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Faculty Detail    
Campus Address MCLM 684 Zip 0005
Phone  205-975-5449
Other websites

Medical School  University of Pecs, Medical School    1984  M.D. 
Residency  University of Pecs, Medical School and Haynal Imre University of Health Sciences Budapest, Hungary    1988  Pathologist, Histopathologist 

Pathology and Histopathology  1988 

Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Associate Professor
Center  Comprehensive Diabetes Center  Comprehensive Diabetes Center Associate Professor
Center  Cystic Fibrosis Research Center  Cystic Fibrosis Research Center Associate Professor
Center  GL Ctr for Craniofacial, Oral, & Dental Disorders  GL Ctr for Craniofacial, Oral, & Dental Disorders Associate Professor

Graduate Biomedical Sciences Affiliations
Cell, Molecular, & Developmental Biology 
Genetics, Genomics and Bioinformatics 
Medical Scientist Training Program 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Dr Bebok completed her medical degree and a residency program in Pathology and Histopathology at the University Medical School of Pecs, Hungary. As a student and later as faculty member, she worked under the guidance of Dr. Peter Nemeth at the Department of Immunology at the University Medical School of Pecs, Hungary. In 1993, she started a postdoctoral fellowship at the Department of Physiology, University of Alabama at Birmingham under the mentorship of Dr. Eric Sorscher. As junior faculty at the Department of Medicine at UAB, and associate scientist of the Cystic Fibrosis Research Center, she worked on the cellular and molecular mechanisms underlying cystic fibrosis. Dr. Bebok's research concentrates on cellular mechanisms that govern membrane protein biogenesis and how they contribute to the development of human disorders. She joined the Department of Cell Biology in 2002.

Research/Clinical Interest
Membrane protein expression regulation by the unfolded protein response (UPR) and mutations. The consequences of synonymous mutations on protein structure and function.
Our studies concentrate on 1) cellular mechanisms that reduce endoplasmic reticulum (ER) protein load during the unfolded protein response (UPR) to alleviate ER stress and 2) how mutations and single nucleotide polymorphism affect mRNA structure and co-translational protein folding. ER stress and activation of the UPR contribute to the pathogenesis of a wide range of human disorders including chronic obstructive pulmonary diseases (COPD), diabetes mellitus and neurodegenation. Thus, understanding the molecular pathways of the UPR will provide important clues for the development of molecular therapies. We are interested in genes that are repressed at the transcriptional and post-transcriptional levels by the UPR. We have shown that transcriptional repression, reduced translation and enhanced endoplasmic reticulum associated degradation (ERAD) contribute to decreased cystic fibrosis transmembrane conductance regulator (CFTR) function during ER stress. Reduced CFTR function and markers of UPR activity have been observed in patients with chronic bronchitis and COPD. To understand post-transcriptional gene repression during ER stress, we identified UPR induced miRNAs. We have shown that the UPR activated transcription factor XBP1, induces the expression of miR-346, defining a novel function for XBP1, and identified the targets of miR-346 as genes that regulate immune responses and ER peptide influx. We selected additional micro-RNAs that are regulated during the UPR and studies are in progress to define their ER stress associated regulators and understand their biological significance by characterizing their targets. Our second project investigates how mutations and synonymous single nucleotide polymorphisms (SNPs) affect mRNA structure and consequently, co-translational protein folding. We have demonstrated that one SNP in the CFTR gene alters mRNA structure and affects translation. We are investigating the functional consequences of this SNP and the role of other SNPs in CFTR folding. I have a strong background in pathology, immunology and for the past 15 years I studied membrane protein biogenesis in epithelial cells.

Selected Publications 
Publication PUBMEDID
Rab, A., R. Bartoszewski, A. Jurkuvenaite, J. Wakefield, J. F. Collawn, and Z. Bebok. 2007. Endoplasmic reticulum stress and the unfolded protein response regulate genomic cystic fibrosis transmembrane conductance regulator expression. Am J Physiol Cell Physiol 292:C756.  16987996 
Bartoszewski, R., Rab, A., Twitty, G., Stevenson, L., Fortenberry, J., Piotrowski, A., Dumanski, J., Bebok Zs. The mechanism of CFTR transcriptional repression during the unfolded protein response. J. Biol.Chem. 283:12154-65, 2008. PMID:18319256  18319256 
Bartoszewski, R, Rab A, Jurkuvenaite A, Mazur M, Collawn JF, and Bebok Z. Activation of the unfolded protein response by ΔF508 CFTR. Am J Respir Cell Mol Biol. 39: 448-57, 2008. PMID: 18458236  18458236 
Bartoszewski, R., Rab, A., Fu L., Collawn JF. and Bebok, Z. Methods to Study Membrane Protein Expression Regulation by the Unfolded Protein Response. Methods in Enzymology, UPR and Cellular Stress. Methods Enzymol. 2011;491:3-24. PMID: 21329791  21329791 
Bartoszewski, R., Brewer, J. W., Rab, A., Crossman, D. K., Bartoszewska, S., Kapoor, N., Fuller, C., Collawn, J. F., Bebok, Z. The unfolded protein response (UPR)-activated transcription factor XBP1 induces micro-RNA-346 expression that Targets the human antigen peptide transporter 1 (TAP1) mRNA and governs immune regulatory genes. J. Biol. Chem. 2011.DOI: 10.1074/jbc.M111.304956 22002058  22002058 
The silent codon change I507-ATC->ATT contributes to the severity of the ΔF508 CFTR channel dysfunction.  23907436 
Influenza virus M2 targets cystic fibrosis transmembrane conductance regulator for lysosomal degradation during viral infection.  25795456 
Decoding mechanisms by which silent codon changes influence protein biogenesis and function.  25817479 
Bartoszewski, R., Jablonsky, ZM., Stevenson, L., Dai, Q., Kappes, J., Collawn, J.F., and Bebok, Z. A synonymous single nucleotide polymorphism in ΔF508 CFTR alters the secondary structure of the mRNA and the expression of the mutant protein. J. Biol. Chem., 285:37, 28741-8, 2010. PMID: 2937902.   2937902 

membrane proteins, ER stress, UPR, SNP, mutation, CFTR, micro-RNA