Kendall J. Blumer, Ph.D.

Professor
Cell Biology and Physiology

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

  • 314-362-1668

  • 314-362-1662

  • 314-362-7463

  • 506 McDonnell Medical Sciences Building

  • kblumer@wustl.edu

  • cancer, signal transduction, molecular pharmacology, autophagy, metabolism, drug development

  • Tumor cell biology, signal transduction, and drug development

Research Abstract:

Our research seeks to develop precision therapy for cancer and other diseases by identifying and exploiting abnormal signal transduction mechanisms, and developing pharmacological approaches to target them.

We currently study signal transduction by oncogenic GTPase-defective mutant G proteins of the Gq/11 class that occur in 5% of all human tumors and drive oncogenesis in ~90% of uveal melanoma (UM) patients. We focus mainly on UM because ~50% of patients develop metastatic disease that is rapidly and universally fatal due to lack of effective therapy. Our research has addressed this crucial, unmet clinical need by discovering that oncogenic Gq/11 can be inhibited in vitro and in vivo with a bioavailable inhibitor called FR900359 (FR). By probing UM cells with FR, we have discovered novel mechanisms whereby oncogenic Gq/11 signaling drives proliferation, invasion, metabolism and survival. Ongoing research is aimed at elucidating these novel mechanisms to target them and oncogenic Gq/11 in mouse models of metastatic UM and elict tumor regression. In parallel we are collaborating with synthetic organic chemists to develop methods of synthesizing FR in quantity sufficient for preclinical studies and clinical trials, and producing FR analogs for tumor-directed targeting and in vivo imaging of drug delivery and action.

The second major objective of our research is to develop a panel of FR-like molecules, each of which selectively targets different subclasses of G proteins in cancer or other diseases. Such inhibitors will reveal how G protein dysfunction causes disease, and provide novel lead compounds for therapeutic development. We are developing these inhibitors by combining computation chemistry, synthetic organic chemistry, and biophysical analyses of G protein structure and drug binding, with biochemical and cell-based studies of G protein function.

Mentorship and Commitment to Diversity Statement:
Our goal is for every lab member to thrive personally and scientifically. Good science and good community happen when we share.

We share our knowledge and skills and are open to questions. We help each other succeed and celebrate everyone's success.

We are serious about building an inclusive lab where people of all backgrounds are welcome.

We value our time outside and inside the lab. We take time to take care of ourselves and each other.

Selected Publications:

Complete list of our published work in MyBibliography:

https://www.ncbi.nlm.nih.gov/myncbi/kendall.blumer.1/bibliography/public/

Onken, MD, Noda, SE, Kaltenbronn, KM, Frankfater, C, Makepeace, CM, Fettig, N, Piggott, KD, Custer, PL, Ippolito, JE, Blumer, KJ. (2022) Oncogenic Gq/11 signaling acutely drives and chronically sustains metabolic reprogramming in uveal melanoma. J Biol Chem 298: 101495. PMC8761705.

Onken, MD, Blumer, KJ, and Cooper, JA. (2021) Uveal melanoma cells use ameboid and mesenchymal mechanisms of cell motility crossing the endothelium. Mol Biol Cell. 32, 413–421. PMC8098856

Onken, MD, Makepeace, CM, Kaltenbronn, KM, Choi, J, Hernandez-Aya, L, Weilbaecher, KN, Piggott, KD, Rao, PK, Yuede, CM, Dixon, AJ, Osei-Owusu, P, Cooper, JA, and Blumer, KJ. (2020) Targeting primary and metastatic uveal melanoma with a G protein inhibitor. J Biol Chem 296: 100403. PMC7948511 ***Editor’s Pick***

Truong A, Yoo JH, Scherzer MT, Sanchez JMS, Dale KJ, Kinsey CG, Richards JR, Shin D, Ghazi PC, Onken MD, Blumer KJ, Odelberg SJ, McMahon M. (2020) Clin Cancer Res. 26(23):6374-6386. doi: 10.1158/1078-0432.CCR-20-1675. Epub 2020 Sep 15. PMID: 32933997

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. Oct 5;7. pii: e38465.

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

Last Updated: 3/22/2022 2:19:22 PM

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.
Back To Top

Follow us: