Pillai E. Marinelli H. Fan P.taressrossregfe.ml
LPA receptor signaling: pharmacology, physiology, and pathophysiology
Nanjappan B. Song M. Cherkaoui I. Tardy S. Obtain biochemical validation of the ligand-binding pocket of S1P1 and S1P2 receptors derived from computational models using photoaffinity labeling and apply the model to in silico screening for S1P2- specific non-lipid leads with anti-metastatic activity.
Evaluate cyclic-phosphatidic acid and other LPA analogs, generated during the previous funding period, for inhibition of autotaxin, invasion, and metastasis in vitro and in vivo. This project continues as a highly-integrated, joint investigation between four senior and one junior investigator.
The proposed work built around the previous team that includes Drs. Tigyi molecular pharmacology, receptor biochemistry , Parrill computational modeling and Miller organic synthesis and will involve new collaborations with Dr. Baker junior faculty , who will assist with photoaffinity labels and mass spectrometry. Toggle navigation. Recent in Grantomics:.
Regulation of Stem Cell Pluripotency and Neural Differentiation by Lysophospholipids
Recently viewed grants:. Documented cellular effects of these lipid molecules encompass growth-factor-like influences on cells, including but not limited to survival, migration, adhesion differentiation, as well as pathophysiological actions associated with cancer. In turn, these cellular effects have roles in developing and adult organ systems such as the nervous system, cardiovascular system, reproductive system and, of relevance here, the immune system.
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The mechanisms for these actions can be attributed to a growing family of cognate, 7-transmembrane G protein-coupled receptors GPCRs , with documented validation through studies utilizing pharmacology, molecular genetics and an enlarging repertoire of chemical tools having agonist or antagonist properties. The growing literature on immunological effects of LP receptors, particularly those mediating the effects of S1P, has suggested possible therapeutic roles for this class of receptors. In particular, entry into humans of a non-selective S1P receptor agonist, FTY, for kidney transplantation and possibly other indications e.
Here we provide a brief introduction to receptor-mediated lysophospholipid signaling and discuss its basic and potential therapeutic roles in autoimmune-related diseases.
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Abstract: New therapies directed at ameliorating or altering autoimmune diseases represent an area of significant medical need.
Related Lysophospholipid Growth Factor Receptors
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