Leland Stanford Junior University

Other

Bioseek, Inc.

The United States Government As Represented by the Department of Veterans Affairs

Millennium Pharmaceuticals Limited

Discoverx Corporation

Eurofins Discoverx Corporation

Fabene, Paolo

Constantin, Gabriela

Asterand Acquisition LLC

Eugene C Butcher

Ellen L Berg

Jennifer Melrose

John L Magnani

Brian A Zabel

Paolo Francesco Fabene

Gabriela Constantin

Kareem Graham

Ivan Plavec

Lijun Wu

James Rottman

James J Campbell

James Campbell

Louis J Picker

Eric J Kunkel

Jian Zhang

Leslie M McEvoy

Dulce Soler-Ferr&aacute;n

Russell K Pachynski

Junliang Pan

Justin Monnier

James B Rottman

Philip R Streeter

Husein Hadeiba

Paolo Fabene

Methods are provided for treating autoimmune disease in a subject by inhibiting the activity of DGAT1.

DGAT1 inhibition for treatment of demyelinating inflammatory disease

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.

Function homology screening

Chemerin is a chemoattractant that selectively directs intra-tumor recruitment of CMKLR1+ cells. Blockade of CCRL2 from binding to chemerin in non-neoplastic tumor cells, e.g. peri-tumor stromal and/or hematopoietic cells allows for redistribution of chemerin into the tumor and enhanced responsiveness against a tumor.

Methods of enhancing anti-tumor immunity by administering antibodies to the CCRL2 chemerin receptor

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.

Anti-leukocyte recruitment therapy for the treatment of seizures and epilepsy

Compounds and methods are provided for decreasing demyelinating inflammatory disease in a subject by inhibiting the activity of chemokine-like receptor 1 (CMKLR1). In some embodiments such methods include treating demyelinating inflammatory disease in a subject by administering an agent that antagonizes the activity of chemokine-like receptor 1 (CMKLR1) and/or a CMKLR1 ligand (e.g., chemerin or other endogenous CMKLR1 ligands). Candidate compounds include, without limitation, analogs and variants of 2-(alpha-naphthoyl)ethyltrimethylammonium iodide.

Small molecule CMKLR1 antagonists in demyelinating disease

Tolerogenic populations of dendritic cells are provided, where the dendritic cells are characterized by expression of select tissue-specific homing receptors including the chemokine receptors CCR9; or CMKLR1; or the integrin CD103. The dendritic cells may be conventional/myeloid or plasmacytoid dendritic cells. The cells may be isolated from lymphoid tissue, from blood, or from in vitro culture, e.g. bone marrow culture, etc. Methods are provided for their identification, isolation and targeting in immunotherapeutic interventions in suppressing inflammatory disorders including autoimmunity, transplantation responses and allergic diseases. In some embodiments dendritic cell populations are fixed to render them immunosuppressive, thus allowing the cells to be typed and banked for future use.

Tolerogenic populations of dendritic cells

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.

Target for regulating multiple sclerosis

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.

Patient classification

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.

BioMAP analysis

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 &#x3b1;4&#x3b2;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.

Modulation of systemic memory T cell trafficking

Growing community of inventors

Portola Valley, CA, United States of America

Eugene C Butcher