Vasquez, Karen M.

Vasquez, Karen M. Ph.D.

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Research Interests

DNA damage and repair, genomic instability, gene targeting, DNA structure, cancer therapeutics

Current Research

Our research efforts are focused in three general areas within an overall theme of genome instability, DNA damage and mechanisms of repair. A unique feature of our approach is an emphasis on the role of DNA structure, including non-canonical structures such as triplex DNA, as recognition sites for repair machinery, sources of genomic instability, and as a basis for technology to target DNA damage to specific genomic sites.

  1. DNA structure in genomic instability and human disease.
    The consequences of genomic instability are causative factors for several human diseases that involve repetitive DNA sequences. Many repetitive sequences are able to adopt non-B secondary structures. Interestingly, many of these repeats occur near breakpoints of chromosomal translocations, implicating them in cancer etiology. One example is the H-DNA-forming sequence in the human c-MYC gene that maps to breakage hotspots in Burkitt's lymphoma, that we have discovered is both mutagenic and induces DNA double-strand breaks in mammalian cells. These exciting results provide the first evidence that naturally occurring H-DNA structures are mutagenic; they also support a role for DNA structure in oncogenic translocations. Our studies will determine the mutagenic potential and mechanistic role of non-canonical DNA structures in human disease, with an emphasis on translocation-mediated cancers.
  2. Molecular mechanisms of DNA damage recognition and repair.
    Defects in DNA repair systems can lead to severe clinical disorders; for example, it is estimated that ~90% of human cancers result from improperly repaired DNA damage. Our work aims to elucidate the molecular basis of damage recognition in order to develop a better understanding of the mutagenic potential and cancer risks of different types of DNA lesions.
  3. Novel strategies to modify gene structure and function in living organisms.
    Defects in DNA repair systems can lead to severe clinical disorders; for example, it is estimated that ~90% of human cancers result from improperly repaired DNA damage. Our work aims to elucidate the molecular basis of damage recognition in order to develop a better understanding of the mutagenic potential and cancer risks of different types of DNA lesions.

Selected Publications

  1. Belotserkovskii BP, di Silva E, Tornaletti S, Wang G, Vasquez KM, Hanawalt PC. A triplex-forming sequence from the human c-Myc promoter interferes with DNA transcription, J Biol Chem, 282 (44), 32433-41, 2007
  2. Wang G, Vasquez KM. Z-DNA, an active element in the genome, Front Biosci, 12, 4424-38, 2007
  3. Wu Q, Gaddis SS, Macleod MC, Walborg EF, Thames HD, Digiovanni J, Vasquez KM. High-affinity triplex-forming oligonucleotide target sequences in mammalian genomes, Mol Carcinog, 46 (1), 15-23, 2007
  4. Christensen LA, Finch RA, Booker AJ, Vasquez KM. Targeting oncogenes to improve breast cancer chemotherapy, Cancer Res, 66 (8), 4089-94, 2006
  5. Gaddis SS, Wu Q, Thames HD, Digiovanni J, Walborg EF, Macleod MC, Vasquez KM. A web-based search engine for triplex-forming oligonucleotide target sequences, Oligonucleotides, 16 (2), 196-201, 2006
  6. Wang G, Christensen LA, Vasquez KM. Z-DNA-forming sequences generate large-scale deletions in mammalian cells, Proc Natl Acad Sci U S A, 103 (8), 2677-82, 2006
  7. Reddy MC, Christensen J, Vasquez KM. Interplay between human high mobility group protein 1 and replication protein A on psoralen-cross-linked DNA, Biochemistry, 44 (11), 4188-4195, 2005
  8. Thoma BS, Wakasugi M, Christensen J, Reddy MC, Vasquez KM. Human XPC-hHR23B interacts with XPA-RPA in the recognition of triplex-directed psoralen DNA interstrand crosslinks, Nucleic Acids Res, 33 (9), 2993-3001, 2005
  9. Wu Q, Christensen LA, Legerski RJ, Vasquez KM. Mismatch repair participates in error-free processing of DNA interstrand crosslinks in human cells, EMBO Rep, 6 (6), 551-7, 2005
  10. Wang G, Vasquez KM. Naturally occurring H-DNA-forming sequences are mutagenic in mammalian cells, Proc Natl Acad Sci U S A, 101 (37), 13448-53, 2004

Contact Information


Mailing Address: P.O. Box 389, Smithville, Texas 78957
Physical Address: 1808 Park Road 1C, Smithville, Texas 78957
Phone: (512) 237-9525