A5083552566- Cancer, Lipids, and Metabolism
- Prostate Cancer Treatment and Research
- Advanced Breast Cancer Therapies
- Lung Cancer Research Studies
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- RNA modifications and cancer
- Cancer-related gene regulation
- Lung Cancer Treatments and Mutations
- PARP inhibition in cancer therapy
- Cancer, Hypoxia, and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Cancer-related molecular mechanisms research
- Ocular Oncology and Treatments
- Cancer Mechanisms and Therapy
- Eicosanoids and Hypertension Pharmacology
- RNA Research and Splicing
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Gold and Silver Nanoparticles Synthesis and Applications
- Neuroendocrine Tumor Research Advances
- Cardiac Fibrosis and Remodeling
- Estrogen and related hormone effects
Dana-Farber Cancer Institute
2019-2025
Harvard University
2022-2024
Pediatrics and Genetics
2008-2023
Stanford Medicine
2023
Brigham and Women's Hospital
2022
University of Cambridge
2014-2020
Deborah Heart and Lung Center
2019
UCSF Helen Diller Family Comprehensive Cancer Center
2010
University of California, San Francisco
2010
Stanford University
2008
The two oncogenes KRas and Myc cooperate to drive tumorigenesis, but the mechanism underlying this remains unclear. In a mouse lung model of
Small-cell lung carcinoma (SCLC) is a neuroendocrine subtype of cancer. Although SCLC patients often initially respond to therapy, tumors nearly always recur, resulting in 5-year survival rate less than 10%. A mouse model has been developed based on the fact that RB and p53 tumor suppressor genes are mutated more 90% human SCLCs. Emerging evidence models suggests p130, gene related RB, may act as cells. To test this idea, we used conditional mutant mice delete p130 combination with Rb adult...
Abstract Members of the family RAS proto-oncogenes, discovered just over 40 years ago, were among first cancer-initiating genes to be discovered. Of three members, KRAS is most frequently mutated in human cancers. Despite intensive biological and biochemical study proteins past four decades, we are only now starting devise therapeutic strategies target their oncogenic properties. Here, highlight distinct properties common rare alleles, enabling classification into functional subtypes. We...
MYC-mediated pathogenesis in lung cancer continues to attract interest for new therapeutic strategies. In this study, we describe a transgenic mouse model of KRAS-driven adenocarcinoma that affords reversible activation MYC, used here as tool lipidomic profiling MYC-dependent tumors formed model. Advanced mass spectrometric imaging and surface analysis techniques were characterize the spatial temporal changes lipid composition tissue. We found normal tissue was characterized predominantly by...
Abstract Lineage transitions are a central feature of prostate development, tumourigenesis and treatment resistance. While epigenetic changes well known to drive lineage transitions, it remains unclear how upstream metabolic signalling contributes the regulation epithelial identity. To fill this gap, we developed an approach perform metabolomics on primary cells. Using approach, discovered that basal luminal cells exhibit distinct metabolomes nutrient utilization patterns. Furthermore,...
Abstract It is unclear why some tissues are refractory to the mitogenic effects of oncogene Myc. Here we show that Myc activation induces rapid transcriptional responses followed by proliferation in some, but not all, organs. Despite such disparities proliferative response, bound DNA at open elements responsive (liver) and non-responsive (heart) tissues, fails induce a robust response heart. Using heart as an exemplar tissue, Myc-driven transcription re-engaged mature cardiomyocytes...
In the field of optical imaging, ability to image tumors at depth with high selectivity and specificity remains a challenge. Surface enhanced resonance Raman scattering (SERRS) nanoparticles (NPs) can be employed as contrast agents specifically target cells in vivo; however, this technique typically requires time-intensive point-by-point acquisition spectra. Here, we combine use "spatially offset spectroscopy" (SORS) that SERRS known "surface spatially (SESORRS) deep-seated vivo....
Nonsmall cell lung cancer (NSCLC) is a leading cause of cancer-related deaths. While mutations in Kras and overexpression Myc are commonly found patients, the role altered lipid metabolism its interplay with oncogenic poorly understood. Here we use transgenic mouse model Kras-driven adenocarcinoma reversible activation combined surface analysis profiling tumors transcriptomics to study effect activity on cholesterol homeostasis. Our findings reveal that leads accumulation cholesteryl esters...
In cancer cells, the retinoblastoma tumor suppressor RB is directly inactivated by mutation in gene or functionally inhibited abnormal activation of cyclin-dependent kinase activity. While variations levels may also provide an important means controlling function both normal and little known about mechanisms regulating transcription. Here we show that members E2F families bind to promoter. To investigate how RB/E2F pathway regulate Rb transcription, generated reporter mice carrying eGFP...
Epidermal growth factor receptor (Egfr)-driven signaling regulates fundamental homeostatic processes. Dysregulated via Egfr is implicated in numerous disease pathologies and distinct Egfr-associated etiologies are known to be tissue-specific. The molecular basis of this tissue-specificity remains poorly understood. Most studies date have been performed vitro or tissue-specific mouse models disease, which has limited insight into patterns healthy tissues. Here, we carried out integrated...
<p>Summary of Peak calls following H3K27ac ChIPseq with Atacseq integration.</p>
<p>Supplement Figure 2. A. SKO, DKO, and PPKO were cultured as 3-dimensional spheroids treated with the indicated concentrations of CDK2 inhibitor - BGG463 over 72 hours. Cell growth was determined by CellTiter-Glo luminescent cell viability assay. B. Western blot analysis for Cdk2, Cdk5, Vinculin following DKO concentration PROTAC CPS2. Full western membranes C) CDK2, D) CDK5, E) vinculin.</p>
<p>A. Full membrane following CRISPR targeting of Mybl2 indicating specific our target gene. B. DKO-Ctl and DKO-Mybl2 KO cells were cultured as 2-dimensional monolayers overall cell growth was determined by CellTiter-Glo luminescent viability assay.</p>
<p>Combined genes enriched in human NEPC, PDX samples and NE-like mouse models</p>
<p>DEG analysis between DKO Mybl2 KO versus Ctl cells and PPKO Ctl</p>
The retinoblastoma tumor suppressor (Rb) is a potent and ubiquitously expressed cell cycle regulator, but patients with germline Rb mutation develop very specific spectrum. This surprising observation raises the possibility that mechanisms compensate for loss of function are present or activated in many types. In particular, p107, protein related to Rb, has been shown functionally overlap several cellular contexts. To investigate underlying this functional redundancy between p107 vivo, we...
Phenotypic plasticity is a recognized mechanism driving therapeutic resistance in patients with prostate cancer. Although underlying molecular causations phenotypic have been identified, success yet to be achieved. To identify putative master regulator transcription factors (MR-TF) cancer, this work utilized multiomic approach using genetically engineered mouse models of cancer combined patient data MYB proto-oncogene like 2 (MYBL2) as significantly enriched factor exhibiting plasticity....
Phenotypic plasticity is a recognized mechanism driving therapeutic resistance in prostate cancer (PCa) patients. While underlying molecular causations phenotypic have been identified, success yet to be achieved. To identify putative master regulator transcription factors (MR-TF) PCa, this work utilized multiomic approach using genetically engineered mouse models of combined with patient data MYBL2 as significantly enriched factor PCa exhibiting plasticity. Genetic inhibition
AbstractThe RB tumor suppressor gene is mutated in a broad range of human cancers, including pediatric retinoblastoma. Strikingly, however, Rb mutant mice develop tumors the pituitary and thyroid glands, but not Mouse genetics experiments have demonstrated that p107, protein related to pRB, capable preventing retinoblastoma, tumors, Rb-deficient mice. Evidence suggests basis for this compensatory function p107 increased transcription response inactivation. To begin address context-dependency...
Abstract While genetically engineered mice have made an enormous contribution towards the elucidation of human disease, it has hitherto not been possible to tune up or down level expression any endogenous gene. Here we describe compound modified in which E2f3 gene may be either reversibly elevated repressed adult animals by oral administration tetracycline. This technology is, principle, applicable gene, allowing direct determination both and reduced physiological pathological processes....
Abstract Prostate cancers are considered immunologically ‘cold’ tumors given the very few patients who respond to checkpoint inhibitor therapy (CPI). Recently, enrichment of interferon (IFN) response genes predicts a favorable CPI across various disease sites. The enhancer zeste homolog-2 (EZH2) is over-expressed in prostate cancer and known negatively regulate IFN genes. Here, we demonstrate that inhibition EZH2 catalytic activity models derepresses expression double-strand RNA (dsRNA),...
Chemoprevention trials for prostate cancer by androgen receptor or synthesis inhibition have proven ineffective. Recently, it has been demonstrated that the histone methlytransferase, EZH2 is deregulated in mouse and human high-grade prostatic intraepithelial neoplasia (HG-PIN). Using preclinical models of cancer, we demonstrate genetic chemical disruption expression catalytic activity reversed HG-PIN phenotype. Furthermore, function was associated with loss cellular proliferation induction...