Kate Lawrenson
A5072088187- Ovarian cancer diagnosis and treatment
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- RNA Research and Splicing
- Prostate Cancer Treatment and Research
- Advanced Breast Cancer Therapies
- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- BRCA gene mutations in cancer
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- Cancer-related Molecular Pathways
- Cancer, Lipids, and Metabolism
- Endometriosis Research and Treatment
- Bioinformatics and Genomic Networks
- Endometrial and Cervical Cancer Treatments
- Genomics and Chromatin Dynamics
- Molecular Biology Techniques and Applications
- Cancer Cells and Metastasis
- Gene expression and cancer classification
- Renal and related cancers
- Ferroptosis and cancer prognosis
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Reproductive System and Pregnancy
- Chromatin Remodeling and Cancer
Cedars-Sinai Medical Center
2015-2024
Dana-Farber Cancer Institute
2023
University of California, Los Angeles
2022-2023
Eli and Edythe Broad Foundation
2023
Broad Institute
2023
University of Pennsylvania
2023
Cancer Research Center
2023
Los Angeles City College
2018
University of Southern California
2011-2016
Sinai Hospital
2016
Background Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which turn may promote formation reactive oxygen species, promoting DNA damage expression key regulatory cancer genes. As uncontrolled proliferation are hallmarks cancer, including epithelial ovarian (EOC), we hypothesized that inherited variation genes contributes EOC risk. Methods In total, samples were obtained from 14,525 case subjects...
Abstract Breast, ovarian, and prostate cancers are hormone-related may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these totaling 112,349 cases 116,421 controls of European ancestry, all together in pairs, identified at P < 10−8 seven new cross-cancer loci: three associated with susceptibility to (rs17041869/2q13/BCL2L11;...
Abstract Lineage plasticity, the ability of a cell to alter its identity, is an increasingly common mechanism adaptive resistance targeted therapy in cancer. An archetypal example development neuroendocrine prostate cancer (NEPC) after treatment adenocarcinoma (PRAD) with inhibitors androgen signaling. NEPC aggressive variant that aberrantly expresses genes characteristic (NE) tissues and no longer depends on androgens. Here, we investigate epigenomic basis this by profiling histone...
In Drosophila, normal and transformed cells compete with each other for survival in a process called cell competition. However, it is not known whether comparable phenomena also occur mammals. Scribble tumor suppressor protein Drosophila this study we examine the interface between Scribble-knockdown epithelial using Madin-Darby Canine Kidney (MDCK) expressing short hairpin RNA (shRNA) tetracycline-inducible manner. We observe that undergo apoptosis are apically extruded from epithelium when...
HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing serous leading us to hypothesize that variation this gene differentially associates with cancer risk according histological subtype. Here comprehensively map respect analyse DNA methylation expression profiles across subtypes. Different single-nucleotide polymorphisms associate invasive (rs7405776 odds ratio (OR)=1.13, P=3.1 × 10−10) (rs11651755 OR=0.77, P=1.6 10−8) cancer. Risk alleles for...
Although cancer-associated fibroblasts (CAFs) are viewed as a promising therapeutic target, the design of rational therapy has been hampered by two key obstacles. First, attempts to ablate CAFs have resulted in significant toxicity because currently used biomarkers cannot effectively distinguish activated from non-cancer associated and mesenchymal progenitor cells. Second, it is unclear whether different organs molecular functional properties that necessitate organ-specific designs. Our...
Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized the 3′ untranslated region at putative microRNA (miRNA)-binding sites represent functional targets influence EOC susceptibility. Here, we evaluate association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and risk 18,174 cases 26,134 controls from 43 studies genotyped through...
The homeobox A (HOXA) region of protein-coding genes impacts female reproductive system embryogenesis and ovarian carcinogenesis. 5-prime end HOXA includes three long non-coding RNAs (lncRNAs) (HOXA10-AS, HOXA11-AS, HOTTIP) that are underexplored in epithelial cancer (EOC). We evaluated whether common genetic variants these lncRNAs associated with EOC risk and/or have functional roles development. Using genome-wide association study data from 1,201 serous cases 2,009 controls, an exonic...
The human fallopian tube harbors the cell of origin for majority high-grade serous "ovarian" cancers (HGSCs), but its cellular composition, particularly epithelial component, is poorly characterized. We perform single-cell transcriptomic profiling around 53,000 individual cells from 12 primary specimens to map their major types. identify 10 subpopulations with diverse transcriptional programs. Based on signatures, we reconstruct a trajectory whereby secretory differentiate into ciliated via...
Abstract The functional consequences of somatic non-coding mutations in ovarian cancer (OC) are unknown. To identify regulatory elements (RE) and genes perturbed by acquired variants, here we establish epigenomic transcriptomic landscapes primary OCs using H3K27ac ChIP-seq RNA-seq, then integrate these with whole genome sequencing data from 232 OCs. We 25 frequently mutated elements, including an enhancer at 6p22.1 which associates differential expression ZSCAN16 (P = 6.6 × 10-4) ZSCAN12...
To identify molecular subclasses of clear cell ovarian carcinoma (CCOC) and assess their impact on clinical presentation outcomes.
PAX8 is a master transcription factor that essential during embryogenesis and promotes neoplastic growth. It expressed by the secretory cells lining female reproductive tract, its deletion development results in atresia of tract organs. Nearly all ovarian carcinomas express PAX8, knockdown apoptosis cancer cells. To explore role these tissues, we purified protein complex from nonmalignant fallopian tube high-grade serous carcinoma cell lines. We found was member large chromatin remodeling...
While the mutational and transcriptional landscapes of renal cell carcinoma (RCC) are well-known, epigenome is poorly understood. We characterize clear (ccRCC), papillary (pRCC), chromophobe RCC (chRCC) by using ChIP-seq, ATAC-Seq, RNA-seq, SNP arrays. integrate 153 individual data sets from 42 patients nominate 50 histology-specific master transcription factors (MTF) to define histologic subtypes, including EPAS1 ETS-1 in ccRCC, HNF1B pRCC, FOXI1 chRCC. confirm MTFs via immunohistochemistry...
Most epithelial ovarian cancers are diagnosed postmenopausally, although the well-established epidemiological risk factors (parity, oral contraceptive use) premenopausal. We hypothesized that accumulation of senescent fibroblasts, together with concomitant loss presenescent fibroblasts within cortex, promotes initiation and early development cancer from surface (OSE) cells. To test this, we established immortalized OSE (IOSE) cell lines mimic neoplastic transformation by overexpressing CMYC...