Susan Rathe

E-mail: rath0096@umn.edu

Year entered: 2007

Degrees received:
B.S., Genetics, Cell Biology and Development, University of Minnesota, 2006
B.S., Biochemistry, University of Minnesota, 2007

Thesis research:
Acute myeloid leukemia (AML) strikes 12,000 people in the United States each year. Most patients will initially respond well to chemotherapy, but of those the majority will relapse with a drug resistant form of the disease. We are investigating the phenomenon of drug resistance to cytosine arabinoside (AraC), a key component of AML chemotherapeutic cocktails. AraC is a cytosine analog that interferes with DNA replication in growing cells. Computer analysis of gene expression data comparing drug sensitive cells to drug resistant cell lines developed in vitro has suggested a number of potential mechanisms that are associated with AraC drug resistance. Biochemical analyses indicate the drug resistant phenotype presented by these cells is specific to AraC and not a multidrug resistant phenotype. Future work involves: (1) biochemical assays to validate the mechanisms identified, (2) microarray analysis of drug sensitive and drug resistant cells derived from an in vivo mouse model to determine if the in vitro results are relevant and (3) comparisons to human AML expression studies to determine if the mouse model is relevant to human disease. Our initial goal is to establish a mouse model for AraC drug resistance that will mirror human chemotherapy resistance. Our ultimate goal is to identify companion drugs to AraC that will prevent the induction of an AraC resistant phenotype.

Publications:
Yin B, Tsai ML, Hasz DE, Rathe SK, Le Beau MM, Largaespada DA. 2007. A
microarray study of altered gene expression after cytarabine resistance in
acute myeloid leukemia. Leukemia. 21(5):1093-7.