University of Massachusetts

Harvard College

Other

Jon Goguen

Kyungae Lee

Egil Lien

Ning Pan

Sherman M Weissman

Yatindra Prashar

Peter E Newburger

Subrahmanyam V Yerramilli

The invention, in some aspects, relates to compounds and compositions useful for inhibiting Type III secretion systems in pathogenic bacteria, such as. In some aspects, the invention relates to methods for discovering inhibitors of the Type III secretion system and uses of such inhibitors in the treatment and prevention of disease.

Type III secretion inhibitors, analogs and uses thereof

Described herein are microorganisms that are modified so that they have an increased ability to be recognized by the innate immune system of a eukaryote, relative to an unmodified microorganism. A microorganism may be a gram-negative bacterium that has been modified to produce high potency lipopolysaccharide, e.g.,expressing LpxL. Such modified microorganisms may be used as vaccines for protection against an infection by the unmodified microorganism. They may also be used as delivery vehicles of one or more heterologous antigens, e.g., antigens from pathogens or those associated with a hyperproliferative eukaryotic cell.

Modified pathogens for use as vaccines

The present invention comprises a method to identify granulocytic cell genes that are differentially expressed upon exposure to a pathogen or in a sterile inflammatory disease by preparing a gene expression profile of a granulocytic cell population exposed to a pathogen or isolated from a subject having a sterile inflammatory disease and comparing that profile to a profile prepared from quiescent granulocytic cells. The present invention is particularly useful for identifying cytokine genes, genes encoding cell surface receptors and genes encoding intermediary signaling molecules. The invention also includes methods to identify a therapeutic agent that modulates the expression of at least one gene in a granulocytic population. Genes which are differentially expressed during neutrophil contact with a pathogen, such as a virulent bacteria, or that are differentially expressed in a subject having a sterile inflammatory disease are of particular importance.

Process to study changes in gene expression in granulocytic cells

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Holden, MA, United States of America

Jon Goguen