A5028420362- Prostate Cancer Treatment and Research
- Cancer Immunotherapy and Biomarkers
- Radiopharmaceutical Chemistry and Applications
- Cancer Genomics and Diagnostics
- Neuroendocrine Tumor Research Advances
- Bladder and Urothelial Cancer Treatments
- Glioma Diagnosis and Treatment
- Lung Cancer Research Studies
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- PARP inhibition in cancer therapy
- Cancer-related molecular mechanisms research
- Brain Metastases and Treatment
- Hippo pathway signaling and YAP/TAZ
- Phagocytosis and Immune Regulation
- Microtubule and mitosis dynamics
- Radiomics and Machine Learning in Medical Imaging
- Mechanisms of cancer metastasis
- Chromatin Remodeling and Cancer
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Neuroblastoma Research and Treatments
- Brain Tumor Detection and Classification
- Medical Imaging Techniques and Applications
- Genetic factors in colorectal cancer
Cornell University
2016-2025
New York Hospital Queens
2018-2025
NewYork–Presbyterian Hospital
2018-2025
Lander Institute
2017-2025
Case Western Reserve University
2021-2024
Weill Cornell Medicine
2016-2024
Cincinnati Children's Hospital Medical Center
2024
Nationwide Children's Hospital
2024
University of Southern California
2024
Presbyterian Hospital
2018-2024
Abstract A major hurdle in the study of rare tumors is a lack existing preclinical models. Neuroendocrine prostate cancer an uncommon and aggressive histologic variant that may arise de novo or as mechanism treatment resistance patients with pre-existing castration-resistant cancer. There are few available models to neuroendocrine Here, we report generation characterization tumor organoids derived from needle biopsies metastatic lesions four patients. We demonstrate genomic, transcriptomic,...
Abstract Purpose: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of that may develop de novo or as a mechanism treatment resistance. N-myc capable driving NEPC progression. Alisertib inhibits the interaction between and its stabilizing factor Aurora-A, inhibiting signaling, suppressing tumor growth. Patients Methods: Sixty men were treated with alisertib 50 mg twice daily for 7 days every 21 days. Eligibility included metastatic at least one: small-cell neuroendocrine...
Abstract Cytosolic DNA is characteristic of chromosomally unstable metastatic cancer cells, resulting in constitutive activation the cGAS–STING innate immune pathway. How tumors co-opt inflammatory signaling while evading surveillance remains unknown. Here, we show that ectonucleotidase ENPP1 promotes metastasis by selectively degrading extracellular cGAMP, an immune-stimulatory metabolite whose breakdown products include suppressor adenosine. loss suppresses metastasis, restores tumor...
Upper tract urothelial carcinoma (UTUC) is characterized by a distinctly aggressive clinical phenotype. To define the biological features driving this phenotype, we performed an integrated analysis of whole-exome and RNA sequencing UTUC. Here report several key insights from our molecular dissection disease: 1) Most UTUCs are luminal-papillary; 2) UTUC has T-cell depleted immune contexture; 3) High FGFR3 expression enriched in correlates with its microenvironment; 4) Sporadic lower total...
Despite recent therapeutic advances, prostate cancer remains a leading cause of cancer-related death. A subset castration-resistant cancers become androgen receptor (AR) signaling independent and develop neuroendocrine (NEPC) features through lineage plasticity. These NEPC tumors, associated with aggressive disease poor prognosis, are driven, in part, by aberrant expression N-Myc, mechanisms that remain unclear. Integrative analysis the N-Myc transcriptome, cistrome, interactome using vivo,...
In castration-resistant prostate cancer (CRPC), the loss of androgen receptor (AR) dependence leads to clinically aggressive tumors with few therapeutic options. We used ATAC-seq (assay for transposase-accessible chromatin sequencing), RNA-seq, and DNA sequencing investigate 22 organoids, six patient-derived xenografts, 12 cell lines. identified well-characterized AR-dependent neuroendocrine subtypes, as well two AR-negative/low groups: a Wnt-dependent subtype, stem cell-like (SCL) subtype...
Advanced prostate cancer initially responds to hormonal treatment, but ultimately becomes resistant and requires more potent therapies. One mechanism of resistance observed in around 10-20% these patients is lineage plasticity, which manifests a partial or complete small cell neuroendocrine (NEPC) phenotype. Here, we investigate the role mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex NEPC. Using large patient datasets, patient-derived organoids lines, identify mSWI/SNF subunits...
The activity and survival of retinal photoreceptors depend on support functions performed by the pigment epithelium (RPE) oxygen nutrients delivered blood vessels in underlying choroid. By combining single-cell bulk RNA sequencing, we categorized mouse RPE/choroid cell types characterized tissue-specific transcriptomic features choroidal endothelial cells. We found that endothelium adjacent to RPE expresses high levels Indian Hedgehog identified its downstream target as stromal GLI1+...
Abstract Despite advances in the development of highly effective androgen receptor (AR)-directed therapies for treatment men with advanced prostate cancer, acquired resistance to such frequently ensues. A significant subset patients resistant disease develop AR-negative tumors that lose their luminal identity and display neuroendocrine features (neuroendocrine cancer (NEPC)). The cellular heterogeneity molecular evolution during progression from AR-positive adenocarcinoma NEPC has yet be...
Obesity, defined as a body mass index (BMI) ≥ 30, is an established risk factor for breast cancer among women in the general population after menopause. Whether elevated BMI with germline mutation BRCA1 or BRCA2 less clear because of inconsistent findings from epidemiological studies and lack mechanistic this population. Here, we show that DNA damage normal epithelia carrying BRCA positively correlated biomarkers metabolic dysfunction. In addition, RNA sequencing showed obesity-associated...
Abstract The outer blood-retina barrier is established through the coordinated terminal maturation of retinal pigment epithelium (RPE), fenestrated choroid endothelial cells (ECs) and Bruch’s membrane, a highly organized basement membrane that lies between both cell types. Here we study contribution ECs to this process by comparing their gene expression profile before (P5) after (P30) critical postnatal period when mice acquire mature visual function. Transcriptome analyses show...
Obesity is associated with adipose inflammation, defined by macrophages encircling dead adipocytes, as well extracellular matrix (ECM) remodeling and increased risk of breast cancer. Whether ECM affects macrophage phenotype in obesity uncertain. A better understanding this relationship could be strategically important to reduce cancer or improve outcomes the obese. Using clinical samples, computational approaches, vitro decellularized models, study quantified relative abundance...
Abstract Expression of the DNA/RNA helicase schlafen family member 11 (SLFN11) has been identified as a sensitizer tumor cells to DNA-damaging agents including platinum chemotherapy. We assessed impact SLFN11 expression on response chemotherapy and outcomes in patients with metastatic castration-resistant prostate cancer (CRPC). Tumor was 41 CRPC treated by RNA sequencing (RNA-seq) biopsy tissue (n = 27) and/or immunofluorescence circulating (CTC; n 20). Cox regression Kaplan–Meier methods...
Abstract Tumor heterogeneity is common in cancer, however recent studies have applied single gene expression signatures to classify bladder cancers into distinct subtypes. Such stratification assumes that a predominant transcriptomic signature sufficient predict progression kinetics, patient survival and treatment response. We hypothesize such static classification ignores intra-tumoral the potential for cellular plasticity occurring during disease development. conducted cell transcriptome...
Thyroid cancer is common, yet the sequence of alterations that promote tumor formation are incompletely understood. Here, we describe a novel model thyroid carcinoma in zebrafish reveals temporal changes due to BRAF V600E . Through use real-time vivo imaging, observe disruption follicle structure occurs early development. Combinatorial treatment using and MEK inhibitors reversed developmental effects induced by Adult expressing thyrocytes developed invasive carcinoma. We identified gene...
BACKGROUND Metastatic biopsies are increasingly being performed in patients with advanced prostate cancer to search for actionable targets and/or identify emerging resistance mechanisms. Due a predominance of bone metastases and their sclerotic nature, obtaining sufficient tissue clinical genomic studies is challenging. METHODS Patients were enrolled between February 2013 March 2017 on an institutional review board‐approved protocol prospective image‐guided biopsy. Bone blood clots collected...
Summary BCR / ABL 1 ‐like acute lymphoblastic leukaemia ( ALL ) is a subgroup of B‐lineage that occurs within cases without recurrent molecular rearrangements. Gene expression profiling GEP can identify these but it expensive and not widely available. Using , we identified 10 genes specifically overexpressed by used their values – assessed quantitative real time‐polymerase chain reaction (Q‐ RT ‐ PCR in 26 non‐ to build statistical “ predictor”, for the identification cases. By screening 142...
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive malignancy that occurs in young women, characterized by recurrent loss-of-function mutations SMARCA4 gene, and for which effective treatments options are lacking. The aim this study was to broaden knowledge on rare reporting a comprehensive molecular analysis independent cohort SCCOHT cases. We conducted Whole Exome Sequencing six SCCOHT, RNA-sequencing array comparative genomic hybridization eight SCCOHT....
Following treatment with androgen receptor (AR) pathway inhibitors, ≈20% of prostate cancer patients progress by shedding their AR-dependence. These tumors undergo epigenetic reprogramming turning castration-resistant adenocarcinoma (CRPC-Adeno) into neuroendocrine (CRPC-NEPC). No targeted therapies are available for CRPC-NEPCs, and there minimal organoid models to discover new therapeutic targets against these aggressive tumors. Here, using a combination patient tumor proteomics, RNA...
Abstract Purpose: Patients with neuroendocrine prostate cancer (NEPC) are often managed immunotherapy regimens extrapolated from small-cell lung (SCLC). We sought to evaluate the tumor immune landscape of NEPC compared other types and SCLC. Experimental Design: In this retrospective study, a cohort 170 patients 230 RNA-sequencing 104 matched whole-exome sequencing data were analyzed. Differences in stromal constituents, frequency genomic alterations, associations outcomes evaluated. Results:...
Patients with cancer who graciously consent for autopsy represent an invaluable resource the study of biology. To advance tumor evolution, metastases, and resistance to treatment, we developed a next-generation rapid program integrated within broader precision medicine clinical trial that interrogates pre- postmortem tissue samples patients all ages types.
We developed a precision medicine program for patients with advanced cancer using integrative whole-exome sequencing and transcriptome analysis.Five hundred fifteen locally advanced/metastatic solid tumors were prospectively enrolled, paired tumor/normal was performed. Seven fifty-nine from 515 evaluated.Most frequent tumor types prostate (19.4%), brain (16.5%), bladder (15.4%), kidney (9.2%). Most frequently altered genes TP53 (33%), CDKN2A (11%), APC (10%), KTM2D (8%), PTEN BRCA2 (8%)....