Inventors list

Assignees list

Classification tree browser

Top 100 Inventors

Top 100 Assignees


Kenneth W. Kinzler, Bel Air US

Kenneth W. Kinzler, Bel Air, MD US

Patent application numberDescriptionPublished
20080318321Methods for Generating Hypermutable Microbes - Bacteria are manipulated to create desirable output traits using dominant negative alleles of mismatch repair proteins. Enhanced hypermutation is achieved by combination of mismatch repair deficiency and exogenously applied mutagens. Stable bacteria containing desirable output traits are obtained by restoring mismatch repair activity to the bacteria.12-25-2008
20090017030Endothelial Cell Expression Patterns - To gain a better understanding of tumor angiogenesis, new techniques for isolating endothelial cells (ECs) and evaluating gene expression patterns were developed. When transcripts from ECs derived from normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed 79 differentially expressed genes, including 46 that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions of the liver. These results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level, and have significant implications for the development of anti-angiogenic therapies in the future.01-15-2009
20090117546Disease detection by digital protein truncation assays - Genetic diseases can be diagnosed by detection of mutations in causative genes. Protein truncation assays can be used to detect gene products of truncation-type mutations. However, the sensitivity of the assays is often insufficient to detect mutations present in a sample of DNA at a low frequency. Sensitivity can be increased by dividing samples so that the signal generated by a mutant allele comprises a larger fraction of the total alleles than prior to dividing. Thus a previously undetectable signal generated by the mutant allele can become detectable in the assay. Such increased sensitivity permits detection at early stages and in samples having high levels of other alleles.05-07-2009
20090123928Genomic Landscapes of Human Breast and Colorectal Cancers - Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalogue the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene “mountains” and a much larger number of gene “hills” that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.05-14-2009
20090137427Method for generating hypermutable organisms - Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. The enhanced rate of mutation can be further augmented using mutagens. Moreover, the hypermutability of mismatch repair deficient cells can be remedied to stabilize cells or mammals with useful mutations.05-28-2009
20090233270Secreted and cytoplasmic tumor endothelial markers - To gain a better understanding of tumor angiogenesis, new techniques for isolating endothelial cells (ECs) and evaluating gene expression patterns were developed. When transcripts from ECs derived from normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed many differentially expressed genes, including a large nujber of genes that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions fo the liver. Theses results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level, and have significant implications for the development of anti-angiogenic. 09-17-2009
20100137413MICRORNAOME - MicroRNAs (miRNAs) are a class of small noncoding RNAs that have important regulatory roles in multicellular organisms. The public miRNA database contains 321 human miRNA sequences, 234 of which have been experimentally verified. To explore the possibility that additional miRNAs are present in the human genome, we have developed an experimental approach called miRNA serial analysis of gene expression (miRAGE) and used it to perform the largest experimental analysis of human miRNAs to date. Sequence analysis of 273,966 small RNA tags from human colorectal cells allowed us to identify 200 known mature miRNAs, 133 novel miRNA candidates, and 112 previously uncharacterized miRNA* forms. To aid in the evaluation of candidate miRNAs, we disrupted the Dicer locus in three human colorectal cancer cell lines and examined known and novel miRNAs in these cells. The miRNAs are useful to diagnose and treat cancers.06-03-2010
20100184100Tyrosine Kinome - Protein kinases are important signaling molecules involved in tumorigenesis. Mutational analysis of the human tyrosine kinase gene family (98 genes) identified somatic alterations in −20% of colorectal cancers, with the majority of mutations occurring in NTRK3, FES, GUCY2F and a previously uncharacterized tyrosine kinase gene called MCCK/MLK4. Most alterations were in conserved residues affecting key regions of the kinase domain. These data represent a paradigm for the unbiased analysis of signal transducing genes in cancer and provide useful targets for therapeutic intervention.07-22-2010
20100190153SINGLE-MOLECULE PCR ON MICROPARTICLES IN WATER-IN-OIL EMULSIONS - Modulation of the viscosity of the oil phase of a microemulsion used for amplification of DNA on a bead increases the homogeneity of product beads and the amount of amplified DNA per bead. Moreover the number of separate microemulsion populations that can be formed in parallel is increased using multi-well plates and mixer mill disruptor machines designed to lyse biological samples.07-29-2010
20110033466HUMAN TRANSCRIPTOMES - Global gene expression patterns have been characterized in normal and cancerous human cells using serial analysis of gene expression (SAGE). Cancer cell-specific, cell-type specific, and ubiquitously expressed genes have been identified. This information can be used to provide combinations of cell type- and cancer-specific gene probes, as well as methods of using these probes to identify particular cell types, screen for useful drugs, reduce cancer-specific gene expression, standardize gene expression, and restore function to a diseased cell or tissue.02-10-2011
20110059434P13k pathway mutations in cancer - Given the important role of protein kinases in pathways affecting cellular growth and invasion, we have analyzed 340 serine/threonine kinases for genetic mutations in colorectal cancers. Mutations in eight genes were identified, including three members of the phosphatidylinositol-3-kinase (PI3K) pathway; the alterations in the latter genes each occurred in different tumors and did not overlap with mutations in PIK3CA or other non-serine-threonine kinase (STK) members of the PI3K pathway, suggesting that mutations in any of these genes had equivalent tumorigenic effects. These data demonstrate that the PI3K pathway is a major target for mutational activation in colorectal cancers and provide new opportunities for therapeutic intervention.03-10-2011
20110059435 Methods for Beaming - Improvements on the basic method used for BEAMing increase sensitivity and increase the signal-to-noise ratio. The improvements have permitted the determination of intrinsic error rates of various DNA polymerases and have permitted the detection of rare and subtle mutations in DNA isolated from plasma of cancer patients.03-10-2011
20110104059Membrane Associated Tumor Endothelium Markers - To gain a better understanding of tumor angiogenesis endothelial cells (ECs) were isolated and gene expression patterns were evaluated. When transcripts from ECs derived from normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed differentially expressed genes, including many that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions of the liver. These results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level.05-05-2011

Patent applications by Kenneth W. Kinzler, Bel Air, MD US