Research Summary:

We are interested in defining the molecular basis of the lysosomal disorder known as the Chediak-Higashi Syndrome. This disease is caused by mutations in a very large gene and result in the loss of a large protein known as Lyst. The size and low abundance of this protein have impaired the detailed analysis of its function and how its absence leads to the dysfunction of lysosomes in CHS patients. We have established a simple model system to study the molecular function of Lyst and closely related proteins in the organism Dictyostelium discoideum. We have shown that the loss of a similar protein in this organism results in the same lysosomal defect. We are currently using the wide array of molecular tools available in this model system to dissect the function of Lyst-related proteins. We hope to use this as a starting point to understand better the human disease and design potential therapies. We are also interested in understanding how eukaryotic cells accomplish the last stage of the cell cycle: cytokinesis. We have identified several proteins important for cytokinesis and have generated knockout mutants lacking these proteins. We then analyze the phenotype of these mutants using a variety of cell biological techniques including imaging of GFP-labeled proteins. One of these proteins called LvsA plays a role in membrane traffic, while another called INCENP binds to chromosomes and microtubules.

Representative Publications:

Falkenstein, K., and De Lozanne, A. (2014) DictyosteliumLvsB has a regulatory role in endosomal vesicle fusion.  J. Cell Science 127:4356-4367.

Kypri, E., Falkenstein, K., and De Lozanne, A. (2013) Antagonistic control of lysosomal fusion by Rab14 and the Lyst-related protein LvsB. Traffic, 14: 599-609.

Wen, Y., Starvrou I., Bersuker, K., Brady R. J., De Lozanne, A., and O’Halloran, T.J. (2009) AP180- mediated trafficking of Vamp7B limits homotypic fusion of Dictyostelium contractile vacuoles. Mol. Biol. Cell, 20: 4278-4288

Du, F., Edwards, K., Shen, Z., Sun, B., De Lozanne, A., Briggs, S., & Firtel, R. A. (2008) Regulation of Contractile Vacuole Formation and Activity in Dictyostelium. EMBO Journal, 27: 2064-2076.

Li, H., Chen, Q., Kaller, M., Nellen, W., Gräf, R., & De Lozanne, A. (2008) Dictyostelium Aurora kinase has properties of both Aurora A and Aurora B kinases. Eukaryotic Cell, 7: 894-905.

Kypri, E., Schmauch, C., Maniak, M., and De Lozanne, A. (2007) The BEACH protein LvsB is localized on lysosomes and postlysosomes and limits their fusion with early endosomes. Traffic, 8: 774-783.

Chen, Q., Lakshmikanth, G. S., Spudich, J. A., and De Lozanne, A. (2007) Localization of DdINCENP at the cleavage furrow depends on Kif12, an MKLP1 homologue, and on its interaction with the actin cytoskeleton. Mol. Biol. Cell, 18: 3366-3374.

Chen, Q., Li, H. and De Lozanne, A. (2006) Contractile ring-independent localization of DdINCENP, a protein essential for spindle stability and cytokinesis. Mol. Biol. Cell, 17:779-788.

Wu, W., Yajnik, J., Siano, M., and De Lozanne, A. (2004) Structure-function analysis of the BEACH protein LvsA Traffic, 5:346-355.

De Lozanne, A. (2003) The role of BEACH proteins in Dictyostelium. Traffic, 4: 6-12

2004                            President’s Associates Teaching Excellence Award, University of Texas

2005                            College of Natural Sciences Teaching Excellence Award, U. of Texas

2006                            Jean Holloway Award for Excellence in Teaching, U. of Texas

2006                            Faculty Travel Award, U. of Texas

2008                            Inducted to the Academy of Distinguished Teachers, U. of Texas

2011                            Texas Blazers Faculty Excellence Award

2013                            Regents’ Outstanding Teaching Award

2014                            Natural Sciences Council Faculty Service Award

2015                            National Academies Education Fellow in the Life Sciences

2016                            Provost Teaching Fellow

2017                            Natural Sciences Council Faculty Service Award

BIO 320 - Cell Biology

BIO 325H - Honors Genetics

NSC 110H - Honors Seminar

UGS 303 - Originality in the Arts and Sciences