Abstract: A method of screening biologically active agent based on the analysis of complex biological responses in culture. Methods for selecting cells and culture conditions for such screens are provided, as well as the identification of an optimized set of discrete parameters to be measured, and the use of biomap analysis for rapid identification and characterization of drug candidates, genetic sequences acting pathways, and the like. A feature of the invention is simultaneous screening of a large number of cellular pathways, and the rapid identification of compounds that cause cellular responses.

Abstract: The involvement of an expression product in a cell in a pathway is determined by genetically modifying the cell, incubating the cell with predetermined factors in induce a physiological state and measuring parameters affected by the pathway. Changes in the levels of the parameters as a result of the presence of the expressed product indicate that the expression product is involved with the pathway.

Abstract: A method of screening biologically active agent based on the analysis of complex biological responses in culture. Methods for selecting cells and culture conditions for such screens are provided, as well as the identification of an optimized set of discrete parameters to be measured, and the use of biomap analysis for rapid identification and characterization of drug candidates, genetic sequences acting pathways, and the like. A feature of the invention is simultaneous screening of a large number of cellular pathways, and the rapid identification of compounds that cause cellular responses.

Abstract: Methods are provided for the prevention and treatment of seizures and epilepsy. It is shown herein that leukocyte recruitment plays a key role in the pathogenesis of epilepsy. Treatment with an agent that inhibits leukocyte recruitment has therapeutic and preventative effects in blocking recurrent seizures and epilepsy.

Abstract: Methods are provided for regulating adipogenesis and metabolic function in adipocytes by modulating the activity of chemokine-like receptor 1 (CMKLR1). Exemplary agents include those that modulate binding of CMKLR1 to a cognate ligand (e.g., chemerin), those that modulate signaling from CMKLR1, and those that modulate expression of either CMKLR1 or its cognate ligand in target cells. Methods are also provided for screening for agents that find use in regulating fat accumulation in a subject.

Abstract: RhoA mediated signaling pathways are manipulated with specific domains of the RhoA protein that are translocation modified by conjugation or fusion to a transport domain. The compounds find use in therapeutic and research methods where it is desirable to selectively inhibit RhoA.

Abstract: Methods are provided to modulate the trafficking of leukocytes through interactions with one or more of a class of chemoattractant proteins having a cystatin-like structure. Exemplary of proteins in this class is chemerin, which interacts with the receptor CMKLR1. The chemoattractant polypeptide, or agonists of the chemoattractant receptor, act to concentrate responding leukocytes at a site of interest. Agonists and antagonists of the chemoattractant modulate immune responsiveness.

Abstract: Methods are provided to specifically modulate the trafficking of systemic memory T cells, particularly CD4+ T cells, without affecting naive T cells or intestinal memory T cells. It is shown that systemic memory T cells, which are characterized as CD45Ra?, and integrin ?4?7?, express high levels of CCR4. Ligands of CCR4, such as TARC or MDC, act as an adhesion trigger, wherein upon CCR4 binding, these cells undergo integrin-dependent arrest to the appropriate vascular receptor(s). This arrest acts to localize the cells at the target site. The methods of the invention manipulate this triggering, and CCR4 mediated chemotaxis, to affect the localization of T cells in targeted tissues. In one embodiment of the invention, the active agent is a CCR4 agonist, that acts to enhance T cell localization. In an alternative embodiment, the agent is an antagonist that blocks CCR4 biological activity.