A5012185374- Cancer, Lipids, and Metabolism
- Cancer-related Molecular Pathways
- Cancer, Hypoxia, and Metabolism
- Prostate Cancer Treatment and Research
- DNA Repair Mechanisms
- Lung Cancer Treatments and Mutations
- Ubiquitin and proteasome pathways
- Glioma Diagnosis and Treatment
- PARP inhibition in cancer therapy
- Mass Spectrometry Techniques and Applications
- Advanced Breast Cancer Therapies
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- DNA and Nucleic Acid Chemistry
- Acute Myeloid Leukemia Research
- Retinoids in leukemia and cellular processes
- Cancer therapeutics and mechanisms
- Microtubule and mitosis dynamics
- Genetic factors in colorectal cancer
- Gene expression and cancer classification
- Genomics and Chromatin Dynamics
- Molecular Biology Techniques and Applications
- Cell Adhesion Molecules Research
- Circadian rhythm and melatonin
Thomas Jefferson University
2016-2023
Sidney Kimmel Cancer Center
2017-2023
Marist College
2015
The tumor suppressor protein retinoblastoma (RB) is mechanistically linked to suppression of transcription factor E2F1-mediated cell cycle regulation. For multiple types, loss RB function associated with poor clinical outcome. action abrogated either by direct depletion or through inactivation function; however, the basis for this selectivity unknown. Here, analysis samples and cell-free DNA from patients advanced prostate cancer showed that was preferred pathway disruption in human disease....
Abstract Mechanisms regulating DNA repair processes remain incompletely defined. Here, the circadian factor CRY1, an evolutionally conserved transcriptional coregulator, is identified as a tumor specific regulator of repair. Key findings demonstrate that CRY1 expression androgen-responsive and associates with poor outcome in prostate cancer. Functional studies first-in-field mapping cistrome transcriptome reveal regulates G2/M transition. damage stabilizes cancer (in vitro, vivo, human...
Abstract Loss of the retinoblastoma (RB) tumor suppressor protein is a critical step in reprogramming biological networks that drive cancer progression, although mechanistic insight has been largely limited to impact RB loss on cell-cycle regulation. Here, isogenic modeling identified disease stage–specific rewiring E2F1 function, providing first-in-field mapping cistrome and transcriptome after across progression. Biochemical functional assessment using both vitro vivo models an unexpected,...
Research Article22 November 2018Open Access Source DataTransparent process PARP-1 regulates DNA repair factor availability Matthew J Schiewer Corresponding Author [email protected] Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA Sidney Kimmel Center, Search for more papers by this author Amy C Mandigo Nicolas Gordon Fangjin Huang Cedars-Sinai Medical Los Angeles, CA, Sanchaika Gaur Renée de Leeuw Shuang G Zhao Radiation Oncology, University Michigan, Ann...
Emerging evidence indicates the deubiquitinase USP22 regulates transcriptional activation and modification of target substrates to promote pro-oncogenic phenotypes. Here,
Abstract The tumor suppressor gene TP53 is the most frequently mutated in numerous cancer types, including prostate (PCa). Specifically, missense mutations are selectively enriched PCa, and cluster to particular “hot spots” p53 DNA binding domain with mutation at R273 residue occurring frequently. While this similarly R273C-p53 or R273H-p53 all types examined, PCa selective enrichment of observed. Importantly, examination clinical datasets indicated that heterozygosity can either be...
DNA-dependent protein kinase catalytic subunit (DNA-PK) is a pleiotropic involved in DNA repair and transcriptional regulation. DNA-PK deregulated selected cancer types strongly associated with poor outcome. The underlying mechanisms by which promotes aggressive tumor phenotypes are not well understood. Here, unbiased molecular investigation clinically relevant models reveals novel functions of cancer.Experimental Design: function was modulated using both genetic pharmacologic methods series...
Abstract Purpose: DNA-dependent protein kinase catalytic subunit (DNA-PKcs, herein referred as DNA-PK) is a multifunctional of high cancer relevance. DNA-PK deregulated in multiple tumor types, including prostate cancer, and associated with poor outcomes. was previously nominated therapeutic target inhibitors are currently undergoing clinical investigation. Although well studied DNA repair transcriptional regulation, much remains to be understood about the way by which drives aggressive...
Neuroendocrine prostate cancer (NEPrCa) arises de novo or after accumulation of genomic alterations in pre-existing adenocarcinoma tumors response to androgen deprivation therapies. We have provided evidence that small extracellular vesicles released by PrCa cells and containing the αVβ3 integrin promote neuroendocrine differentiation vivo vitro . Here, we examined expression three murine models carrying a deletion PTEN (SKO), RB1 (DKO), , TRP53 (TKO) genes prostatic epithelium; these...
Abstract The retinoblastoma tumor suppressor (RB) is a critical regulator of E2F-dependent transcription, controlling multitude protumorigenic networks including but not limited to cell-cycle control. Here, genome-wide assessment E2F1 function after RB loss in isogenic models prostate cancer revealed unexpected repositioning and cooperation with oncogenic transcription factors, the major driver disease progression, androgen receptor (AR). Further investigation that observed AR/E2F1 elicited...
Abstract Prostate cancer (PCa) is the second leading cause of death for men in United States. While organ-confined disease has reasonable expectation cure, metastatic PCa universally fatal upon recurrence during hormone therapy, a stage termed castration-resistant prostate (CRPC). Until such time as molecularly defined subtypes can be identified and targeted using precision medicine, it necessary to investigate new therapies that may apply CRPC population whole. The administration ascorbate,...
Abstract PARP1 holds two major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context cancer. Notably, has been found to be a key modulator androgen receptor (AR) function AR-dependent phenotypes, is driving factor prostate cancer (PCa) biology therapeutic management. Recent studies indicate an unanticipated prevalence alterations advanced PCa showed that inhibitors (PARPi) can effectively manage subset these tumors. Despite having...
269 Background: PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context cancer. Previously, it was determined that ins involved regulation androgen receptor activity. Methods: Here, unbiased profiling revealed downstream profile enzymatic activity.Results: Further investigation PARP-1-regulated transcriptome secondary strategies for assessing activity patient tissues unexpectedly enriched as a function disease...
189 Background: There is emergent and compelling evidence to support RB status as a biomarker in advanced prostate cancer. loss strongly associated with poor progression-free, disease-specific, overall survival cancer (PCa). Preclinical studies PCa have revealed positive tumors are more responsive CDK4/6 inhibitors. An ongoing randomized Phase IB/II study of enzalutamide without ribociclib patients metastatic castration-resistant, chemotherapy naïve has become pioneer trial include inclusion...
Abstract Prostate cancer (PCa) is the most frequently diagnosed non-cutaneous malignancy, and second leading cause of death in males United States, causing over 30,000 deaths per year. A crucial component to development progression PCa activity androgen receptor (AR). AR promotes proliferation required for cell growth survival. As such, targeting AR-signaling axis through deprivation therapy (ADT) first line PCa. However, cells invariably become resistant this men relapse with incurable form...
<p>Supplementary Figures 1-6</p>
<p>Supplementary Figures 1-6</p>
<div>AbstractPurpose:<p>DNA-dependent protein kinase catalytic subunit (DNA-PK) is a pleiotropic involved in DNA repair and transcriptional regulation. DNA-PK deregulated selected cancer types strongly associated with poor outcome. The underlying mechanisms by which promotes aggressive tumor phenotypes are not well understood. Here, unbiased molecular investigation clinically relevant models reveals novel functions of cancer.</p><p><b>Experimental...
<div>AbstractPurpose:<p>DNA-dependent protein kinase catalytic subunit (DNA-PK) is a pleiotropic involved in DNA repair and transcriptional regulation. DNA-PK deregulated selected cancer types strongly associated with poor outcome. The underlying mechanisms by which promotes aggressive tumor phenotypes are not well understood. Here, unbiased molecular investigation clinically relevant models reveals novel functions of cancer.</p><p><b>Experimental...
<div>Abstract<p>Emerging evidence indicates the deubiquitinase USP22 regulates transcriptional activation and modification of target substrates to promote pro-oncogenic phenotypes. Here, <i>in vivo</i> characterization tumor-associated upregulation unbiased interrogation USP22-regulated functions vitro</i> demonstrated critical roles for in prostate cancer. Specifically, clinical datasets validated that expression is elevated cancer, a novel murine model...