Agnes Schonbrunn, Ph.D.
1975, Brandeis University
UT-Houston Medical School
Integrative Biology and Pharmacology
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Agnes Schonbrunn, Ph.D. 1975, Brandeis University UT-Houston Medical School |
Research Interests: Signal transduction; G protein coupled receptors; receptor regulation; neuroendocrine regulation.
The largest class of membrane receptors are members of the seven-transmembrane domain (7TMD), G protein-coupled (GPCR) receptor family and these receptors constitute the targets for most drugs. Our studies are aimed at understanding the mechanisms by which this receptor family responds to extracellular signals and the manner in which this responsiveness is regulated. We are especially interested in applying the knowledge and reagents we develop in our basic mechanistic investigations to clinical situations.
Our studies have focused on the receptors for the neuroendocrine peptide somatostatin which acts as an endocrine, paracrine and neuronal regulator. Five somatostatin receptor subtype genes (sst1 - sst5) have been cloned with each receptor subtype playing a unique physiological role. Our current studies are focused on the biochemical mechanisms involved in receptor regulation, with particular emphasis on the role of receptor phosphorylation in receptor desensitization and trafficking. Having found that different sst receptor subtypes are uniquely regulated, we have constructed and expressed receptor chimeras and phosphorylation defective receptor mutants to examine mechanisms involved in receptor desensitization and internalization. These studies have identified the biological importance of the phosphorylation sites in somatostatin receptors and are allowing us to investigate the molecular mechanisms controlling receptor phosphorylation and dephosphorylation. Somatostatin receptors are also present in a large number of cancers, in addition to normal neuronal and endocrine tissue. Thus, we have investigated the importance and role of different somatostatin receptor subtypes in a variety of tumors as well as in normal target tissues such as the brain, the pituitary and the pancreas. Further, since somatostatin analogs are in current clinical use for both the diagnosis and the treatment of a variety of cancers, we are examining the effects of a clinically used somatostatin analogs on different aspects of receptor function, including signaling and trafficking.
Students in the laboratory will be exposed to a variety of molecular, biochemical and immunocytochemical methods and will become familiar with the research in signal transduction, receptor function, and mechanisms of receptor regulation - areas which relate to the fields of molecular pharmacology, endocrinology, neuroscience and cancer.
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Cescato R, Schulz S, Waser B, Eltschinger V, Rivier JE, Wester HJ, Culler M, Ginj M, Liu Q, Schonbrunn A, Reubi JC (2006) Internalization of sst2, sst3 and sst5 receptors: Effects of somatostatin agonists and antagonists. Journal of Nuclear Medicine 47:502-511.
Liu Q, Cescato R, Dewi DA, Rivier J, Reubi JC, Schonbrunn A (2005) Receptor signaling and endocytosis are differentially regulated by somatostatin analogs. Molecular Pharmacology 68: 90-101.
Sarret P, Esdaile MJ, McPherson PS, Schonbrunn A, Kreienkamp H-J, Beaudet A (2004) Role of amphiphysin II in somatostatin receptor trafficking in neuroendocrine cells. J Biol Chem 279: 8029-8037.
Liu Q, Reubi JC, Wang Y, Knoll BJ, Schonbrunn A (2003) In vivo phosphorylation of the somatostatin 2A receptor in human tumors. J Clin Endocrinol Metab 88: 6073-6079.
Elberg G, Hipkin RW, Schonbrunn A (2002) Homologous and heterologous regulation of somatostatin receptor 2. Molecular Endocrinology 6: 2502-2514.
Program Affiliations:
Program in Cell and Regulatory
Biology (Pharmacology Track)
Program in Neuroscience