Kendall Blumer, PhD
Professor, Cell Biology and Physiology
Molecular Cell Biology Program
Washington University School of Medicine
Department of Ophthalmology and Visual Sciences
Campus Box 8096
660 S. Euclid Ave.
St. Louis, MO 63110
McDonnell Science 506
Signal transduction by G protein coupled receptors (GPCRs) in the cardiovascular, nervous and visual systems is the focus of our research. GPCRs are the largest and most important class of receptors in humans because they are the targets of more than half of all therapeutic agents, as well as many drugs of abuse. Our research focuses on RGS proteins, a large family we discovered that function as novel regulators, effectors and integrators in GPCR signaling pathways. Indeed, RGS proteins have important roles in hypertension, heart failure, anxiety, schizophrenia, vision and drug addiction. Accordingly, RGS proteins provide a promising new class of drug targets. Currently our goals are to elucidate the mechanistic and physiological functions of RGS proteins in the cardiovascular, nervous and visual systems through biochemical, cell biological, genetic and physiologic studies of knockout and transgenic mice. We are working to: 1) determine the mechanisms whereby RGS proteins participate in hypertension and heart failure; and 2) elucidate signaling functions of the RGS7 family in the visual and nervous systems. Both projects employ a multidisciplinary approach that includes biophysics (FRET, FLIM, FRAP), biochemistry, molecular biology, real-time imaging of signaling molecules, pharmacology, and mouse physiology. New students will have the opportunity to build on current projects or to develop novel research projects.
- Osei-Owusu P, Sabharwal R, Kaltenbronn KM, Rhee MH, Chapleau MW, Dietrich HH, Blumer KJ. Regulator of G protein signaling 2 deficiency causes endothelial dysfunction and impaired endothelium-derived hyperpolarizing factor-mediated relaxation by dysregulating Gi/o signaling. J Biol Chem. 2012 Feb 21. [Epub ahead of print]
- Jia L, Linder ME, Blumer KJ. Gi/o signaling and the palmitoyltransferase DHHC2 regulate palmitate cycling and shuttling of RGS7-family binding protein. J Biol Chem. 2011 286(15):13695-703.
- Chakir K, Zhu W, Tsang S, Woo AY, Yang D, Wang X, Zeng X, Rhee MH, Mende U, Koitabashi N, Takimoto E, Blumer KJ, Lakatta EG, Kass DA, Xiao RP. RGS2 is a primary terminator of β(2)-adrenergic receptor-mediated G(i) signaling. J Mol Cell Cardiol. 2011 50(6):1000-7.
- Dietrich HH, Abendschein DR, Moon SH, Nayeb-Hashemi N, Mancuso DJ, Jenkins CM, Kaltenbronn KM, Blumer KJ, Turk J, Gross RW. Genetic ablation of calcium-independent phospholipase A(2)beta causes hypercontractility and markedly attenuates endothelium-dependent relaxation to acetylcholine. Am J Physiol Heart Circ Physiol. 2010 298:H2208-20.
- Inoue-Mochita M, Inoue T, Epstein DL, Blumer KJ, Rao PV. RGS2-deficient mice exhibit decreased intraocular pressure and increased retinal ganglion cell survival. Mol Vis. 2009 15:495-504.
- Jayaraman M, Zhou H, Jia L, et al. R9AP and R7BP: traffic cops for the RGS7 family in phototransduction and neuronal GPCR signaling. Trends Pharmacol. Sci. 2009 30: 17-24.
- Grabowska, D, Jayaraman, M, Kaltenbronn, KM, et al. Postnatal induction and subcellular localization of R7BP, a membrane-targeting subunit for the RGS7 family and Gbeta5 in brain. Neuroscience 2008 151: 969-982.
- Gu S, Anton, A, Salim, S, et al. Alternative translation initiation of human RGS2 yields a set of functionally distinct proteins. Mol. Pharmacol. 2008 73: 1-11.
- Blumer KJ, Thorner J. An adrenaline (and gold?) rush for the GPCR community. ACS Chem. Biol. 2007 2(12) 783-786.
- Osei-Owusu P, Sun X, Drenan, et al. Regulation of RGS2 and second messenger signaling in vascular smooth muscle cells by cGMP-dependent protein kinase. J. Biol. Chem. 2007 282: 31656-65.