Wioletta Czaja, PhD

Healthy cooking, travel, nature and outdoor activities, skiing, hiking, photography

2006-2009 Member, Genetics Society of America

2007-present Member, Golden Key International Honor Society

2019-present Member, Masonic Cancer Center, University of Minnesota

2015-2019 Research Faculty, Biochemistry and Molecular Biology, University of Georgia, Athens, GA.

2013-2014 Postdoctoral training, Department of Animal Sciences, Washington State University, Pullman, WA.

2009-2013 Postdoctoral training, School of Molecular Biosciences, Washington State University, Pullman, WA.

2004-2009 Ph.D. Microbiology Molecular Biology and Biochemistry, University of Idaho, Moscow, ID.

2002-2004 M.S. Immunology and Virology, Maria-Curie Sklodowska University, Lublin, Poland.

2000-2002 B.S. Microbiology, Maria-Curie Sklodowska University, Lublin, Poland.

Nearly all forms of cancer contain significant levels of genomic instability (high frequency of mutations, chromosomal rearrangements), resulting from deficient or dysregulated DNA repair processes. The molecular events leading to genomic instability are not well understood. We investigate the fundamental mechanisms protecting genomic integrity, with a special focus on the epigenetic and chromatin-based regulation of DNA damage repair. We are also working on development of new approaches enabling direct detection, and genome-wide profiling of damaged and modified DNA bases, with the goal of uncovering novel mechanisms involved in mutagenesis and carcinogenesis. The long-term objective of our research is to understand how stability of the human genome is maintained and regulated in various cells and tissues, and to apply this new knowledge to promote advances in novel anti-cancer therapy and personalized medicine.We employ complementary approaches in biochemistry, cell and molecular biology, genetics and genomics using fungal model organisms (yeast-Saccharomyces cerevisiae) and human cell lines.

New tools in cancer risk identification and prevention; Development of new methodology ADA-SMRT enabling direct, genome-wide profiling of mutagenic alkyl DNA adducts. Alkyl DNA adducts are cytotoxic and mutagenic DNA lesions that arise from exposure of cells to numerous environmental carcinogens and cellular metabolites. Some of the most toxic alkyl DNA adducts are induced by commonly used anti-cancer drugs. DNA modifications induced by alkylating agents play significant roles in both the development and treatment of cancer. Persistent and inefficiently repaired alkyl DNA lesions can induce G→A transition mutations such as those often found in genes critical for malignant transformation, such as H-ras oncogene or TP53 tumor suppressor gene. DNA adducts induced by common alkylating agents predispose cells to malignant transformation. To understand how alkyl DNA adducts contribute to mutagenesis, cancer development and treatment, it is imperative to be able to examine complete, genome-wide profiles of these lesions and investigate how factors (such as modifications of chemotherapy agents, or the genomic and epigenomic landscape of the cell) influence initial adduct formation and repair. In collaboration with the University of Georgia, Athens, GA and Icahn School of Medicine, Mt. Sinai, New York, we are working on development of ADA-SMRT, a new methodology enabling direct detection of carcinogenic alkyl DNA adducts (ADA) by using SMRT DNA sequencing. The development of ADA-SMRT sequencing will enable, for the first time, direct and simultaneous high throughput mapping of various alkyl DNA adducts in eukaryotic genomes. This research will provide a framework for future investigation of the human genome and better understanding of the individual differences in cancer predisposition and response to chemotherapy.

Identification of new mechanisms of tumor suppression; Epigenetic (chromatin-based) regulation of DNA repair. DNA repair capacity vary considerably between individuals and between different tissues, highlighting involvement of genetic and epigenetic (chromatin-based) mechanisms in modulation of cellular toxicity to genotoxic agents. One of the major challenges in the DNA repair field is to understand how efficient DNA repair is accomplished in the context of highly compacted chromatin, which is inherently inhibitory to DNA repair processes. Our research in this area focuses on investigating the role of the chromatin remodeling factors in modulating the repair of the alkylated DNA damage via Base Excision Repair (BER). The Base Excision Repair (BER) is considered a fundamental tumor suppressor pathway in all cells, and is an attractive target in novel anti-cancer drug discovery. However, unlike other DNA repair pathways, the chromatin-based regulation of BER has been substantially understudied. In human cells, robust and tightly regulated BER is essential for the efficient repair of alkyl DNA adducts and protection of cells from the accumulation of mutations and malignant transformation. Dysregulation of the BER pathway (BER imbalance) is thought to drive carcinogenesis and contribute to chemoresistance. Previously we identified a link between the essential SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeler and the BER of alkyl DNA adducts in yeast cells. Currently we investigate the BER in human cancer cells deficient in the SWI/SNF. The human SWI/SNF remodeler is frequently mutated in 20% of cancers, raising the possibility that loss of SWI/SNF function might lead to aberrant, imbalanced BER in SWI/SNF-deficient cancers. These studies will elucidate new chromatin-based mechanisms that modulate the responses of the human cells to chemotherapy alkylating agents, and will provide new insights for improved therapy of SWI/SNF-deficient cancers.

• Exploratory Research Grant Award R21, NIEHS, NIH, University of Georgia, Athens, GA, 2018.
• Faculty Research Grant Award, University of Georgia, Athens, GA, 2015.
• Graduate and Professional Student (GPSA) Travel Award, University of Idaho, Moscow ID, 2009.
• Research Expo Award, University of Idaho, Moscow, ID, 2008.
• Research Excellence Award, Idaho INBRE/COBRE, Moscow, ID, 2007.
• Outstanding Academic Achievement Award, Gamma Sigma Delta, 2007.
• Outstanding Graduate Student, Maria-Curie Sklodowska University, Poland, 2004.
• Research Fellowship, University of Idaho, Moscow, ID, 2004.

1. Li Y., Mao P., Basenko EY., Lewis Z., Smerdon M., Czaja W^*. (2021) Versatile Cell-Based Assay for Measuring Base Excision Repair of DNA Alkylation Damage. (in BioRxiv)
2. Czaja, W., Bensasson, D., Bergman, C.M., Garfinkel, D.J. (2020) Evolution of Ty1 copy number control in yeast by horizontal transfer and recombination. PLoS Genet. 16(2): e1008632.
3. Czaja,W., Nakamura, Y., Eldridge J.A, Marquez Y., DeAvila D,M.,Thompson T.B., Rodgers B, D. (2019). Myostatin regulates pituitary development and hepatic IGF1. Am J Physiol Endocrinol Metabol, 316(6): E1036-E1049.
4. Hinz, J.M., Czaja W. (2015) Facilitation of Base Excision Repair by Chromatin Remodeling DNA Repair(Amst), 36:91-7.
5. Czaja,W., Mao,P. Smerdon,M.J.(2014) Chromatin remodeling complex RSC promotes Base Excision Repair in Saccharomyces cerevisiae. DNA Repair (Amst),16,35-43.
6. Czaja,W.,Miller,K.Y., Miller,B.L., Skinner, M.K. (2014) Structural and functional conservation of fungal MatA and human SRY sex determining transcription factors. Nature Communications. 17;5:5434.
7. Czaja, W., Miller, K.Y. and Miller, B.L. (2013) Novel Sexual-cycle Specific Gene Silencing in Aspergillus nidulans. Genetics 193(4):1149-62 (featured in the highlights of the month).
8. Czaja, W., Mao, P. and Smerdon, M.J. (2012) The Emerging Roles of ATP-Dependent Chromatin Remodeling Enzymes in Nucleotide Excision Repair. International journal of molecular sciences, 13, 11954-11973.
9. Czaja, K.C., Czaja, W.E. Giacobini-Robecchi,M.G.,Geuna,S., Fornaro,M. (2011) Injury-induced DNA replication and Neural Proliferation in the Adult Mammalian Nervous System. DNA replication and Related Cellular Processes, Kusic-Tisma, J. (ed.), ISBN: 978-953-307-775-8 InTech.
10. Czaja, W., Miller, K.Y. and Miller, B.L. (2011) Complex mechanisms regulate developmental expression of the matA (HMG) mating type gene in homothallic Aspergillus nidulans. Genetics, 189, 795-808.
11. Czaja, W., Bespalov, V.A., Hinz, J.M. and Smerdon, M.J. (2010) Proficient repair in chromatin remodeling defective ino80 mutants of Saccharomyces cerevisiae highlights replication defects as the main contributor to DNA damage sensitivity. DNA Repair (Amst), 9, 976-984.
12. Czaja (Pyrzak), W., Miller, K.Y. and Miller, B.L. (2008) Mating type protein Mat1-2 from asexual Aspergillus fumigatus drives sexual reproduction in fertile Aspergillus nidulans. Eukaryotic cell, 7, 1029-1040.