Honors & Awards

  • Postdoctoral Enrichment Award, Burroughs Wellcome Fund (2014-2017)
  • Tumor Biology Training Grant, NIH Institutional Grant/Stanford University (2013-current)
  • Dean's Postdoctoral Fellow, Stanford University (2013)

Professional Education

  • Bachelor of Science, University of Arkansas Fayetteville (2005)
  • Master of Science, University of Arkansas Fayetteville (2007)
  • Doctor of Philosophy, Ohio State University (2013)

Stanford Advisors

Journal Articles

  • Initiation of Genome Instability and Preneoplastic Processes through Loss of Fhit Expression PLOS GENETICS Saldivar, J. C., Miuma, S., Bene, J., Hosseini, S. A., Shibata, H., Sun, J., Wheeler, L. J., Mathews, C. K., Huebner, K. 2012; 8 (11)


    Genomic instability drives tumorigenesis, but how it is initiated in sporadic neoplasias is unknown. In early preneoplasias, alterations at chromosome fragile sites arise due to DNA replication stress. A frequent, perhaps earliest, genetic alteration in preneoplasias is deletion within the fragile FRA3B/FHIT locus, leading to loss of Fhit protein expression. Because common chromosome fragile sites are exquisitely sensitive to replication stress, it has been proposed that their clonal alterations in cancer cells are due to stress sensitivity rather than to a selective advantage imparted by loss of expression of fragile gene products. Here, we show in normal, transformed, and cancer-derived cell lines that Fhit-depletion causes replication stress-induced DNA double-strand breaks. Using DNA combing, we observed a defect in replication fork progression in Fhit-deficient cells that stemmed primarily from fork stalling and collapse. The likely mechanism for the role of Fhit in replication fork progression is through regulation of Thymidine kinase 1 expression and thymidine triphosphate pool levels; notably, restoration of nucleotide balance rescued DNA replication defects and suppressed DNA breakage in Fhit-deficient cells. Depletion of Fhit did not activate the DNA damage response nor cause cell cycle arrest, allowing continued cell proliferation and ongoing chromosomal instability. This finding was in accord with in vivo studies, as Fhit knockout mouse tissue showed no evidence of cell cycle arrest or senescence yet exhibited numerous somatic DNA copy number aberrations at replication stress-sensitive loci. Furthermore, cells established from Fhit knockout tissue showed rapid immortalization and selection of DNA deletions and amplifications, including amplification of the Mdm2 gene, suggesting that Fhit loss-induced genome instability facilitates transformation. We propose that loss of Fhit expression in precancerous lesions is the first step in the initiation of genomic instability, linking alterations at common fragile sites to the origin of genome instability.

    View details for DOI 10.1371/journal.pgen.1003077

    View details for Web of Science ID 000311891600058

    View details for PubMedID 23209436