A5073428129- Prostate Cancer Treatment and Research
- Computational Drug Discovery Methods
- Cancer, Lipids, and Metabolism
- Melanoma and MAPK Pathways
- Click Chemistry and Applications
- Protein Degradation and Inhibitors
- Prostate Cancer Diagnosis and Treatment
- Synthesis and biological activity
- PI3K/AKT/mTOR signaling in cancer
- Cancer Genomics and Diagnostics
- Chronic Lymphocytic Leukemia Research
- RNA modifications and cancer
- T-cell and B-cell Immunology
- Cancer-related Molecular Pathways
- Estrogen and related hormone effects
- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Food Allergy and Anaphylaxis Research
- Peptidase Inhibition and Analysis
- PARP inhibition in cancer therapy
- Epigenetics and DNA Methylation
- Hippo pathway signaling and YAP/TAZ
- Ubiquitin and proteasome pathways
- Steroid Chemistry and Biochemistry
- RNA Research and Splicing
National Institutes of Health
2019-2025
National Cancer Institute
2020-2024
Center for Cancer Research
2019-2024
Cancer Institute (WIA)
2019-2022
Beth Israel Deaconess Medical Center
2021
Harvard University
2021
University of Virginia
2012-2020
University of Virginia Health System
2014-2019
Virginia Commonwealth University Medical Center
2016
Johns Hopkins University
2014
Designer Chromosome One of the ultimate aims synthetic biology is to build designer organisms from ground up. Rapid advances in DNA synthesis has allowed assembly complete bacterial genomes. Eukaryotic organisms, with their generally much larger and more complex genomes, present an additional challenge biologists. Annaluru et al. (p. 55 , published online 27 March) designed a eukaryotic chromosome based on yeast III. The chromosome, shorn destabilizing transfer RNA genes transposons, ∼14%...
Patients diagnosed with high risk localized prostate cancer have variable outcomes following surgery. Trials of intense neoadjuvant androgen deprivation therapy (NADT) shown lower rates recurrence among patients minimal residual disease after treatment. The molecular features that distinguish exceptional responders from poor are not known. To identify genomic and histologic associated treatment resistance at baseline. Targeted biopsies were obtained 37 men intermediate- to high-risk before...
The PI3K-AKT pathway has pleiotropic effects and its inhibition long been of interest in the management prostate cancer, where a compensatory increase PI3K signaling reported following androgen receptor (AR) blockade. Prostate cancer cells can also bypass AR blockade through induction other hormone receptors, particular glucocorticoid (GR). Here we demonstrate that AKT significantly decreases cell proliferation both cytostatic cytotoxic effects. effect is enhanced by most pronounced models...
Abstract Recent data show that extracellular signals are transmitted through a network of proteins rather than hierarchical signaling pathways, suggesting the inhibition single component canonical pathway is insufficient for treatment cancer. The biologic outcome inherently more robust and resistant to component. In this study, we conducted functional chemical genetic screen identify novel interactions between inhibitors would not be predicted on basis our current understanding networks. We...
Localized prostate cancer develops very slowly in most men, with the androgen receptor (AR) and MYC transcription factors amongst well-characterized drivers of tumorigenesis. Canonically, up-regulation luminal cells functions to oppose terminally differentiating effects AR. However, are pleiotropic inconsistent a poorly proliferative phenotype. Here we show that increased expression activity associated down-regulation MEIS1, HOX-family factor. Using RNA-seq profile series human specimens...
Antibody-drug conjugates(ADCs) are promising targeted cancer therapy; however, patient selection based solely on target antigen expression without consideration for cytotoxic payload vulnerabilities has plateaued clinical benefits. Biomarkers to capture patients who might benefit from specific ADCs have not been systematically determined any cancer. We present a comprehensive therapeutic and biomarker analysis of B7H3-ADC with pyrrolobenzodiazepine(PBD) in 26 treatment-resistant, metastatic...
The androgen receptor (AR) remains a pivotal target in castration-resistant prostate cancer (CRPC), as its continued activity presents therapeutic vulnerability. Reprogramming of the AR cistrome, shifting from canonical (typical or standard) to non-canonical (atypical non-standard) form, is associated with disease progression. While signatures are prevalent benign and localized cancer, advanced CRPC exhibits predominance elements. This cistrome linked enzalutamide resistance, standard...
// Devin G. Roller 1 , Brian Capaldo 2 Stefan Bekiranov Aaron J. Mackey 3 Mark R. Conaway Emanuel F. Petricoin 4 Daniel Gioeli Michael Weber Department of Microbiology, Immunology, and Cancer Biology, University Virginia, Charlottesville, VA, 22908 USA Biochemistry Molecular Genetics, Public Health Sciences, Center for Applied Proteomics Medicine, School Systems College Science, George Mason University, Manassas, VA 20110, Correspondence to: Weber, e-mail: mjw@virginia.edu Keywords:...
Metastatic prostate cancer is initially sensitive to androgen receptor inhibition, but eventually becomes castration-resistant (mCRPC). Early use of more intensive therapies targeting and other oncogenic drivers in treatment-naïve primary (PC) may be effective than that advanced mCRPC. However, analysis tumors not reveal targetable metastatic are subclonal the tumor or acquired at sites.PC samples spanning one patient's clinical course: diagnostic biopsies, pre- post-enzalutamide rapid...
Abstract To resist lineage-dependent therapies such as androgen receptor inhibition, prostate luminal epithelial adenocarcinoma cells often adopt a stem-like state resulting in lineage plasticity and phenotypic heterogeneity. Castrate-resistant can transition to neuroendocrine (NE) occasionally amphicrine, co-expressed NE, phenotypes. We developed castrate-resistant cancer (CRPC) patient-derived organoid models that preserve heterogeneity of the originating tumor, including an amphicrine...
Summary Background B cells play a critical role in the development and maintenance of food allergy by producing allergen‐specific IgE. Despite importance IgE‐mediated allergy, identity sIgE ‐producing human how IgE is regulated are poorly understood. Objective To identify immunophenotypes circulating associated with production galactose‐alpha‐1,3‐galactose‐specific patients red meat allergy. Methods PBMC samples obtained from 19 adults physician‐diagnosed 20 non‐meat allergic healthy...
Healthy bone marrow progenitors yield a co-ordinated balance of hematopoietic lineages. This shifts with aging toward enhanced granulopoiesis diminished erythropoiesis and lymphopoiesis, changes which likely contribute to the development disorders in elderly. In this study, RUNX3 was identified as stem progenitor cell factor whose levels decline humans mice. is exaggerated cells from subjects diagnosed unexplained anemia Hematopoietic elderly patients had erythroid but unaffected...
Abstract Aims In light of recent data regarding inflammatory signalling pathways in cardiovascular disease and the recently demonstrated impact pharmacologic inhibition interleukin-1β (IL-1β) heart failure, primary aim was to assess physiologic effects cardiac resynchronization therapy (CRT) on expression systemic inflammatory, immune-modulatory, metabolic, apoptotic genes peripheral blood mononuclear cells (PBMCs) patients with failure. Methods results We used RNA sequencing (RNA-Seq)...
Integrins α1β1 (CD49a), α2β1 (CD49b) and αEβ7 (CD103) mediate retention of lymphocytes in peripheral tissues, their expression is upregulated on tumor infiltrating (TIL) compared to circulating lymphocytes. Little known about what induces these integrins (RI) nor whether RI define subsets the microenvironment (TME) with a specific phenotype. Human metastatic melanoma-derived CD8 TIL could be grouped into five subpopulations based patterns: RIneg, CD49a+ only, CD49a+CD49b+, CD49a+CD103+, or...
Rationale The rationale was to utilize a bioinformatics approach identify miRNA binding sites in genes with single nucleotide mutations (SNPs) discover pathways heart failure (HF). Objective objective focus on the containing miRNAs that were significantly altered end-stage HF and response left ventricular assist device (LVAD). Methods Results BEDTools v2.14.3 used discriminate SNPs within predicted 3′UTR sites. A member of miR-15/107 family, miR-16, decreased circulation patients increased...
Abstract Nonbiased mutational screening to identify essential genes and pathways in cancer is a powerful approach for understanding underlying biology as well the identification of potential therapeutic targets. Epigenetic (EPI) transcriptional factors (TF) play an important role change phenotype lineage plasticity from adenocarcinoma castration resistant prostate (CRPC), double negative (DN) or treatment-induced neuroendocrine (NEPC). When RB1 loss occurs combination with TP53 alterations,...
Fifty percent of cutaneous melanomas are driven by activated BRAFV600E, but tumors treated with RAF inhibitors, even when they respond dramatically, rapidly adapt and develop resistance. Thus, there is a pressing need to identify the major mechanisms intrinsic adaptive resistance drug combinations that target these mechanisms. In combinatorial screen on panel 12 treatment-naïve BRAFV600E mutant melanoma cell lines varying levels mitogen-activated protein kinase (MAPK) pathway inhibition, we...
ABSTRACT Background In head and neck squamous cell carcinoma (HNSCC), resistance to single‐agent targeted therapy may be overcome by co‐targeting of compensatory signaling pathways. Methods A drug screen with 120 combinations was used on 9 HNSCC lines. Results Multiple novel demonstrated synergistic growth inhibition. Combining the insulin‐like factor‐1 receptor (IGF‐1R) inhibitor, BMS754807, either human epidermal factor (HER)‐family BMS599626, or Src‐family kinase dasatinib, resulted in...
Novel therapeutics for inflammatory bowel disease (IBD) are under development, yet mechanistic readouts at the tissue level lacking. Techniques to assess intestinal immune composition could represent a valuable tool mechanism of action (MOA) studies novel drugs. Mass cytometry enables analysis cell infiltrate and corresponding molecular fingerprints with unprecedented resolution. Here, we aimed optimize methodology isolation cryopreservation cells from allow potential implementation mass in...