Kendall J. Blumer, Ph.D.

Professor
Cell Biology and Physiology

Molecular Cell Biology Program
Biochemistry, Biophysics, and Structural Biology Program
Neurosciences Program

  • 314-362-1668

  • 314-362-1662

  • 314-362-7463

  • 8228

  • 506 McDonnell Medical Sciences Building

  • kblumer@wustl.edu

  • cancer, drug development, signal transduction

  • Tumor cell signal transduction and drug development

Research Abstract:

Our research currently focuses on uveal melanoma (UM), the most common ocular tumor in adults. Nearly half of UM patients develop metastatic disease, with mean survival of less than one year. Effective therapy is lacking. New therapeutic options are desperately needed.

Toward this goal, we have identified a bioavailable inhibitor that directly targets the oncogenic drivers in ~90% of UM tumors: constitutively active forms of the Gq/11 class of G protein alpha-subunits. We also discovered that signaling by these mutant G proteins targets epigenetic silencing to promote tumor formation.

Based on these discoveries, our goals are to determine: 1) how this inhibitor targets mutant G protein alpha-subunits; 2) whether this inhibitor is efficacious in mouse models of UM and patient-derived tumor samples; 3) whether we can produce synthetic analogs of this inhibitor for targeted therapy; and 4) whether components of the signaling mechanism that regulates epigenetic silencing could provide novel drug targets in UM.

Our research employs multidisciplinary approaches including biophysics, computational modeling, biochemistry, synthetic organic chemistry, molecular biology, imaging, pharmacology, and mouse models of cancer.

Selected Publications:

Sun, X., Sing, S., Blumer, K.J., and Bowman, G.R. (2018). Simulation of spontaneous G protein activation reveals a new intermediate driving GDP unbinding. eLife. submitted.

Onken, M.D., Makepeace, C.M., Kaltenbronn, K.M., Kanai, S.M., Todd, T.D., Wang, S., Broekelmann, T.J., Rao, P.K., Cooper, J.A., Blumer, K.J. (2018). Targeting nucleotide exchange to inhibit constitutively active G protein alpha-subunits in cancer cells. Sci Signaling. 11: eaao6852
http://stke.sciencemag.org/content/11/546/eaao6852

Scherer, S, Cain, MD, Kanai, SM, Kaltenbronn, KM, Blumer, KJ. (2017). Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and Galpha13. J Biol Chem. 292: 9906-18

Kanai, SM, Edwards, AJ, Rurik, JG, Blumer, KJ. (2017). Proteolytic degradation of regulator of G protein signaling 2 facilitates temporal regulation of Gq/11 signaling and vascular contraction. J Biol Chem. 292: 19266-78.

Rensing, D.T., Uppal, S., Blumer, K.J., & Moeller K.D. (2015). Toward the Selective Inhibition of G Proteins: Total Synthesis of a Simplified YM-254890 Analog. Org Lett. 17(9):2270-3


Last Updated: 9/10/2018 9:58:38 AM

Uveal melanoma, the large green mass pictured, is a cancer of the eye that has no targeted therapies. Research from the Blumer lab shows that a natural plant compound shuts down uveal melanoma cell growth in human tumor cells.
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