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Office: (859) 323-1455
Fax: (859) 257-8994
Lab: (859) 323-1649
Email: apierce@uky.edu
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Andrew J. Pierce, Ph.D.
Assistant Professor
Doctoral Studies: University of North Carolina at Chapel Hill.
Postdoctoral: Duke University and the Memorial Sloan-Kettering Cancer Center.
Research Statement:
The maintenance of genomic stability is of fundamental importance to cellular life. Although there are many ways in which this stability is challenged, DNA double-strand-breaks are particularly dire, as they threaten both the local information content at the site of the break as well as global chromosome structure. Fortunately, human cells have devised several mechanisms by which these lesions can be repaired, with varying consequences depending upon exactly which repair pathway is chosen. Using the tools of modern cellular biology and the techniques of molecular genetics, our research goal is to answer several fundamental questions such as: 1) How is the choice of repair pathway determined? 2) What are the components that underlie the machinery of the various repair mechanisms and what are the biochemical functions of these components? 3) Under which circumstances and by which methods can the choice of repair pathway and the outcome of repair be manipulated? Answers to these questions will have broad importance ranging from furthering knowledge of the basic science of cellular DNA metabolism, to clinical concerns such as maximizing the effectiveness of cancer treatment, and enabling practical gene therapies for human diseases at the molecular level.
More details can be found at the lab's web homepage (this is a non-University web site): http://www.paralog.com/ajp.
Selected Recent Publications:
Michael W. Killen, Dawn M. Stults, Noritaka Adachi, Les Hanakahi and Andrew J. Pierce. Loss of Bloom syndrome protein destabilizes human gene cluster architecture. Human Molecular Genetics (in press), 2009. PDF
Jasmina Kurepa, Songhu Wang, Yan Li, David Zaitlin, Andrew J. Pierce and Jan A. Smalle.
Loss of 26S proteasome function leads to increased cell size and decreased cell number in Arabidopsis shoot organs. Plant Physiology 150(1): 178-89, 2009. PDF
Dawn M. Stults, Michael W. Killen, Heather H. Pierce, Andrew J. Pierce. Genomic architecture and inheritance of human ribosomal RNA gene clusters. Genome Research 18(1): 13-18, 2008. PDF
Ranjit S. Bindra, Shannon L. Gibson, Alice Meng, Ulrica Westermark, Maria Jasin, Andrew J. Pierce, Robert G. Bristow, Marie K. Classon and Peter M. Glazer. Cancer Research 65(24): 11597-11604, 2005. PDF
Koji Nakanishi, Yun-Gui Yang, Andrew J. Pierce, Toshiyasu Taniguchi, Martin Digweed, Alan D. D’Andrea, Zhao-Qi Wang and Maria Jasin. Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair. Proceedings of the National Academy of Science 102(4): 1110-1115, 2005. PDF
Andrew J. Pierce and Maria Jasin. Measuring recombination proficiency in mouse embryonic stem cells. Methods in Molecular Biology 291:373-384, 2004. PDF
Jeremy M. Stark, Andrew J. Pierce, Jin Oh, Albert Pastink and Maria Jasin. Genetic steps of mammalian homologous repair with distinct mutagenic consequences. Molecular and Cellular Biology 24(21): 9305-9316, 2004. PDF
Felipe D. Araujo, Andrew J. Pierce, Jeremy M. Stark and Maria Jasin. Variant XRCC3 implicated in cancer is functional in homology-directed repair of double-strand breaks. Oncogene 21(26): 4176-80, 2002. PDF
Jeremy M. Stark, Peng Hu, Andrew J. Pierce, Mary Ellen Moynahan, Nathan Ellis, and Maria Jasin. ATP-hydrolysis by mammalian RAD51 has a key role during homology-directed DNA repair. Journal of Biological Chemistry 277(23): 20185-94, 2002. PDF
Claudia Wiese, Andrew J. Pierce, Stacey S. Gauny, Maria Jasin and Amy Kronenberg. Gene conversion is strongly induced in human cells by double-strand breaks and is modulated by the expression of BCL-xL. Cancer Research 62(5): 1279-1283, 2002. PDF
Andrew J. Pierce and Maria Jasin. NHEJ deficiency and disease. Molecular Cell 8(6): 1160-1161, 2001. PDF
Andrew J. Pierce, Peng Hu, Mingguang Han, Nathan Ellis and Maria Jasin. Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells. Genes and Development 15(24): 3237-3242, 2001. PDF
Artur Slupianek, Christoph Schmutte, Gregory Tombline, Malgorzata Nieborowska-Skorska, Grazyna Hoser, Michal O. Nowicki, Andrew J. Pierce, Richard Fishel and Tomasz Skorski. BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance. Molecular Cell 8(4): 795-806, 2001. PDF
Andrew J. Pierce, Jeremy M. Stark, Felipe D. Araujo, Mary Ellen Moynahan, Marianne Berwick and Maria Jasin. Double-strand breaks and tumorigenesis. Trends in Cell Biology 11(11): S52-59, 2001. PDF
Mary Ellen Moynahan, Andrew J. Pierce and Maria Jasin. BRCA2 is required for homology-directed repair of chromosomal breaks. Molecular Cell 7(2): 263-272, 2001. PDF
Andrew J. Pierce, Roger D. Johnson and Maria Jasin. XRCC3 promotes homology-directed repair of DNA damage in mammalian cells. Genes and Development 13(20): 2633-2638, 1999. PDF
Matthew J. Longley, Andrew J. Pierce and Paul Modrich. DNA Polymerase d is Required for Human Mismatch Repair in Vitro. Journal of Biological Chemistry 272(16): 10917-10921, 1997. PDF
Jane C. Azizkhan, David E. Jensen, Andrew J. Pierce, and Michael Wade. Transcription from TATA-less Promoters: Dihydrofolate Reductase as a Model. Critical Reviews in Eukaryotic Gene Expression 3(4): 229-254, 1993.
Andrew J. Pierce, Robert C. Jambou, David E. Jensen and Jane Clifford Azizkhan. A Conserved DNA Structural Control Element Modulates Transcription of a Mammalian Gene. Nucleic Acids Research 20(24): 6583-6587, 1992. PDF
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