A5088667874- Prostate Cancer Treatment and Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- Protein Tyrosine Phosphatases
- Radiopharmaceutical Chemistry and Applications
- Radiomics and Machine Learning in Medical Imaging
- Bioactive Compounds and Antitumor Agents
- Molecular Biology Techniques and Applications
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- Computational Drug Discovery Methods
- Cytokine Signaling Pathways and Interactions
- Papaya Research and Applications
- Genomics and Chromatin Dynamics
- Cancer-related Molecular Pathways
- Synthesis of Indole Derivatives
- Peroxisome Proliferator-Activated Receptors
- Machine Learning in Bioinformatics
- Cancer Research and Treatments
- Polyamine Metabolism and Applications
Cold Spring Harbor Laboratory
2016-2025
Stony Brook University
2023-2025
New York Hospital Queens
2014
Dana-Farber Cancer Institute
2014
NewYork–Presbyterian Hospital
2014
Cornell University
2014
University of Michigan–Ann Arbor
2014
Icahn School of Medicine at Mount Sinai
2014
University of California, San Diego
2014
Saint John's Health Center
2013
Waking up in a trap Cancer patients who have undergone successful treatment can experience relapse of their disease years or even decades later. This is because cancer cells that disseminated beyond the primary tumor site enter state dormancy, where they remain viable but not proliferating. Eventually, by mechanisms are poorly understood, these clinically undetectable “wake up” and form actively growing metastases. Studying mouse models, Albrengues et al. found sustained lung inflammation...
Huntington's disease (HD) is characterized by the accumulation of a pathogenic protein, Huntingtin (Htt), that contains an abnormal polyglutamine expansion. Here, we report fragment Htt (Httex1p) can be modified either small ubiquitin-like modifier (SUMO)–1 or ubiquitin on identical lysine residues. In cultured cells, SUMOylation stabilizes Httex1p, reduces its ability to form aggregates, and promotes capacity repress transcription. Drosophila model HD, Httex1p exacerbates neurodegeneration,...
Complete inactivation of the PTEN tumor suppressor gene is extremely common in advanced cancer, including prostate cancer (CaP). However, one allele already lost vast majority CaPs at presentation. To determine consequence dose variations on progression, we have generated by homologous recombination a hypomorphic Pten mouse mutant series with decreasing activity: Ptenhy/+ > Pten+/− Ptenhy/− (mutants which rescued embryonic lethality due to complete inactivation) conditional knockout (Ptenpc)...
Irreversible cell growth arrest, a process termed cellular senescence, is emerging as an intrinsic tumor suppressive mechanism. Oncogene-induced senescence thought to be invariably preceded by hyperproliferation, aberrant replication, and activation of DNA damage checkpoint response (DDR), rendering therapeutic enhancement this unsuitable for cancer treatment. We previously demonstrated in mouse model prostate that inactivation the suppressor phosphatase tensin homolog deleted on chromosome...
Cellular senescence can exert dual effects in tumors, either suppressing or promoting tumor progression. The senescence-associated secretory phenotype (SASP), released by senescent cells, plays a crucial role this dichotomy. Consequently, the clinical challenge lies developing therapies that safely enhance cancer, favoring tumor-suppressive SASP factors over tumor-promoting ones. Here, we identify retinoic-acid-receptor (RAR) agonist adapalene as an effective pro-senescence compound prostate...
Summary: The field of cancer neuroscience has begun to define the contributions nerves initiation and progression; here, we highlight future directions basic translational for malignancies arising outside central nervous system.
Abstract The CRISPR/Cas9 system is a powerful tool for studying gene function. Here, we describe method that allows temporal control of activity based on conditional Cas9 destabilization. We demonstrate fusing an FKBP12-derived destabilizing domain to (DD-Cas9) enables expression and editing in the presence FKBP12 synthetic ligand. This can be easily adapted co-express, from same promoter, DD-Cas9 with any other interest without co-modulation latter. In particular, when co-expressed...
Highlights•A screen identifies complex I inhibitors as highly selective against Pten-null cells•Pten-null selectivity is unmatched by common standard of care chemotherapy agents•Mitochondria cells easily switch to consuming ATP instead producing it•The inhibitor deguelin can suppress lethal prostate cancer in RapidCaPSummaryA hallmark advanced (PC) the concomitant loss PTEN and p53 function. To selectively eliminate such cells, we screened cytotoxic compounds on Pten−/−;Trp53−/− fibroblasts...
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, and new therapies are needed. Altered metabolism is cancer vulnerability, several metabolic pathways have been shown to promote PDAC. However, the changes in cholesterol their role during PDAC progression remain largely unknown. Here we used organoid mouse models determine drivers of altered consequences its disruption on tumor progression. We identified sterol O-acyltransferase 1 (SOAT1) as key player sustaining mevalonate...
PTEN (phosphatase and tensin homologue deleted on chromosome TEN) is the major negative regulator of phosphatidylinositol 3-kinase signaling has cell-specific functions including tumor suppression. Nuclear localization vital for suppression; however, outside cancer, molecular physiological events driving nuclear entry are unknown. In this paper, we demonstrate that cytoplasmic Pten was translocated into nuclei neurons after cerebral ischemia in mice. Critically, transport event dependent a...
Genetically engineered mouse (GEM) models are a pillar of functional cancer research. Here, we developed RapidCaP, GEM modeling system that uses surgical injection for viral gene delivery to the prostate. We show in Pten deficiency, loss p53 suffices trigger metastasis distant sites at greater than 50% penetrance by four months, consistent with results from human prostate genome analysis. Live bioluminescence tracking showed endogenous primary and metastatic disease responds castration...
The androgen receptor (AR) signaling axis plays a key role in the pathogenesis of prostate cancer. In this study, we found that protein tyrosine phosphatase PTP1B, well-established regulator metabolic signaling, was induced after stimulation AR-expressing cancer cells. PTP1B induction by occurred at mRNA and levels to increase activity. High-resolution chromosome mapping revealed AR recruitment two response elements within first intron encoding gene PTPN1, correlating with an AR-mediated RNA...
We have recently recapitulated metastasis of human PTEN/TP53-mutant prostate cancer in the mouse using RapidCaP system. Surprisingly, we found that this is driven by MYC, and not AKT, activation. Here, show cell-cell communication IL6 drives AKT-MYC switch through activation AKT-suppressing phosphatase PHLPP2, when PTEN p53 are lost together, but separately. then communicates a downstream program STAT3-mediated MYC activation, which cell proliferation. Similarly, tissues, peak proliferation...
Abstract Purpose: Napabucasin (2-acetylfuro-1,4-naphthoquinone or BBI-608) is a small molecule currently being clinically evaluated in various cancer types. It has mostly been recognized for its ability to inhibit STAT3 signaling. However, based on chemical structure, we hypothesized that napabucasin substrate intracellular oxidoreductases and therefore may exert anticancer effect through redox cycling, resulting reactive oxygen species (ROS) production cell death. Experimental Design:...