University of Minnesota
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Current Students

Pomeroy
Emily Pomeroy

E-mail:epomeroy@umn.edu

Thesis Advisor: Branden Moriarity

Year entered: 2016

Degrees received:
B.S., Northern Michigan University, Marquette, MI 2009
M.S., Northern Michigan University, Marquette, MI 2013

Thesis Research:

This natural function of killing tumor cells without the need for antigen specificity makes them an attractive cell type for cancer therapy.  NK cells have been used in clinical trials as a treatment for several cancer types, but success has been elusive due to lack of engraftment and inhibition of NK function by tumor cells.  Normal NK function is regulated at many levels to avoid autoimmunity, and tumors can take advantage of these systems to avoid being eliminated by NK cells. 

I am using CRISPR/Cas9 to genetically modify specific genes in human NK cells that regulate their ability to kill cancer cells.  Our lab has identified several target genes for modification in NK cells, which include PD-1, ADAM17, and CISH.  PD-1 is a negative regulator of NK cell function and its cognate receptor, PD-L1, is upregulated by many cancers.  ADAM17 mediates cleavage of CD16 on NK cells, and this effect negative regulates the ability of NK cells to perform antibody-dependent cell-mediated cytotoxicity (ADCC).  CISH is a recently-described intracellular negative regulator of NK cell activation and IL-15 signaling.  Deletion of CISH enhances NK cells proliferation, survival, and cytotoxicity towards tumors.  Importantly, CISH cannot be targeted by an antibody like other immune checkpoint proteins because it is an intracellular protein.  This makes it an attractive target for CRISPR/Cas9-based editing.  After knocking out our target genes, these enhanced NK cells will be used therapeutically in preclinical models of cancer. 

Publications:

  • Pomeroy EJ, Lee LA, Lee RD, Schirm DK, Temiz NA, Ma J, Gruber TA, Diaz-Flores E, Moriarity BS, Downing JR, Shannon KM, Largaespada DA, Eckfeldt CE. 2016. Ras oncogene-independent activation of RALB signaling is a targetable mechanism of escape from NRAS(V12) oncogene addiction in acute myeloid leukemia. Oncogene Dec 19.
  • Eckfeldt CE, Pomeroy EJ, Lee RD, Hazen KS, Lee LA, Moriarity BS, Largaespada DA. 2016. RALB provides critical survival signals downstream of Ras in acute myeloid leukemia. Oncotarget Oct 4.