Student Directory

Kathryn Huber Keener

Class Year: M4

 

Department/Institute/Center(s):

  • M.D./Ph.D. Program

 

Contact Information:

 

Biographical Information:

Hometown: Hibbing, MN

 

Education:

Undergraduate Education:  BA/04 Physics/Saint Olaf College, MN

 

Research Interests:

Research Interest: Elucidating the molecular mechanisms of cancer cell survival during periods of cellular stress

Advisor: Jin-Ming Yang, PhD
Graduate Program: Pharmacology

Thesis: Alterations in Gene Expression as a Response of Cancer Cells to stresses

Description:

Cancer cells, both within solid tumors and circulatory systems, exist in surroundings that are subject to a variety of stresses, including metabolic and environmental stresses. Nonetheless, cancer cells survive and can even thrive under hostile conditions, such as hypoxia, nutrient deprivation, and therapeutic regimens. My research examines the impact of both internal and external stresses on cancer cell survival. The goal of my first project is to determine the influence of internal stresses on the protein synthesis inhibitor, eukaryotic elongation factor-2 kinase (eEF-2K), whose over-expression has previously been linked to cancer cell survival. Post-translational modification of translation machinery is important for its regulation and could be critical for survival of cancer cells encountering stress. Thus, the purpose of my study is to examine the regulation of eEF-2K during stress with a focus on the phosphorylation status and stability of EF-2 kinase protein in cancer cells. 

 

My second project is a large next-generation sequencing study on the transcriptome of tamoxifen (Tam) resistant breast cancer cells.  Resistance to Tam, a widely used antagonist of the estrogen receptor, is a common problem in breast cancer therapy, since one-third of patients treated with Tam have a recurrence of breast cancer.  The molecular mechanisms of Tam resistance are still not completely understood. My study examines the differential gene expression of both mRNA and small RNA in Tam-resistant breast cancer cells using a new analytical model.  Our study suggests that comparative analysis of transcriptomes has the potential to help identify new targets that can be exploited to modulate sensitivity of breast cancer cells to this clinically useful anti-estrogen agent.
Meeting Presentations
  • 2001
    Summer Research Symposium I & II, St. Olaf College, MN
    PEW Midstates Undergraduate Research Symposia in the Physical Sciences, Mathematics & Computer Science, University of Chicago, IL
  • 2002
    St. Olaf College Student Research Forum, Northfield, MN
    PEW Midstates Undergraduate Research Symposia in the Physical Sciences, Mathematics & Computer Science, Washington University
  • 2003
    St. Olaf College Student Research Forum, Northfield, MN
    Summer Research Symposium I & II, St. Olaf College, MN
  • 2004
    St. Olaf College Student Research Forum, Northfield, MN
  • 2010
    Penn State College of Medicine Graduate Research Forum, Hershey, PA
  • 2011
    Penn State College of Medicine Graduate Research Forum, Hershey, PA
    Association of Cancer Researchers Annual 102nd meeting, Orlando, FL

 

 

 

Publications:

Cederberg J, Nichol J, Frodermann E, Tollerud H, Hilk G, Buysman J, Kleiber W, Bongard M, Ward J, Huber K, Khanna T, Randolph J, Nitz D (2005) An anomaly in the isotopomer shift of the hyperfine spectrum of Lil J of Chem Physics 123(13):134321

 
Cederberg J, Frodermann E, Tollerud H, Huber K, Bongard M, Randolph J, Nitz D (2006) Nuclear electric quadrupole moments of Rb from the hyperfine spectrum of RbF"J of Chem Physics 124(24):244304

Huber-Keener KJ, Yang JM (2011) The impact of metabolic and therapeutic stresses on glioma progression and therapy.  In CC Chen (Ed.), Advances in the Biology, Imaging, and Therapies for Glioblastoma (pp.23-52). Rejeka, Croatia: Intech Open Access Publisher ISBN 979-953-307-197-7

Cheng Y, Zhang Y, Zhang L, Ren X, Huber-Keener KJ, Liu X, Zhou L, Liao J, Keihack H, Yan L, Rubin E, Yang JM (2012) MK-2206, a novel allosteric inhibitor of Akt, synergizes with gefitinib against malignant glioma via modulating both autophagy and apoptosis Mol Cancer Ther 11:154-164 PMID: 22057914

Zhang Y, Cheng Y, Zhang L, Ren X, Huber-Keener KJ, Lee S, Yun J, Wang HG, Yang JM (2011) Inhibition of eEF-2 kinase sensitizes human glioma cells to TRAIL and down-regulates Bci-xL expression Biochem Biophys Res Commun 414:129-134 PMID: 21945617

Huber-Keener KJ, Liu X, Wang Z, Freeman W, Wu S, Planas-Silva M, Ren X, Cheng Y, Zhang Y, Vrana K, Liu CG, Yang JM, Wu R (2012) Differential gene expression in tamoxifen-resistant breast cancer cells revealed by a new analytical model of RNA-Seq data PLoS One 9(7):e41333
 
Huber-Keener KJ, Evans BR, Ren X, Cheng Y, Hait WN, Yang JM (2012) Phosphorylation of elongation factor-2 kinase differentially regulates the enzyme's stability under stress conditions Biochem Biophys Res Commun 424(2):308-14
 
Cheng Y, SK UH, Zhang Y, Ren X, Zhang L, Huber-Keener KJ, Sun YW, Liao J, Amin S, Sharma AK, Yang JM (2012) Rational incorporation of selenium into temozolomide elicits superior antitumor activity associated with both apoptotic and autophagic cell death PLoS One 7(4):e35104
 
Zhang Y, Cheng Y, Ren X, Hori T, Huber-Keener KJ, Zhang L, Yap KL, Liu D, Shantz L, Qin ZH, Zhang S, Wang J, Wang HG, Shih IeM, Yang JM (2012) Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits tumor cell proliferation and oncogenesis Cancer Res 72(16): 4262-75
 
Cheng Y, Ren X, Zhang Y, Shan Y, Huber-Keener KJ, Zhang L, Kimball SR, Harvey H, Jefferson LS, Yang JM (2013) Integrated regulation of autophagy and apoptosis by EEF2K controls cellular fate and modulates the efficacy of curcumin and Velcade® against tumor cells Autophagy 9(2):208-10

 

 

 

Kathryn Huber Keener

 

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