Ji-Heui Seo
A5019838007- Prostate Cancer Treatment and Research
- Epigenetics and DNA Methylation
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Lung Cancer Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- Cancer-related molecular mechanisms research
- Ovarian cancer diagnosis and treatment
- Genetic Associations and Epidemiology
- RNA modifications and cancer
- Cancer, Lipids, and Metabolism
- Prostate Cancer Diagnosis and Treatment
- Mechanisms of cancer metastasis
- RNA Research and Splicing
- Renal cell carcinoma treatment
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Circadian rhythm and melatonin
- Genetics, Aging, and Longevity in Model Organisms
- Bioinformatics and Genomic Networks
- Cancer-related gene regulation
- Ferroptosis and cancer prognosis
- FOXO transcription factor regulation
- Metastasis and carcinoma case studies
- PARP inhibition in cancer therapy
Center for Neuro-Oncology
2023-2025
Dana-Farber Cancer Institute
2016-2025
Harvard University
2018-2024
University of California, Los Angeles
2022
Broad Institute
2021-2022
Dana-Farber Brigham Cancer Center
2020-2021
Brigham and Women's Hospital
2020-2021
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...
Abstract Neuroendocrine carcinomas (NEC) are tumors expressing markers of neuronal differentiation that can arise at different anatomic sites but have strong histological and clinical similarities. Here we report the chromatin landscapes a range human NECs show convergence to activation common epigenetic program. With particular focus on treatment emergent neuroendocrine prostate cancer (NEPC), analyze cell lines, patient-derived xenograft (PDX) models samples existence two distinct NEPC...
Abstract c-MYC (MYC) is a major driver of prostate cancer tumorigenesis and progression. Although MYC overexpressed in both early metastatic disease associated with poor survival, its impact on transcriptional reprogramming remains elusive. We demonstrate that overexpression significantly diminishes the androgen receptor (AR) program (the set genes directly targeted by AR protein) luminal cells without altering expression. Analyses clinical specimens reveal concurrent low high programs...
Abstract Although circulating tumor DNA (ctDNA) assays are increasingly used to inform clinical decisions in cancer care, they have limited ability identify the transcriptional programs that govern phenotypes and their dynamic changes during course of disease. To address these limitations, we developed a method for comprehensive epigenomic profiling from 1 ml patient plasma. Using an immunoprecipitation-based approach targeting histone modifications methylation, measured 1,268 profiles...
Abstract While the effect of amplification-induced oncogene expression in cancer is known, impact copy-number gains on “bystander” genes less understood. We create a comprehensive map dosage compensation by integrating and copy number profiles from over 8000 tumors The Cancer Genome Atlas cell lines Cell Line Encyclopedia. Additionally, we analyze 17 open reading frame screens to identify toxic cells when overexpressed. Combining these approaches, propose class ‘Amplification-Related Gain Of...
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...
Androgen receptor (AR) in prostate cancer (PCa) can drive transcriptional repression of multiple genes including MYC, and supraphysiological androgen is effective some patients. Here, we show that this independent AR chromatin binding driven by coactivator redistribution, through conformation capture methods disruption the interaction between MYC super-enhancer within PCAT1 gene promoter. Conversely, deprivation vitro vivo increases expression. In parallel, global activity suppressed...
The CaCTS algorithm nominates cancer cell master transcription factors and guides a model of ovarian regulatory circuitry.
In prostate cancer, androgen receptor (AR)-targeting agents are very effective in various disease stages. However, therapy resistance inevitably occurs, and little is known about how tumor cells adapt to bypass AR suppression. Here, we performed integrative multiomics analyses on tissues isolated before after 3 months of AR-targeting enzalutamide monotherapy from patients with high-risk cancer enrolled a neoadjuvant clinical trial. Transcriptomic demonstrated that inhibition drove tumors...
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...
Abstract Newly diagnosed prostate cancers differ dramatically in mutational composition and lethality. The most accurate clinical predictor of lethality is tumor tissue architecture, quantified as grade. To interrogate the evolutionary origins cancer heterogeneity, we analyzed 666 whole genomes. We identified a compendium 223 recurrently mutated driver regions, influencing downstream processes gene expression. validated individual germline variants that predispose tumors to acquire specific...
Long noncoding RNAs (lncRNAs) have emerged as critical regulators of tumorigenesis, and yet their mechanistic roles remain challenging to characterize. Here, we integrate functional proteomics with lncRNA-interactome profiling characterize Urothelial Cancer Associated 1 (UCA1), a candidate driver ovarian cancer development. Reverse phase protein array (RPPA) analysis indicates that UCA1 activates transcription coactivator YAP its target genes. In vivo RNA antisense purification (iRAP)...
Neuroendocrine prostate cancer (NEPC) is a resistance phenotype that emerges in men with metastatic castration-resistant adenocarcinoma (CR-PRAD) and has important clinical implications, but challenging to detect practice. Herein, we report novel tissue-informed epigenetic approach noninvasively NEPC.
Androgen receptor (AR) signaling is the central driver of prostate cancer across disease states. While androgen deprivation therapy (ADT) effective in initial treatment cancer, resistance to ADT or next-generation pathway inhibitors invariably arises, most commonly through re-activation AR axis. Thus, orthogonal approaches inhibit advanced are essential. Here, via genome-scale CRISPR-Cas9 screening, we identify protein arginine methyltransferase 1 (PRMT1) as a critical mediator expression...
African-American (AA) men are more likely to be diagnosed with and die from prostate cancer than European American (EA) men. Despite the central role of androgen receptor (AR) transcription factor in cancer, little is known about contribution epigenetics observed racial disparities. We performed AR chromatin immunoprecipitation sequencing on primary tumors AA EA men, finding that sites greater binding intensity relative enriched for lipid metabolism immune response genes. Integration...
539 Background: Clear cell renal carcinoma (ccRCC) with sarcomatoid differentiation (sRCC) is associated poor survival. Recent studies have shown downregulation of hypoxia-related pathways in sRCC (Motzer et al., Cancer Cell, 2020; El Zarif, Semaan Cell Reports, 2024). In this study, we sought to compare HIF2α expression levels ccRCC, and without investigate clinical outcomes patients (pts) treated inhibitors (HIF2αi). Methods: To assess gene sRCC, RNA-seq data was collected from 2 trials:...
Metastatic castration-resistant prostate cancers (mCRPCs) are treated with therapies that antagonize the androgen receptor (AR). Nearly all patients develop resistance to AR-targeted (ARTs). Our previous work identified CREB5 as an upregulated target gene in human mCRPC promoted clinically approved ART. The mechanisms by which promotes progression of or other remains elusive. Integrating ChIP-seq and rapid immunoprecipitation mass spectroscopy endogenous proteins, we report cells...
Abstract Androgen receptor (AR) drives prostate cancer (PCa) development and progression. AR chromatin binding profiles are highly plastic form recurrent programmatic changes that differentiate disease stages, subtypes patient outcomes. While prior studies focused on concordance between subgroups, inter-tumor heterogeneity of enhancer selectivity remains unexplored. Here we report high levels in human primary tumors, overlap with observed healthy epithelium. Such has functional consequences,...