A5044821126- Prostate Cancer Treatment and Research
- Bioinformatics and Genomic Networks
- Computational Drug Discovery Methods
- Cancer, Lipids, and Metabolism
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- FOXO transcription factor regulation
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Estrogen and related hormone effects
- Cell Adhesion Molecules Research
- Steroid Chemistry and Biochemistry
- Prostate Cancer Diagnosis and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related gene regulation
- Protein Degradation and Inhibitors
- Hippo pathway signaling and YAP/TAZ
- Microbial Metabolic Engineering and Bioproduction
- Mathematical Biology Tumor Growth
- Maternal and Perinatal Health Interventions
- Bone health and treatments
- Privacy-Preserving Technologies in Data
- Genomic variations and chromosomal abnormalities
- Preterm Birth and Chorioamnionitis
Rutgers Cancer Institute of New Jersey
2020-2024
Rutgers, The State University of New Jersey
2005-2024
Weatherford College
2023
Rutgers Sexual and Reproductive Health and Rights
2023
Rutgers Health
2017-2022
Columbia University
2011-2022
Columbia University Irving Medical Center
2012-2018
New Jersey Department of Health
2018
Herbert Irving Comprehensive Cancer Center
2012-2013
Center for Systems Biology
2013
Current treatments for castration-resistant prostate cancer (CRPC) that target androgen receptor (AR) signaling improve patient survival, yet ultimately fail. Here, we provide novel insights into treatment response the antiandrogen abiraterone by analyses of a genetically engineered mouse (GEM) model with combined inactivation
Significance Although locally invasive prostate cancer is nearly always curable, metastatic usually results in lethality. Our study investigates the temporal progression and molecular mechanisms underlying metastasis using a new genetically engineered mouse model. Using lineage-tracing analyses, we show that dissemination of tumor cells occurs early progression, well before occurrence metastases. We further temporally coincident with expression oncogenic ETS gene Etv4 , promotes vivo....
The NKX3.1 homeobox gene plays essential roles in prostate differentiation and cancer. We show that loss of function Nkx3.1 mouse results down-regulation genes are for differentiation, as well up-regulation not normally expressed prostate. Conversely, gain an otherwise fully differentiated nonprostatic epithelium (seminal vesicle) is sufficient respecification to renal grafts vivo. In human cells, these activities require the interaction with G9a histone methyltransferase via homeodomain...
Deciphering cell-intrinsic mechanisms of metastasis progression in vivo is essential to identify novel therapeutic approaches. Here we elucidate drivers metastatic prostate cancer through analyses genetically engineered mouse models (GEMM) and correlative studies human cancer. Expression profiling lineage-marked cells from primary tumors metastases defines a signature de novo progression. Cross-species master regulator comparing this with comparable identifies conserved demonstrable clinical...
Abstract Heterogeneous response to Enzalutamide, a second-generation androgen receptor signaling inhibitor, is central problem in castration-resistant prostate cancer (CRPC) management. Genome-wide systems investigation of mechanisms that govern Enzalutamide resistance promise elucidate markers heterogeneous treatment and salvage therapies for CRPC patients. Focusing on the de novo role MYC as marker resistance, here we reconstruct CRPC-specific mechanism-centric regulatory network,...
Both the PI3K → Akt mTOR and mitogen-activated protein kinase (MAPK) signaling pathways are often deregulated in prostate tumors with poor prognosis. Here we describe a new genetically engineered mouse model of cancer which PI3K-Akt-mTOR is activated by inducible disruption PTEN, extracellular signal-regulated 1/2 (ERK1/2) MAPK expression BRAF(V600E) oncogene. These tissue-specific compound mutant mice develop lethal that inherently resistant to castration. bypass cellular senescence...
Although the prognosis for clinically localized prostate cancer is now favorable, there are still no curative treatments castration-resistant (CRPC) and, therefore, it remains fatal. In this study, we investigate a new therapeutic approach treatment of CRPC, which involves dual targeting major signaling pathway that frequently deregulated in disease. We found Akt and mTOR pathways with their respective inhibitors, MK-2206 ridaforolimus (MK-8669), highly effective inhibiting CRPC preclinical...
Mitochondria provide the first line of defense against tumor-promoting effects oxidative stress. Here we show that prostate-specific homeoprotein NKX3.1 suppresses prostate cancer initiation by protecting mitochondria from Integrating analyses genetically engineered mouse models, human cells, and organotypic cultures, find that, in response to stress, is imported via chaperone protein HSPA9, where it regulates transcription mitochondrial-encoded electron transport chain (ETC) genes, thereby...
Abstract Prioritizing treatments for individual patients with cancer remains challenging, and performing coclinical studies using patient-derived models in real time is often unfeasible. To circumvent these challenges, we introduce OncoLoop, a precision medicine framework that predicts drug sensitivity human tumors their preexisting high-fidelity (cognate) model(s) by leveraging perturbation profiles. As proof of concept, applied OncoLoop to prostate genetically engineered mouse (GEMM)...
Although genetically engineered mouse (GEM) models are often used to evaluate cancer therapies, extrapolation of such preclinical data human can be challenging. Here, we introduce an approach that uses drug perturbation from GEM predict efficacy in cancer. Network-based analysis expression profiles vivo treatment identified drugs and combinations inhibit the activity FOXM1 CENPF, which master regulators prostate malignancy. Validation confirmed specificity synergy a predicted combination...
Master regulatory genes of tissue specification play key roles in stem/progenitor cells and are often important cancer. In the prostate, androgen receptor (AR) is a master regulator essential for development tumorigenesis, but its specific functions prostate have not been elucidated. We investigated AR function CARNs (CAstration-Resistant Nkx3.1-expressing cells), luminal cell that regeneration. Using genetically--engineered mouse models novel epithelial lines, we find progenitor properties...
BackgroundPrioritization of breast cancer patients based on the risk resistance to tamoxifen plays a significant role in personalized therapeutic planning and improving disease course outcomes.MethodsIn this work, we demonstrate that genome-wide pathway-centric computational framework elucidates molecular pathways as markers ER+ patients. In particular, associated activity levels with wide spectrum response tamoxifen, which defined cancer.FindingsWe identified five biological failure...
High-risk pediatric B-ALL patients experience 5-year negative event rates up to 25%. Although some biomarkers of relapse are utilized in the clinic, their ability predict outcomes high-risk is limited. Here, we propose a random survival forest (RSF) machine learning model utilizing interpretable genomic inputs relapse/death patients. We whole exome sequencing profiles from 156 TARGET-ALL study (with samples collected at presentation) further stratified into training and test cohorts (109 47...
To date, reprogramming strategies for generating cell types of interest have been facilitated by detailed understanding relevant developmental regulatory factors. However, identification such drivers often represents a major challenge, as specific gene combinations may be required reprogramming. Here we show that computational systems approach can identify type specification genes (master regulators) act synergistically, and demonstrate its application fibroblasts to prostate tissue. We use...
Great effort is spent on developing therapies to improve the dire outcomes of those diagnosed with acute myeloid leukemia. The methods for quantifying response therapeutic intervention have however lacked sensitivity. Patients achieving a complete remission as defined by conventional cytomorphological therefore remain at risk subsequent relapse due disease persistence. Improved stratification possible based tests designed detect this residual leukemic burden (measurable disease). However,...
ABSTRACT Although it is known that inflammation plays a critical role in prostate tumorigenesis, the underlying processes are not well understood. Based on analysis of genetically engineered mouse models combined with correlative expression profiling data from human tumors, we demonstrate reciprocal relationship between and status NKX3.1 homeobox gene associated cancer initiation. We find initiation aged Nkx3.1 mutant mice correlates enrichment specific immune populations increased...
Accurate computational prediction of protein functions increasingly relies on network-inspired models for the function transfer. This task can become challenging proteins isolated in their own network or those with poor uncharacterized neighborhoods. Here, we present a novel probabilistic chain-graph-based approach predicting that builds connecting networks two (or more) different species by links high interspecies sequence homology. In this way, are able to "exchange" functional information...
Some prostate cancers (PCas) are histo-pathologically grouped within the same Gleason Grade (GG), but can differ significantly in outcome. Herein, we aimed at identifying molecular biomarkers that could improve risk prediction PCa. LC ESI-MS/MS was performed on human PCa and benign prostatic hyperplasia (BPH) tissues peptide data integrated with omic analyses. We identified high YWHAZ NDRG1 expression to be associated poor prognosis considering all scores (GS). defined two subpopulations of...