Faculty
Oncology Division
Alphabetical list (active faculty):   
Amanda M. Smith

Amanda M. Smith, PhD

Instructor

Department of Medicine

Oncology Division

Stem Cell Biology

Research Interests

  • Mechanisms of leukemia initiation
  • Epigenetic states and the way they affect leukemia growth
  • Cancer genomics and mouse models

Contact

  • 314-362-8832 (office)
  • 314-362-9333 (fax)
  • Division of Oncology
    Campus Box 8007
    Washington University
    660 South Euclid Avenue
    St. Louis, MO 63110
  • Room 626 Southwest Tower (office)

Research

The focus of my work is the mechanism(s) of AML initiation specifically mediated by functional DNMT3A loss. Utilizing a number of different in vivo transgenic mouse models including DNMT3A null mice carrying wild-type human DNMT3A-cDNA and DNMT3A WT mice carrying the R882H human cDNA, both of which are under a Tet-on inducible promoter, we aim to investigate the role of hypomethylation in creating a pre-leukemic state. With cutting edge techniques including CRISPR/Cas9 mediated gene modification and next-generation sequencing techniques such as single cell RNAseq we will establish cooperating events that drive the pre-leukemic state to full-blown AML and determine whether reinstating DNMT3A enzymatic methyltransferase activity, and the subsequent DNA methylation marks, is sufficient at reducing and potentially eradicating AML. This work has profound clinical implications for the development of pharmacological strategies to eradicate founding AML clones that frequently harbor dominant-negative DNMT3A mutations.