfatia, S.M., Branton, D. and Chishti, A.H. (1994). Cloning and characterization of hdlg: the human homologue of the Drosophila discs-large tumor suppressor binds to protein 4.1. Proc. Natl. Acad. Sci. USA 91: 9818-9822.
  
  
• Morais-Cabral, J.H., Petrosa, C., Poy, F., Marfatia, S.M., Chishti, A.H., Liddington, R.C. (1996). Crystal Structure of a PDZ domain from the human homologue of discs-large protein. Nature 382:649-652.
  
  
• Marfatia, S.M., Morais-Cabral, J.H., Lin, L., Hough, C., Bryant, P.J., Stolz, L., Chishti, A.H. (1996). Modular organization of the PDZ domains in the human discs large protein suggests a mechanism for coupling PDZ domain binding proteins to ATP and the membrane cytoskeleton. J. Cell Biol. 135:753-766.
  
  
• Southgate, C.D., Chishti, A.H., Mitchell, B., Yi, S.J. and Palek, J. (1996). Targeted disruption of the murine erythroid band 3 gene results in spherocytosis and severe haemolytic anemia despite a normal membrane skeleton. Nature Genetics 14: 227-230.
  
  
• Songyang, Z., Fanning, A.S., Fu, C., Xu, J., Marfatia, S.M., Chishti, A.H., Crompton, A., Chan, A.C., Anderson, J.M. and Cantley, L.C. (1997). Recognition of unique carboxyl-terminal motifs by distinct PDZ domains. Science 275:73-77.
  
  
• Roof, D.J., Hayes, A., Adamian, M., Chishti, A.H., and Li, T. (1997). Molecular characterization of abLIM, a novel actin-binding and double zinc finger protein. J. Cell Biol. 138:575-588.
  
  
• Chishti, A.H., Kim, A.C., Marfatia, S.M., Lutchman, M., Hanspal, M., Jindal, H., Liu, S-C., Low, P.S., Rouleau, G.A. et al. (1998). The FERM domain: A unique module involved in the linkage of cytoplasmic proteins to the membrane. Trends in Biochemical Sciences (TiBS) 23:281-282.
  
  
• Hanada, T., Lin, L., Tibaldi, E.V., Reinherz, E.L., and Chishti, A.H. (2000). GAKIN: A Novel Kinesin-like Protein Associates with the Human Homologue of the Drosophila Discs Large Tumor Suppressor in T Lymphocytes. J. of Biological Chemistry 275:28774-28784.
  
  
• Azam, M., Andrabi, S.S., Sahr, K.E., Kamath, L., Kuliopulos, A., and Chishti, A.H. (2001). Disruption of the mouse -calpain gene reveals an essential role in platelet function. Molecular and Cell Biology 21:2213-2220.
  
  
• Khanna, R., Chang, S.C., Andrabi, S., Azam, M., Kim, A., Rivera, A., Brugnara, C., Low, P.S., Liu, S-C., Chishti, A.H. (2002). Headpiece domain of dematin is required for the stability of the erythrocyte membrane. Proc. Natl. Acad. Sci. (USA) 99: 6637-6642.
  
  
• Goel, V.K., Li, X., Liu, S-C, Chishti, A.H., and Oh, S.S. (2003). Band 3 is a host receptor binding merozoite surface protein-1 during the Plasmodium falciparum invasion of erythrocytes. Proc. Natl. Acad. Sci. (USA) 100:5164-5169.
  
  
• Horiguchi, K., Hanada, T., Fukui, Y., Chishti, A.H. (2006). Transport of PIP3 by GAKIN, a Kinesin-3 Family Protein, regulates neuronal cell polarity. J. of Cell Biology 174, 425-436.
  
  
• Chen, H., Khan, A.A., Liu, F., Gilligan, D.M., Peters, L.L., Messick, J., Haschek-Hock, W.M., Li, X., Ostafin, A.E., and Chishti, A.H. (2007). Combined deletion of mouse dematin-headpiece and beta-adducin exerts a novel effect on the spectrin-actin junctions leading to erythrocyte fragility and hemolytic anemia. J. of Biological Chemistry 282, 4124-35.
  
  
• Li, X., Chen, H., Oh, S.S., Chishti, A.H. (2008). A Presenilin-like protease associated with Plasmodium falciparum micronemes is involved in erythrocyte invasion. Molecular Biochemical Parasitology 158:22-31.
  
  
• Mohseni, M. and Chishti, A.H. (2008). The headpiece domain of dematin regulates cell shape, motility, and wound healing by modulating RhoA activation. Molecular Cell Biology 28: 4712-4718.
  
  
• Li, X., Chen, H., Bahamontes-Rosa, N., Kun, J.F.J., Traore, B., Crompton, P.D., and Chishti, A.H. (2009). Plasmodium falciparum signal peptide peptidase is a promising drug target against blood stage malaria. Biochemical and Biophysical Research Communications 380: 454-459.