A5017367163- Ovarian cancer diagnosis and treatment
- Microtubule and mitosis dynamics
- Cancer-related molecular mechanisms research
- Cancer, Lipids, and Metabolism
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- RNA modifications and cancer
- Cancer Mechanisms and Therapy
- Renal and related cancers
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Single-cell and spatial transcriptomics
- Tissue Engineering and Regenerative Medicine
- Reproductive Biology and Fertility
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Ubiquitin and proteasome pathways
- Microscopic Colitis
- Microencapsulation and Drying Processes
- Advancements in Transdermal Drug Delivery
- Glycosylation and Glycoproteins Research
- Prenatal Screening and Diagnostics
- Tryptophan and brain disorders
- Cancer, Hypoxia, and Metabolism
- Immunotherapy and Immune Responses
K.N.Toosi University of Technology
2025
Pennsylvania State University
2024
University of Oxford
2016-2023
MRC Weatherall Institute of Molecular Medicine
2018-2023
John Radcliffe Hospital
2018-2022
Medical Research Council
2021
Purpose: Salt-inducible kinase 2 (SIK2) is a centrosome required for mitotic spindle formation and potential target ovarian cancer therapy. Here, we examine the effects of novel small-molecule SIK2 inhibitor, ARN-3236, on sensitivity to paclitaxel in cancer.Experimental Design: expression was determined tissue samples cell lines. ARN-3236 tested its efficiency inhibit growth enhance cultures xenografts siRNA were compared their ability produce nuclear-centrosome dissociation, splitting,...
Abstract Though used widely in cancer therapy, paclitaxel only elicits a response fraction of patients. A strong determinant tumor is the state microtubule dynamic instability. However, whether manipulation this physiological process can be controlled to enhance has not been tested. Here, we show previously unrecognized role microtubule-associated protein CRMP2 inducing bundling through its carboxy terminus. This activity significantly decreased when FER tyrosine kinase phosphorylates at...
Similar to tumor-initiating cells (TICs), minimal residual disease (MRD) is capable of reinitiating tumors and causing recurrence. However, the molecular characteristics solid tumor MRD drivers their survival have remained elusive. Here we performed dense multiregion transcriptomics analysis paired biopsies from 17 ovarian cancer patients before after chemotherapy. We reveal that while share important signatures with TICs, they are also characterized by an adipocyte-like gene expression...
The study of fallopian tube (FT) function in health and disease has been hampered by limited knowledge FT stem cells lack vitro models cell renewal differentiation. Using optimized organoid culture conditions to address these limitations, we find that is highly dependent on WNT/β-catenin signaling engineer endogenous reporter organoids biomark, isolate, characterize cells. functional approaches, as well bulk single-cell transcriptomics analyses, show an hormonally regulated WNT7A-FZD5 axis...
Abstract Purpose: Using RNA sequencing, we recently developed the 52-gene–based Oxford classifier of carcinoma ovary (Oxford Classic, OxC) for molecular stratification serous ovarian cancers (SOCs) based on profiles their cell origin in fallopian tube epithelium. Here, a 52-gene NanoString panel OxC to test robustness classifier. Experimental Design: We measured expression 52 genes an independent cohort prospectively collected SOC samples (n = 150) from homogenous who were treated with...
Summary The inter-differentiation between cell states promotes cancer survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that can be accurately measured when informed the molecular signatures normal cells origin. We surveyed transcriptomes ∼ 4000 fallopian tube epithelial (FTE) cells, origin serous ovarian (SOC), identified six FTE subtypes. used...
Abstract Background Inflammatory bowel disease is characterized by disturbed metabolism, including disrupted tryptophan (TRP) metabolism along the kynurenine pathway (KP). However, molecular mechanism how this fuels inflammation not understood. Here, we unravel rewiring of TRP in IBD combining murine DSS colitis with multi-omics longitudinal cohorts. Methods Serum metabolites were associated CRP, e/pMayo, SESCD and CDAI (n=83 UC, n=51 CD). Mucosal IDO1 QPRT expression (both KP enzymes;...
<p>Supplementary Figure 1 related to 2. (A) In vitro kinetic curve of SIK2 kinase activity in the presence ARN-3236. The reaction mixture contained recombinant protein (15 nM), ATP (10 μM), and substrate peptide (TORC2 aa162-179) (1 μM). (B-J) Indicated cells were treated same as 1B, Cell viability was tested Supplementary 2 3. (A-H) Different cell lines plated at density 8000/well 96-well plate, then sequentially with ARN-3236 (IC30 each line) or DMSO for 24 hr increasing...
<p>Supplementary Figures and Tables</p>
<p>Table S2. The QuPath classification results for the immunohistochemistry of CAPS in SOC tissue microarrays.</p>
<p>Supplementary Figure 1 related to 2. (A) In vitro kinetic curve of SIK2 kinase activity in the presence ARN-3236. The reaction mixture contained recombinant protein (15 nM), ATP (10 μM), and substrate peptide (TORC2 aa162-179) (1 μM). (B-J) Indicated cells were treated same as 1B, Cell viability was tested Supplementary 2 3. (A-H) Different cell lines plated at density 8000/well 96-well plate, then sequentially with ARN-3236 (IC30 each line) or DMSO for 24 hr increasing...
<p>Supplementary Figures and Tables</p>
<p>Table S2. The QuPath classification results for the immunohistochemistry of CAPS in SOC tissue microarrays.</p>
<div>Abstract<p><b>Purpose:</b> Salt-inducible kinase 2 (SIK2) is a centrosome required for mitotic spindle formation and potential target ovarian cancer therapy. Here, we examine the effects of novel small-molecule SIK2 inhibitor, ARN-3236, on sensitivity to paclitaxel in cancer.</p><p><b>Experimental Design:</b> expression was determined tissue samples cell lines. ARN-3236 tested its efficiency inhibit growth enhance cultures xenografts siRNA...
<div>AbstractPurpose:<p>Using RNA sequencing, we recently developed the 52-gene–based Oxford classifier of carcinoma ovary (Oxford Classic, OxC) for molecular stratification serous ovarian cancers (SOCs) based on profiles their cell origin in fallopian tube epithelium. Here, a 52-gene NanoString panel OxC to test robustness classifier.</p>Experimental Design:<p>We measured expression 52 genes an independent cohort prospectively collected SOC samples...
<div>Abstract<p><b>Purpose:</b> Salt-inducible kinase 2 (SIK2) is a centrosome required for mitotic spindle formation and potential target ovarian cancer therapy. Here, we examine the effects of novel small-molecule SIK2 inhibitor, ARN-3236, on sensitivity to paclitaxel in cancer.</p><p><b>Experimental Design:</b> expression was determined tissue samples cell lines. ARN-3236 tested its efficiency inhibit growth enhance cultures xenografts siRNA...