Abstract: Methods are provided for decreasing demyelinating inflammatory disease in a subject by inhibiting the activity of chemokine-like receptor 1 (CMKLR1). Methods are also provided for screening for agents that find use in treating demyelinating inflammatory disease in a subject.

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: 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 an alternative embodiment, the agent is an antagonist that blocks CCR4 biological activity. An advantage of the invention is the selectivity for systemic memory T cells, without affecting native T cells or intestinal memory T cells.

Abstract: Clinical patient tissue samples are classified according to the physiological status of cells present in the sample. In some embodiments of the invention, such cells are classified according to their ability to respond to therapeutic agents and treatments. In other embodiments, the cells or tissue samples are classified according to their status with respect to the activity of pathways of interest. The information thus derived is useful in prognosis and diagnosis, and can further be used develop surrogate markers for disease states, and to investigate the effect of genetic polymorphisms in the responsiveness and state of cells involved in disease.

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: Clinical patient tissue samples are classified according to the physiological status of cells present in the sample. In some embodiments of the invention, such cells are classified according to their ability to respond to therapeutic agents and treatments. In other embodiments, the cells or tissue samples are classified according to their status with respect to the activity of pathways of interest. The information thus derived is useful in prognosis and diagnosis, and can further be used develop surrogate markers for disease states, and to investigate the effect of genetic polymorphisms in the responsiveness and state of cells involved in disease.

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 invention relates to the interaction of MEC with CCR3 and/or CCR10 and to agents (e.g., ligands, antibodies, antagonists, agonists, inhibitors, promoters) which alter said interaction. In one aspect, the invention relates to methods for detecting or identifying an agent (i.e., molecule or compound) which can modulate (inhibit, promote) the binding of MEC to CCR3 and/or CCR10. In another aspect, the invention relates to a method of treating a subject having an inflammatory condition, comprising administering to the subject an effective amount of an agent which modulates the binding of MEC to CCR3 and/or CCR10.

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: Methods and compositions are disclosed for the inhibition of cancer metastases mediated by endothelial adhesion molecules. The present invention discloses that sialyl Lea and di-sialyl Lea, which are expressed at the surface of cancer cells, function as a binding partner for LEC-CAMs, such as ELAM-1, which are expressed at the surface of endothelial cells. The present invention also discloses that LEC-CAMs, such as ELAM-1, involved in cancer metastasis share a carbohydrate domain common to both sialyl Lea and sialyl Lex. Antibodies, saccharides, glycoconjugates, enzyme inhibitors and other compounds may be used in the methods of the present invention to inhibit the binding of malignant cells to endothelial cells for a variety of purposes in vivo and in vitro.

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: Clinical patient tissue samples are classified according to the physiological status of cells present in the sample. In some embodiments of the invention, such cells are classified according to their ability to respond to therapeutic agents and treatments. In other embodiments, the cells or tissue samples are classified according to their status with respect to the activity of pathways of interest. The information thus derived is useful in prognosis and diagnosis, and can further be used develop surrogate markers for disease states, and to investigate the effect of genetic polymorphisms in the responsiveness and state of cells involved in disease.

Abstract: Methods and compositions are disclosed for the inhibition of cancer metastases mediated by endothelial adhesion molecules. The present invention discloses that sialyl Lea and di-sialyl Lea, which are expressed at the surface of cancer cells, function as a binding partner for LEC-CAMs, such as ELAM-1, which are expressed at the surface of endothelial cells. The present invention also discloses that LEC-CAMs, such as ELAM-1, involved in cancer metastasis share a carbohydrate domain common to both sialyl Lea and sialyl Lex. Antibodies, saccharides, glycoconjugates, enzyme inhibitors and other compounds may be used in the methods of the present invention to inhibit the binding of malignant cells to endothelial cells for a variety of purposes in vivo and in vitro.

Abstract: The invention relates to the interaction of MEC with CCR3 and/or CCR10 and to agents (e.g., ligands, antibodies, antagonists, agonists, inhibitors, promoters) which alter said interaction. In one aspect, the invention relates to methods for detecting or identifying an agent (i.e., molecule or compound) which can modulate (inhibit, promote) the binding of MEC to CCR3 and/or CCR10. In another aspect, the invention relates to a method of treating a subject having an inflammatory condition, comprising administering to the subject an effective amount of an agent which modulates the binding of MEC to CCR3 and/or CCR10.

Abstract: Novel methods and compositions are provided for modulating homing of leukocytes, particularly lympho-cytes, where the compounds are cross-reactive with Neu5Ac2-3Gal&bgr;1-X[Fuc&agr;1-y]GlcNAc, where one of x and y is three and the other is four. These compounds may be administered to a host associated with inflammation, to avoid the deleterious effects of leukocyte infiltration and for directing molecules to such sites.

Abstract: Novel methods and compositions are provided for modulating homing of leukocytes, particularly lymphocytes, where the compounds are cross-reactive with Neu5Ac2-3Gal&bgr;1−X[Fuc&agr;1−y]GlcNAc, where one of x and y is three and the other is four. These compounds may be administered to a host associated with inflammation, to avoid the deleterious effects of leukocyte infiltration.

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 CD45Ra31 , and integrin &agr;4&bgr;731 , 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.

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 &agr;4&bgr;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.

Abstract: Methods and compositions are disclosed for the inhibition of cancer metastases mediated by endothelial adhesion molecules. The present invention discloses that sialyl Le.sup.a and di-sialyl Le.sup.a, which are expressed at the surface of cancer cells, function as a binding partner for LEC-CAMs, such as ELAM-1, which are expressed at the surface of endothelial cells. The present invention also discloses that LEC-CAMs, such as ELAM-1, involved in cancer metastasis share a carbohydrate domain common to both sialyl Le.sup.a and sialyl Le.sup.x. Antibodies, saccharides, glycoconjugates, enzyme inhibitors and other compounds may be used in the methods of the present invention to inhibit the binding of malignant cells to endothelial cells for a variety of purposes in vivo and in vitro.