The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Microbiology and Molecular Genetics
Mechanisms of genome instability in budding yeast
Changes in genome can range from a single nucleotide sequence change to a chromosomal translocation and a whole chromosome loss. Such mutations and rearrangements are a prerequisite to evolution and also a pervasive feature of cancer development. Identifying key factors affecting genome stability is, therefore, central to understanding how a normal cell transforms into a malignant tumor.
My lab is interested in better understanding how DNA damages arise and how they are repaired in order to maintain genome integrity. We are using the simple eukaryotic model organism, Saccharomyces cerevisiae or budding yeast, to identify both external and endogenous factors leading to hypermutagenesis or hyper–recombination.
On-going projects include a study of how imbalance in the nucleotide composition is achieved and affects mutagenesis. Another genome instability-inducing factor under investigation is certain repetitive sequences containing runs of guanines. These sequence motifs potentially assemble into an unusual structure called G4 DNA. We are also studying the effect of chemotherapeutic drugs such as 5-Fluorouracil and Topoisomerase inhibitors on genome stability. While beneficial in killing cancer cells, these drugs can induce massive damages to DNA resulting in frequent mutations and rearrangements.
Students in my lab would gain experience in the fields of microbiology, yeast genetics and molecular biology, particularly of DNA. Manipulation of yeast genome using various techniques as well as selection and sequencing of mutants generated spontaneously or by treatment with chemotherapeutics and other agents will be a major part of the research in the lab.
Education & Training
Ph.D. - University of Chicago - 2000
Mechanisms of mutagenesis and chromosome rearrangements in S. cerevisiae