Leland Stanford Junior University

Applied Genomics, Inc.

Patrick O Brown

Tidhar Dari Shalon

Julie Sneddon

David Botstein

Mark M Davis

Charles M Perou

Daniel Lewis Kraft

Douglas T Ross

Sue Klapholz

Brian Z Ring

Anthony Oro

Howard Yuan-Hao Chang

Daniel Shin-Yu Chen

Stanley Nelson

Jan Matthijs Van De Rijn

Rob Seitz

Yoav Soen

Hanson Zhen

The present invention relates to the use of proteins that are differentially expressed in tumor associated stromal cells, as compared to normal stromal, as biomolecular targets for tumor treatment therapies. The present invention also provides compounds and pharmaceutically acceptable compositions for administration in the methods of the invention.

Bone morphogenetic protein antagonist and uses thereof

Methods are provided for classification of cancers by the expression of a set of genes referred to as the core serum response (CSR), or a subset thereof. The expression pattern of the CSR in normal tissues correlates with that seen in quiescent fibroblasts cultured in the absence of serum, while cancer tissues can be classified as having a quiescent or induced CSR signature. Patients with the induced CSR signature have a higher probability of metastasis. Classification according to CSR signature allows optimization of treatment, and determination of whether on whether to proceed with a specific therapy, and how to optimize dose, choice of treatment, and the like.

Gene expression signature for prediction of human cancer progression

T cells are profiled with respect to their expression of antigen receptor. The cells are arrayed on a planar or three-dimensional substrate through binding to immobilized or partially diffused MHC-antigen complexes. The cells may further be characterized with respect to their ability to respond to external stimulus in the microenvironment. External stimuli include cell-cell interactions, response to factors, and the like.

MHC-antigen arrays for detection and characterization of immune responses

A method and device for detecting or monitoring the treatment status of a selected physiological state or disease condition. The device has a subarray of genes which show a statistically significant change in gene level expression when compared with the control expression levels for that gene. The method involves applying a reporter-labeled messenger nucleic acid fraction to the array in the device, and comparing the pattern of gene expression on the array with that produced by labeled messenger nucleic acid from control cells. Also disclosed is a method of constructing the array.

Methods for constructing subarrays and subarrays made thereby

Microarrays of polypeptides on a solid support are provided. The microarray compositions find use in the multiplexed detection and quantitation of ligands, e.g. antigens or antibodies, in a miniaturized format. The substrate is used for detecting binding of ligands to a plurality of polypeptides for screening and diagnostic purposes.

Microarrays of polypeptides

A method of determining the relative amounts of individual polynucleotides in a complex mixture of different-sequence polynucleotides is disclosed. The polynucleotides, after fluorescent labeling, are contacted under hybridization conditions with an array of different DNA sequences disposed at discrete locations on a non-porous surface, at an array density of at least about 100 sequences/cm, where the different DNA sequences in the array are effective to hybridize to individual polynucleotides in the mixture. The level of fluorescence associated with each array sequence provides a measure of its relative amount in the mixture.

Substrates comprising polynucleotide microarrays

A method and device for detecting or monitoring the treatment status of a selected physiological state or disease condition. The device has a subarray of genes which show a statistically significant change in gene expression level when compared with the control expression levels for that gene. The method involves applying a reporter-labeled messenger nucleic acid fraction to the array in the device, and comparing the pattern of gene expression on the array with that produced by labeled messenger nucleic acid from control cells. Also disclosed is a method of constructing the array.

Method for analyzing gene expression patterns

Microarray for determining the relative abundances of polynuceotide sequences

The invention provides a variety of reagents for use in the diagnosis and management of breast cancer. The invention utilizes cDNA microarray technology to identify genes whose expression profile across a large group of tumor samples correlates with that of cytokeratin 5 and cytokeratin 17, markers for basal cells of the normal mammary lactation gland. The invention demonstrates that tumors that express cytokeratin 5/6 and/or 17 have a poor prognosis relative to tumors overall. The invention provides basal marker genes and their expression products and uses of these genes for diagnosis of breast cancer and for identification of therapies for breast cancer. In particular, the invention provides basal marker genes including cadherin3, matrix metalloproteinase 14, and cadherin EGF LAG seven-pass G-type receptor 2. The invention provides antibodies to the polypeptides expressed by these genes and methods of use thereof.

Methods of classifying, diagnosing, stratifying and treating cancer patients and their tumors

A method and apparatus for forming microarrays of biological samples on a support are disclosed. The method involves dispensing a known volume of a reagent at each selected array position, by tapping a capillary dispenser on the support under conditions effective to draw a defined volume of liquid onto the support. The apparatus is designed to produce a microarray of such regions in an automated fashion.

Methods for fabricating microarrays of biological samples

Functional analysis of genes is provided by employing insertional mutagenesis to a population of DNA molecules containing the gene of interest. The DNA is subjected to a degree of insertion, where the total population of molecules provides for a substantially complete representation of insertion across the length of DNA. The DNA is then subjected to a functional selection. The effect of the selection is determined by amplifying DNA isolated from selected and control populations, and determining whether a particular region is over or underrepresented in the amplified DNA.

Genetic footprinting: insertional mutagenesis and genetic selection

Genetic mapping is provided by combinations of two related general procedures. In the first procedure, mapping is provided by identifying genetic regions from which DNA fragments derived from two individuals can combine to form extensive hybrids free of base mismatches. DNA is processed by a method that allows perfectly-matched hybrid DNA molecules formed between DNAs from the two individuals, to be separated from imperfectly-paired DNA hybrids or hybrids in which both strands are from the same individual's DNA. The perfectly-matched hybrid DNAs can then be labeled and the labeled DNA used as probes to identify loci of identity-by-descent between the two individuals. In the second procedure, nicks are introduced specifically into DNA hybrids formed between non-identical alleles from a region of heterozygosity in an individual diploid genome. The nicked DNA molecules are then specifically labeled to provide probes for identifying regions of heterozygosity in the genome of an individual.

Growing community of inventors

Stanford, CA, United States of America

Patrick O Brown