Patents by Inventor Mihaela Campan
Mihaela Campan has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 9797005Abstract: Particular aspects provide novel, high-throughput methods to quantify DNA methylation (e.g., at a single-base resolution) in an allele-specific manner. The methods comprise use of an allele-specific sequence polymorphism (e.g., allele-specific single nucleotide polymorphism; SNP) in sufficient proximity to a CpG methylation site to provide for distinguishing the methylation levels between two alleles. In particular aspects, after bisulfite modification, the genomic DNA region is PCR-amplified, and the product subjected to allele-specific pyrosequencing, and the percentage of methylation determined based on the percentage of cytosine to thymidine conversion. In further embodiments, MethyLight™ is used after bisulfite treatment. The inventive methodology has, for example, substantial utility for affording quantitative analyses in the regulation of analyses of X-inactivation, the allele-specific expression of genes (e.g., in the immune system) and junk DNA, etc.Type: GrantFiled: November 22, 2006Date of Patent: October 24, 2017Assignee: University of Southern CaliforniaInventors: Mihaela Campan, Peter W. Laird, Allen S. Yang, Hui-Lee Wong
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Publication number: 20160289768Abstract: Particular aspects confirm the existence of a CpG island methylator phenotype (CIMP) in colorectal cancer, and provide novel validated DNA methylation markers associated with CIMP. Additional aspects provide novel methods and compositions for: determining CIMP status in colorectal cancers, determining the relationship between CIMP status and other molecular features of the cancers (e.g., BRAF mutation, KRAS mutation, and MSI status); determining the relationship between CIMP status and other variables (e.g., age, sex, tumor location, family history, race, country of origin, tumor characteristics (including, tumor type, tumor grade, invasive margin characteristics, lymphocyte infiltration characteristics, direct spread, lymph node spread, venous spread, and type of residual adjacent polyp, if present)); and determining, between subgroups defined by CIMP status and BRAF mutations, effects of selected risk factors (e.g.Type: ApplicationFiled: March 9, 2016Publication date: October 6, 2016Inventors: Peter W. Laird, Kimberly D. Siegmund, Mihaela Campan, Daniel J. Weisenberger, Tiffany I. Long
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Publication number: 20160130643Abstract: A method of copying a methylated nucleic acid molecule is provided. The method includes copying a nucleic acid molecule into a plurality of nucleic acid molecules; and contacting the plurality of nucleic acid molecules with a DNA methyltransferase enzyme and an E3 ubiquitin ligase. The method results in the copying of the methylated nucleic acid molecule.Type: ApplicationFiled: October 30, 2015Publication date: May 12, 2016Applicant: University of Southern CaliforniaInventors: Ite A. Laird-Offringa, Jinkeng Asong, Mihaela Campan, Po-Han Chen, Crystal N. Marconett, Ian Stuart Haworth
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Patent number: 9290803Abstract: Provided are novel sensitive methylation assays referred to herein as Digital MethyLight, comprising stochastically distributing and compartmentalizing bisulfite-treated genomic DNA over multiple PCR reaction wells for detection of individually methylated DNA molecules in a large background of unmethylated DNA. Digital Bisulfite Genomic DNA Sequencing methods are also provided for high-resolution DNA methylation information without subcloning. Background signal and PCR contaminants are diluted, while the ratio of primer to methylated template DNA is kept high. Preferably, biological fluid (e.g., urine, blood-based (e.g., plasma and/or serum)) samples are analyzed for cancer diagnosis, prognosis and surveillance. Multiplexed PCR formats may be implemented to enhance when using small DNA amounts.Type: GrantFiled: April 14, 2008Date of Patent: March 22, 2016Assignee: University of Southern CaliforniaInventors: Peter W. Laird, Binh N. Trinh, Mihaela Campan, Daniel J. Weisenberger
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Patent number: 8642263Abstract: Preferred aspects provide novel high-throughput, sensitive methods (e.g., real-time PCR-based (MethyLight™) reactions) for detection and/or measurement of global genomic 5-methylcytosine content, based on measurement of DNA methylation of Alu, LINE-1 repetitive sequences, and the chromosome 1 centromeric satellite alpha and juxtacentromeric satellite 2 repeat sequences. Additional aspects provide sensitive methods for determining the amount of a DNA (e.g., in formalin-fixed, paraffin-embedded tissues). Combined (mean) use of Alu and Sat2 repeat methylation measurements provides for a surprisingly close correlation with global genomic 5-methylcytosine content measurements obtained by HPLC. Methylation of Alu repeats was determined to be closely associated with HPLC-based global methylation levels, as was methylation of satellite 2 and LINE-1 global genomic 5-methylcytosine content.Type: GrantFiled: November 10, 2005Date of Patent: February 4, 2014Assignee: University of Southern CaliforniaInventors: Peter W. Laird, Daniel J. Weisenberger, Mihaela Campan, Tifany I. Long
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Publication number: 20120219946Abstract: Particular aspects confirm the existence of a CpG island methylator phenotype (CIMP) in colorectal cancer, and provide novel validated DNA methylation markers associated with CIMP. Additional aspects provide novel methods and compositions for: determining CIMP status in colorectal cancers, determining the relationship between CIMP status and other molecular features of the cancers (e.g., BRAF mutation, KRAS mutation and MSI status); determining the relationship between CIMP status and other variables (e.g., age, sex, tumor location, family history, race, country of origin, tumor characteristics (including, tumor type, tumor grade, invasive margin characteristics, lymphocyte infiltration characteristics, direct spread, lymph node spread, venous spread and type of residual adjacent polyp, if present)); and determining, between subgroups defined by CIMP status and BRAF mutations, effects of selected risk factors (e.g.Type: ApplicationFiled: February 3, 2012Publication date: August 30, 2012Applicant: University of Southern CaliforniaInventors: Peter W. Laird, Kimberly D. Siegmund, Mihaela Campan, Daniel J. Weisenberger, Tiffany I. Long
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Patent number: 8110361Abstract: Particular aspects confirm the existence of a CpG island methylator phenotype (CIMP) in colorectal cancer, and provide novel validated DNA methylation markers associated with CIMP. Additional aspects provide novel methods and compositions for: determining CIMP status in colorectal cancers, determining the relationship between CIMP status and other molecular features of the cancers (e.g., BRAF mutation, KRAS mutation and MSI status); determining the relationship between CIMP status and other variables (e.g., age, sex, tumor location, family history, race, country of origin, tumor characteristics (including, tumor type, tumor grade, invasive margin characteristics, lymphocyte infiltration characteristics, direct spread, lymph node spread, venous spread and type of residual adjacent polyp, if present)); and determining, between subgroups defined by CIMP status and BRAF mutations, effects of selected risk factors (e.g.Type: GrantFiled: May 2, 2006Date of Patent: February 7, 2012Assignee: University of Southern California USC Stevens Center for InnovationInventors: Peter W. Laird, Kimberly D. Siegmund, Mihaela Campan, Daniel J. Weisenberger, Tiffany I. Long
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Publication number: 20090123915Abstract: Preferred aspects provide novel high-throughput, sensitive methods (e.g., real-time PCR-based (MethyLight™) reactions) for detection and/or measurement of global genomic 5-methylcytosine content, based on measurement of DNA methylation of Alu, LINE-1 repetitive sequences, and the chromosome 1 centromeric satellite alpha and juxtacentromeric satellite 2 repeat sequences. Additional aspects provide sensitive methods for determining the amount of a DNA (e.g., in formalin-fixed, paraffin-embedded tissues). Combined (mean) use of Alu and Sat2 repeat methylation measurements provides for a surprisingly close correlation with global genomic 5-methylcytosine content measurements obtained by HPLC. Methylation of Alu repeats was determined to be closely associated with HPLC-based global methylation levels, as was methylation of satellite 2 and LINE-1 global genomic 5-methylcytosine content.Type: ApplicationFiled: November 10, 2005Publication date: May 14, 2009Applicant: UNIVERSITY OF SOUTHERN CALIFORNIAInventors: Peter W. Laird, Daniel J. Weisenberger, Mihaela Campan, Tiffany I. Long
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Publication number: 20090053706Abstract: Particular aspects confirm the existence of a CpG island methylator phenotype (CIMP) in colorectal cancer, and provide novel validated DNA methylation markers associated with CIMP. Additional aspects provide novel methods and compositions for: determining CIMP status in colorectal cancers, determining the relationship between CIMP status and other molecular features of the cancers (e.g., BRAF mutation, KRAS mutation and MSI status); determining the relationship between CIMP status and other variables (e.g., age, sex, tumor location, family history, race, country of origin, tumor characteristics (including, tumor type, tumor grade, invasive margin characteristics, lymphocyte infiltration characteristics, direct spread, lymph node spread, venous spread and type of residual adjacent polyp, if present)); and determining, between subgroups defined by CIMP status and BRAF mutations, effects of selected risk factors (e.g.Type: ApplicationFiled: May 2, 2006Publication date: February 26, 2009Applicant: University of Southern CaliforniaInventors: Peter W. Laird, KImberly D. Siegmund, Mihaela Campan, Daniel J. Weisenberg, Tiffany I. Long
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Publication number: 20080286787Abstract: Particular aspects provide novel, high-throughput methods to quantify DNA methylation (e.g., at a single-base resolution) in an allele-specific manner. The methods comprise use of an allele-specific sequence polymorphism (e.g., allele-specific single nucleotide polymorphism; SNP) in sufficient proximity to a CpG methylation site to provide for distinguishing the methylation levels between two alleles. In particular aspects, after bisulfite modification, the genomic DNA region is PCR-amplified, and the product subjected to allele-specific pyrosequencing, and the percentage of methylation determined based on the percentage of cytosine to thymidine conversion. In further embodiments, MethyLight™ is used after bisulfite treatment. The inventive methodology has, for example, substantial utility for affording quantitative analyses in the regulation of analyses of X-inactivation, the allele-specific expression of genes (e.g., in the immune system) and junk DNA, etc.Type: ApplicationFiled: November 22, 2006Publication date: November 20, 2008Applicant: University of Southern CaliforniaInventors: Mihaela Campan, Peter W. Laird, Allen S. Yang, Hui-Lee Wong
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Publication number: 20080254474Abstract: Provided are novel sensitive methylation assays referred to herein as Digital MethyLight, comprising stochastically distributing and compartmentalizing bisulfite-treated genomic DNA over multiple PCR reaction wells for detection of individually methylated DNA molecules in a large background of unmethylated DNA. Digital Bisulfite Genomic DNA Sequencing methods are also provided for high-resolution DNA methylation information without subcloning. Background signal and PCR contaminants are diluted, while the ratio of primer to methylated template DNA is kept high. Preferably, biological fluid (e.g., urine, blood-based (e.g., plasma and/or serum)) samples are analyzed for cancer diagnosis, prognosis and surveillance. Multiplexed PCR formats may be implemented to enhance when using small DNA amounts.Type: ApplicationFiled: April 14, 2008Publication date: October 16, 2008Applicant: University of Southern CaliforniaInventors: Peter W. Laird, Binh N. Trinh, Mihaela Campan, Daniel J. Weisenberger