A5036500285- Cancer Immunotherapy and Biomarkers
- Prostate Cancer Treatment and Research
- Cancer Diagnosis and Treatment
- Systemic Sclerosis and Related Diseases
- Renal cell carcinoma treatment
- PARP inhibition in cancer therapy
- Cancer, Lipids, and Metabolism
- Bladder and Urothelial Cancer Treatments
- Science, Research, and Medicine
- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Health Systems, Economic Evaluations, Quality of Life
- Metal-Catalyzed Oxygenation Mechanisms
- RNA modifications and cancer
- Metabolism, Diabetes, and Cancer
- Advanced Breast Cancer Therapies
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Hormonal and reproductive studies
- Genetic factors in colorectal cancer
- Prostate Cancer Diagnosis and Treatment
- Glutathione Transferases and Polymorphisms
- CRISPR and Genetic Engineering
- Estrogen and related hormone effects
- Inflammatory Bowel Disease
Dana-Farber Cancer Institute
2016-2025
Harvard University
2011-2024
Kidney Centre
2023
Cleveland Clinic
2023
City Of Hope National Medical Center
2023
Memorial Sloan Kettering Cancer Center
2023
Icahn School of Medicine at Mount Sinai
2011
New York University
1999-2003
Columbia University Irving Medical Center
1999
Significance We report that enhancer RNAs (eRNAs), a class of long noncoding RNAs, participate in the androgen receptor (AR)-dependent looping complex enhances spatial communication distal enhancers and target promoters, leading to transcriptional activation events. Furthermore, our data show KLK3 eRNA (KLK3e) selectively gene expression AR-regulated genes, provide evidence for positive regulatory loop which AR-dependent transcription is modulated by an intermediate eRNA. These findings may...
Abstract BACKGROUND Recent studies show that microRNAs (miRNAs), small non‐coding RNAs negatively regulate gene expression, may have potential for monitoring cancer status. We investigated circulating miRNAs in prostate be associated with the progression of hormone‐sensitive primary tumors to metastatic castration resistant (CRPC) after androgen deprivation therapy. METHODS Using genome‐wide expression profiling by TaqMan Human MicroRNA Arrays (Applied Biosystems) and/or quantitative...
Translocation renal cell carcinoma (tRCC) is a poorly characterized subtype of kidney cancer driven by MiT/TFE gene fusions. Here, we define the landmarks tRCC through an integrative analysis 152 patients with identified across genomic, clinical trial, and retrospective cohorts. Most tRCCs harbor few somatic alterations apart from fusions homozygous deletions at chromosome 9p21.3 (19.2% cases). Transcriptionally, display heightened NRF2-driven antioxidant response that associated resistance...
Androgen-dependent prostate cancer typically progresses to castration-resistant (CRPC) after the androgen deprivation therapy. MicroRNAs (miR) are noncoding small RNAs (19-25nt) that play an important role in regulation of gene expression. Recent studies have shown miR expression patterns significantly different normal and neoplastic epithelial cells. However, importance miRs development CRPC has not yet been explored. By performing genome-wide profiling miRs, we found levels several...
Significance The results of the recent clinical trials, ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) and Systemic Advanced or Metastatic Cancer: Evaluation Drug Efficacy (STAMPEDE), suggest a significant contribution androgen receptor signaling to sensitivity docetaxel prostate cancer. This study provides evidence that KDM5D (lysine-specific demethylase 5D) encoded on Y chromosome plays an important role by interacting...
Statin use has been associated with improved prostate cancer outcomes. Dehydroepiandrosterone sulfate (DHEAS) is a precursor of testosterone and substrate for SLCO2B1, an organic anionic transporter. We previously demonstrated that genetic variants SLCO2B1 correlated time to progression (TTP) during receipt androgen deprivation therapy (ADT). Statins also enter cells, thus we hypothesized they may compete DHEAS uptake by the tumor cells.To evaluate whether statin prolongs TTP ADT...
Defects in genes the DNA repair pathways significantly contribute to prostate cancer progression. We hypothesize that overexpression of may also drive poorer outcomes cancer. The ribonucleotide reductase small subunit M2 (RRM2) is essential for synthesis and by producing dNTPs. It frequently overexpressed cancers, but very little known about its function
Abstract Purpose: We evaluated the association of PSA and androgen receptor splice variant-7 (AR-V7) transcript levels in patients' blood with time to treatment failure (TTF) overall survival (OS) abiraterone acetate and/or enzalutamide castration-resistant prostate cancer (CRPC) patients. Experimental Design: RNA AR-V7 peripheral collected before were quantified using droplet digital-PCR retrospective cohorts treated (N = 81) or 51) for CRPC. Multivariable Cox regression adjusted known...
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 BACKGROUND We have previously identified seven miRs‐ miR‐221 , ‐222 ‐23b ‐27b ‐15a ‐16‐1 and ‐203 that are differentially expressed in the hormone sensitive LNCaP cell line resistant LNCaP‐abl hypothesized these miRs may characterize certain subtypes of human castration prostate cancer (CRPC). METHODS Functional studies culture systems been performed to determine effect alternated expression level on cellular response androgen treatment. To clinical relevance patterns miRs, we...
Epigenetic modifications control cancer development and clonal evolution in various types. Here, we show that loss of the male-specific histone demethylase lysine-specific 5D (KDM5D) encoded on Y chromosome epigenetically modifies methylation marks alters gene expression, resulting aggressive prostate cancer. Fluorescent situ hybridization demonstrated segmental or total deletion cells is one causes decreased KDM5D mRNA expression. The result ChIP-sequencing analysis revealed preferably...
Abstract Purpose: Oncogenic alterations of the PI3K/AKT pathway occur in >40% patients with metastatic castration-resistant prostate cancer, predominantly via PTEN loss. The significance other PI3K components cancer is largely unknown. Experimental Design: Patients this study underwent tumor sequencing using MSK-IMPACT clinical assay to capture single-nucleotide variants, insertions, and deletions; copy-number alterations; structural rearrangements, or were profiled through Cancer...
Abstract BACKGROUND Enhanced androgen receptor (AR) activity by increased testosterone availability may play important roles in prostate cancer progressing to castration resistant state. Comparison of expression profiles dependent and independent tumors demonstrated a marked increase the UDP‐glucuronosyltransferase 2B15 (UGT2B15), an catabolic enzyme. We investigated mechanisms controlling differential UGT2B15 B17 response treatments. METHODS Gene was determined RT‐PCR. The association AR...
Renal cell carcinoma (RCC) of variant histology comprises approximately 20% kidney cancer diagnoses, yet the optimal therapy for these patients and factors that impact immunotherapy response remain largely unknown. To better understand determinants in this population, we characterized blood- tissue-based immune markers with RCC, or any RCC sarcomatoid differentiation, enrolled a phase II clinical trial atezolizumab bevacizumab. Baseline circulating (plasma) inflammatory cytokines were highly...
Abstract Mechanisms by which non-coding RNAs contribute to the progression of hormone-sensitive prostate cancer (PCa) (HSPC) castration-resistant PCa (CRPC) remain largely unknown. We previously showed that microRNA-221/222 is up-regulated in CRPC and plays a critical role modulating androgen receptor function during development. With further investigation, we characterized putative promoter region located 23.3 kb upstream miR-221/222 gene, this differentially activated LNCaP-Abl cells,...
Abstract Genome-wide association studies have detected more than 30 inherited prostate cancer risk variants. While clearly associated with risk, their relationship clinical outcome, particularly cancer–specific mortality, is less well known. We investigated whether the variants are various measures of disease aggressiveness and mortality. In a cohort 3,945 men European ancestry cancer, we genotyped 36 single nucleotide polymorphisms (SNP): 35 known one SNP (rs4054823) that was recently...
To validate the association of three previously demonstrated SLCO2B1 germline variants with time to progression (TTP) in patients receiving androgen-deprivation therapy (ADT), and evaluate if genetic impacted overall survival (OS) for prostate cancer (PC).
Although there are molecularly distinct subtypes of prostate cancer, no molecular classification system is used clinically. The ribonucleotide reductase small subunit M2 (RRM2) gene plays an oncogenic role in many cancers. Our previous study elucidated comprehensive mechanisms RRM2 cancer (PC). Given the potent functions RRM2, we set out to determine whether signature can be identify aggressive PC. We applied ontology and pathway analysis RNA-seq datasets from PC cells overexpressing RRM2....
Abiraterone acetate (AA), an inhibitor of cytochrome P450 17alpha-hydroxylase/17, 20 lyase, is FDA-approved drug for advanced prostate cancer. However, not all patients respond to AA, and AA resistance ultimately develops in who initially respond. We aimed identify mechanisms cancer cells.We established several AA-resistant cell lines performed a comprehensive study on involved development. RNA sequencing phospho-kinase array screenings were discover that the cAMP-response element CRE...