Rodney E. Kellems, Ph.D.
Professor and Chairman


Description of Research

ANGIOTENSIN RECEPTORS, AUTOANTIBODIES, & DISEASE

Angiotensin receptor activating autoantibodies and preeclampsia.
Preeclampsia is the leading cause of death due to pregnancy with clinical consequences involving severe life-threatening vascular abnormalities. The molecular mechanisms responsible for the pathogenesis of preeclampsia remain poorly understood. We found that women with preeclampsia harbor autoantibodies capable of activating the angiotensin receptor, AT1R. We showed that these autoantibodies bind to a specific seven amino acid sequence on the second extracellular loop of the angiotensin receptor. Overall, our results provide strong evidence that these autoantibodies activate AT1 receptors on a variety of cells and thereby contribute to many features of the disease. Research is underway to determine the immunological origin of these autoantibodies and the mechanism by which they activate the AT1 receptor. This project is being carried out in collaboration with Dr. Yang Xia.

faculty-rodney-kellems-fig2

Angiotensin receptor activating autoantibodies (AT1-AAs) may underlie many features of preeclampsia. AT1-AAs from preeclamptic patients activate angiotensin receptors (AT1R) on the surface of many cell types and may be responsible for many features of this serious pregnancy disorder. We have shown that antibody-induced receptor activation results in the mobilization of intracellular calcium and the activation of many genes. We propose that AT1-AAs activate AT1 receptors by promoting receptor homodimerization. ROS, reactive oxygen species. SMC, smooth muscle cells; EC, endothelial cells.

Contact Information

Rodney.E.Kellems@uth.tmc.edu

UTHealth Medical School
Department of Biochemistry and Molecular Biology
6431 Fannin Street, MSB 6.200
Houston, Texas 77030

713-500-6124  Direct  713-500-0652 Fax

Education

Ph.D. - Princeton University

Postdoctoral Fellow - Stanford University

Research Interests

Receptor Activating Autoantibodies and Disease

Publications

Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice.

Zhou CC, Zhang Y, Irani RA, Zhang H, Mi T, Popek EJ, Hicks MJ, Ramin SM, Kellems RE, Xia Y.

Nat Med. 2008 Aug;14(8):855-62. doi: 10.1038/nm.1856. Epub 2008 Jul 27.

PMID: 18660815

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Receptor-activating autoantibodies and disease: preeclampsia and beyond.

Xia Y, Kellems RE.

Expert Rev Clin Immunol. 2011 Sep;7(5):659-74. doi: 10.1586/eci.11.56. Review.

PMID: 21895478

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Angiotensin receptor agonistic autoantibodies and hypertension: preeclampsia and beyond.

Xia Y, Kellems RE.

Circ Res. 2013 Jun 21;113(1):78-87. doi: 10.1161/CIRCRESAHA.113.300752.

PMID: 23788505

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Elevated sphingosine-1-phosphate promotes sickling and sickle cell disease progression

Zhang Y, Berka V, Song A, Sun K, Wang W, Zhang W, Ning C, Li C, Zhang Q, Bogdanov M, Alexander DC, Milburn MV, Ahmed MH, Lin H, Idowu M, Zhang J, Kato GJ, Abdulmalik OY, Zhang W, Dowhan W, Kellems RE, Zhang P, Jin J, Safo M, Tsai AL, Juneja HS, Xia Y

J Clin Invest. 2014 Jun 2;124(6):2750-61. doi: 10.1172/JCI74604. Epub 2014 May 16

PMCID:  PMC4089467

 

 

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