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Faculty Detail    
Name ELIZABETH S SZTUL
 
Campus Address MCLM 668 Zip 0005
Phone 205-934-1465
E-mail esztul@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor
Secondary  Neurobiology  Neurobiology Professor
Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Professor
Center  Civitan International Research Center  Civitan International Research Center Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  Cystic Fibrosis Research Center  Cystic Fibrosis Research Center Professor
Center  Medicine  Nephrology Res & Trng Ctr Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Structural Biology 
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Medical Scientist Training Program 
Neuroscience 
Neuroscience Graduate Program 

Biographical Sketch 
Elizabeth S. Sztul obtained a M.Sc. (1979) in Plant Physiology from University of Maryland, studying chloroplast biogenesis. She continued her graduate studies in Cell Biology at Yale University School of Medicine, working on membrane trafficking pathways in the laboratory of Nobel Prize winner, Dr. George Palade, and was awarded a Ph.D in 1984. She continued training as a Postdoctoral Fellow of the American Cancer Society (1985-1989) in Human Genetics at Yale University School of Medicine, working on mitochondrial biogenesis in the laboratory of Dr. Leon Rosenberg. During her postdoctoral work at Yale, she was also a Visiting Scientist at the European Molecular Biology Laboratory in Heidelberg, Germany, in the laboratory of Dr. Kathryn Howell. She was appointed Assistant Professor of Molecular Biology at Princeton University (1989-1995), where she received the National Science Foundation Presidential Young Investigator Award. Dr. Sztul joined the faculty in the Department of Cell Biology at UAB as an Associate Professor in Fall of 1995. She is a member of the UAB Comprehensive Cancer Center and of the Fleming Cystic Fibrosis Center. She spent a sabbatical year (2000-01) at the Wellcome Center for Human Genetics in Oxford, United Kingdom, in the laboratory of Dr. Yvonne Jones. At the national level she has served or serves on Scientific Advisory Panels for the National Institute of Health, American Cancer Society, National Science Foundation and the American Heart Association.

Society Memberships
Organization Name Position Held Org Link
ASCB     

Research/Clinical Interest
Title
Membrane Traffic; Protein Degradation
Description
My research interests focus on the molecular mechanisms that regulate the delivery of proteins to their cellular sites of action. Many human diseases are caused by either the failed delivery of a specific protein to its appropriate cellular site, or by the premature degradation of a critical cellular component. For example, cystic fibrosis is caused by the inability of the CFTR protein to be delivered to the surface of cells, while certain cancers are linked to rapid degradation of the Ptc receptor. The first area of study is to understand how intracellular membrane traffic is controlled. More specifically, how do cells mediate the transport of crucial proteins to the correct site within the cell? In eukaryotic cells, proteins are sequentially transported from the site of synthesis in the endoplasmic reticulum (ER), through the Intermediate Compartment (IC) and the Golgi complex to the cell surface or to the endosomal/lysosomal system. We are developing a “virtual” time and space map of all the molecular events that occur during protein transport. We have cloned several key proteins that are required in protein transport, and are using biochemical, immunological, morphological, genetic, and molecular technologies to delineate their exact function. A detailed understanding of protein traffic at the molecular level is an essential step toward developing disease-specific therapies that correct the deficient step in protein transport that characterizes each disease. A related area of research in my laboratory is to understand the control of protein degradation. Newly synthesized proteins must fold correctly in the ER. If folding is inefficient or impossible, the protein is recognized by the ER quality control system, and is eliminated through proteasomal degradation. We have developed an in vivo system, using the genetically tractable yeast, Saccharomyces cerevisiae, to analyze how misfolded proteins are selected out of the ER and sorted for degradation. We have identified a multi-component sorting machinery in yeast that functions to sequester misfolded proteins into subdomains of the ER as a prelude for degradation. Our current focus is to identify a functionally and molecularly similar sorting system in mammalian cells. The ultimate goal of this project is to develop technology that will selectively slow down degradative sorting of clinically relevant proteins.

Selected Publications 
Publication PUBMEDID
Brandon E, Szul T, Alvarez C, Grabski R, Benjamin R, Kawai R, Sztul E.
On and Off Membrane Dynamics of the Endoplasmic Reticulum-Golgi Tethering Factor p115 In Vivo. Mol Biol Cell. 2006 Jul;17(7):2996-3008. Epub 2006 Apr 19.  
16624868 
Sztul E, Lupashin V. Role of tethering factors in secretory membrane traffic.
Am J Physiol Cell Physiol. 2006 Jan;290(1):C11-26. Review.  
16338975  
Fu L, Gao YS, Tousson A, Shah A, Chen TL, Vertel BM, Sztul E. Nuclear aggresomes form by fusion of PML-associated aggregates. Mol Biol Cell. 2005 Oct;16(10):4905-17. Epub 2005 Jul 29.   16055507 
Fu L, Gao YS, Sztul E. Transcriptional repression and cell death induced by nuclear aggregates of non-polyglutamine protein. Neurobiol Dis. 2005 Dec;20(3):656-65. Epub 2005 Jun 16.
 
15964198 
Szul T, Garcia-Mata R, Brandon E, Shestopal S, Alvarez C, Sztul E. Dissection of membrane dynamics of the ARF-guanine nucleotide exchange factor GBF1. Traffic. 2005 May;6(5):374-85.   15813748 
Hosaka T, Brooks CC, Presman E, Kim SK, Zhang Z, Breen M, Gross DN, Sztul E, Pilch PF. p115 Interacts with the GLUT4 vesicle protein, IRAP, and plays a critical role in insulin-stimulated GLUT4 translocation. Mol Biol Cell. 2005 Jun;16(6):2882-90. Epub 2005 Mar 30.   15800058  
Brandon E, Sztul E. h-ERES-y in ER-Golgi transport. Dev Cell. 2004 Jul;7(1):6-8. Review.   15239949 
Brandon E, Gao Y, Garcia-Mata R, Alvarez C, Sztul E. Membrane targeting of p115 phosphorylation mutants and their effects on Golgi integrity and secretory traffic. Eur J Cell Biol. 2003 Aug;82(8):411-20.   14533739 
Grabski R, Szul T, Sasaki T, Timpl R, Mayne R, Hicks B, Sztul E. Mutations in COCH that result in non-syndromic autosomal dominant deafness (DFNA9) affect matrix deposition of cochlin. Hum Genet. 2003 Oct;113(5):406-16. Epub 2003 Aug 20.   12928864 
Garcia-Mata R, Szul T, Alvarez C, Sztul E. ADP-ribosylation factor/COPI-dependent events at the endoplasmic reticulum-Golgi interface are regulated by the guanine nucleotide exchange factor GBF1. Mol Biol Cell. 2003 Jun;14(6):2250-61. Epub 2003 Apr 4.   12808027 
Alvarez C, Garcia-Mata R, Brandon E, Sztul E. COPI recruitment is modulated by a Rab1b-dependent mechanism. Mol Biol Cell. 2003 May;14(5):2116-27. Epub 2003 Feb 6.   12802079  
Garcia-Mata R, Sztul E. The membrane-tethering protein p115 interacts with GBF1, an ARF guanine-nucleotide-exchange factor. EMBO Rep. 2003 Mar;4(3):320-5.   12634853  
Garcia-Mata R, Sztul E. The membrane-tethering protein p115 interacts with GBF1, an ARF guanine-nucleotide-exchange factor. EMBO Rep. 2003 Mar;4(3):320-5.   12634853  
Fu L, Sztul E. Traffic-independent function of the Sar1p/COPII machinery in proteasomal sorting of the cystic fibrosis transmembrane conductance regulator. J Cell Biol. 2003 Jan 20;160(2):157-63. Epub 2003 Jan 21.   12538638 
Garcia-Mata, R., Gao, Y and E. Sztul. 2002. Hassles with taking out the garbage: aggravating aggresomes. Traffic, 3:388-396.  12010457 
Ito, H., K. Kamei, Y. Inaguma, R. Garcia-Mata, E. Sztul and K. Kanefusa. 2002. Inhibition of proteasomes induces accumulation, phosphorylation and recruitment of HSP27 and aB-crystallin to aggresomes. J. Biochem., 131:593-603.  11926998 
Alvarez, C and E.S. Sztul. 2001. The p115-interactive proteins GM130 and giantin participate in ER-Golgi transport. J. Biol. Chem. 276:2693-2700.  11035033 
Garcia-Mata, R., Y-S. Gao, C. Alvarez, and E.S. Sztul. 2000. The membrane transport factor p115 recycles only between homologous compartments in intact heterokaryons. Eur. J. Cell Biology 79:1-11.  10826491 
Linstedt, A., S.A. Jesch, T.H. Lee, R. Garcia-Mata, and E.S. Sztul. 2000. Binding relationships of membrane tethering components: the giantin N-terminus and the GM130 N-terminus compete for binding to the p115 C-terminus. J. Biol. Chem. 275:10196-10202.  10744704 
Sanchez, V., K. Gries, E. Sztul and W.J. Britt. 2000. Accumulation of virion tegument and envelope proteins in a stable cytoplasmic compartment during HCMV replication. Characterization of a potential site of Virus assembly. J. Virology 74:975-986.  10623760 
Alvarez, C., H. Fujita, H., Hubbard, A., and E.S. Sztul. 1999. ER to Golgi transport: requirement for p115 at a pre-Golgi VTC stage. J. Cell Biology 147:1-17.  10601335 
Garcia-Mata, R., Bebok, Z., Sorscher, E., and E.S. Sztul. 1999. Characterization and dynamics of aggresome formation by a non-ubiquitinated cytosolic GFP-chimera. J. Cell Biology 146:1239-1254  10491388 
Alvarez, C., and E.S. Sztul. 1999. Brefeldin A (BFA) disrupts the organization of the microtubule and the actin cytoskeletons. Eur. J. Cell Biology 78:1-14.  10082419 
Gao, Y and E. Sztul. Novel association of the Golgi complex with the IF cytoskeleton: interaction of the Golgi protein FTCD with vimentin IFs. 2001. J. Cell Biology, 152:877-94.  11238446 

Keywords
Cystic fibrosis, membrane traffic, degradation, quality control