Leland Stanford Junior University

Other

Mindy Tsai

Stephen J Galli

See-Ying Tam

Carolyn Ruth Bertozzi

Peter Robinson

Adrian Martin Piliponsky

Cheng-ting Tsai

Kaori Mukai

Methods and reagents for multiplex detection of antibodies are disclosed. In particular, the invention relates to multiplex detection of antibodies using antigen-DNA and antibody-binding agent-DNA conjugates carrying DNA barcodes for identifying and quantitating disease-relevant antibody isotypes, such as those involved in allergic responses, autoimmune diseases, infections, and inflammation.

Multiplex isotype-specific antibody detection

Sepsis is a complex, incompletely understood and often fatal disorder, typically accompanied by hypotension, that is considered to represent a dysregulated host response to an infection. Neurotensin (NT) is 13-amino-acid peptide that, among its multiple effects, induces hypotension. It is shown herein that plasma concentrations of NT are increased in humans with sepsis and in mice after caecal ligation and puncture (CLP), a model of sepsis. Mast cells can degrade NT through neurotensin receptor 1-and neurolysin-dependent mechanisms, diminishing the hypotensive effects of NT, reducing intraperitoneal NT concentrations, and improving survival. These findings show that mast cells can regulate NT concentrations, and identify NT as a biomarker and therapeutic target in sepsis.

Neurotensin as a marker and therapeutic target for sepsis

Non-human transgenic animal models and cells derived therefrom are provided for RabGEF1 function. RabGEF1 is a negative regulator of Fc&#x3b5;RI-dependent mast cell activation and T cell activation via the T cell receptor and a lack of RabGEF1 results in the development of skin inflammation in vivo. The mast cells derived from such animals exhibit enhanced Ras-mediated signaling and functional responses when activated through high affinity IgE receptors. These cells show significant potentiation of IgE and antigen-dependent secretion of 3 classes of mast cell mediators, providing a useful source of mast cells for screening assays. The animals and cells derived therefrom are also useful for screening biologically active agents that may modulate RabGEF1 function, including therapeutic agents for the treatment of skin disorders, such as eczema, psoriasis, and the like, or for the treatment of other mast cell-associated disorders, including allergic disorders, such as asthma and hay fever, and certain autoimmune disorders, such as rheumatoid arthritis and multiple sclerosis. Inhibiting RabGEF1 function may be useful in those conditions in which it is desirable to enhance T cell and/or mast cell function, such as in AIDS or other immune deficiency disorders.

In vivo models for rabGEF1-dependent signaling and functions

Novel gene, rin2, and encoded protein are disclosed which can inhibit the functional response induced by Ras-dependent signaling pathways are disclosed. Methods of inhibiting or enhancing Ras-dependent signaling and methods of treatment utilizing Rin2 are also disclosed.

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Palo Alto, CA, United States of America

Mindy Tsai