A5039929722- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Platelet Disorders and Treatments
- Acute Lymphoblastic Leukemia research
- Cancer-related Molecular Pathways
- CAR-T cell therapy research
- Digital Imaging for Blood Diseases
- Protein Degradation and Inhibitors
- Hemoglobinopathies and Related Disorders
- Hearing Loss and Rehabilitation
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- PI3K/AKT/mTOR signaling in cancer
- Vestibular and auditory disorders
- Hearing, Cochlea, Tinnitus, Genetics
- Immunodeficiency and Autoimmune Disorders
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Erythropoietin and Anemia Treatment
- Blood transfusion and management
- Protein Tyrosine Phosphatases
- Mechanisms of cancer metastasis
- Cell Image Analysis Techniques
- Peptidase Inhibition and Analysis
Novartis (Switzerland)
2016-2023
Novartis Institutes for BioMedical Research
2021-2023
59th Medical Wing
2019-2023
711th Human Performance Wing
2019-2023
Friedrich Miescher Institute
2014-2021
Novartis Foundation
2020
Translational Genomics Research Institute
2010
University of Otago
2010
The PI3K pathway is hyperactivated in many cancers, including 70 % of breast cancers. Pan- and isoform-specific inhibitors the are currently being evaluated clinical trials. However, responses to when used as single agents not efficient expected. In order anticipate potential molecular mechanisms resistance p110α isoform-selective inhibitor BYL719, we developed resistant cancer cell lines, assessed concomitant changes cellular signaling pathways using unbiased phosphotyrosine proteomics...
Abstract The immunologic microenvironment in various solid tumors is aberrant and correlates with clinical survival. Here, we present a comprehensive analysis of the immune environment acute myeloid leukemia (AML) bone marrow (BM) at diagnosis. We compared landscape formalin-fixed paraffin-embedded BM trephine samples from AML (n = 69), chronic (CML; n 56), B-cell lymphoblastic (B-ALL) patients 52) diagnosis to controls 12) 30 immunophenotype markers using multiplex immunohistochemistry...
In myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN), bone marrow (BM) histopathology is assessed to identify dysplastic cellular morphology, cellularity, blast excess. Yet, other morphologic findings may elude the human eye. We used convolutional neural networks extract features from 236 MDS, 87 MDS/MPN, 11 control BM biopsies. These predicted genetic cytogenetic aberrations, prognosis, age, gender in multivariate regression models. Highest prediction accuracy was found...
Eltrombopag stimulates multilineage hematopoiesis through intracellular iron chelation.
A genome-wide PiggyBac transposon-mediated screen and a resistance in PIK3CAH1047R-mutated murine tumor model reveal NF1 loss mammary tumors resistant to the phosphatidylinositol 3-kinase α (PI3Kα)-selective inhibitor alpelisib. Depletion of PIK3CAH1047R breast cancer cell lines patient-derived organoid shows that reduces sensitivity PI3Kα inhibition correlates with enhanced glycolysis lower levels reactive oxygen species (ROS). Unexpectedly, antioxidant N-acetylcysteine (NAC) sensitizes...
Purpose In the past decade, resting-state functional connectivity, acquired using magnetic resonance imaging (fMRI), has emerged as a popular measure of tinnitus, especially related to self-reported handicap or psychological reaction. The goal this study was assess replicability neural correlates namely, in same individuals over 2 sessions. Method Data were collected at different sites (University Illinois Urbana–Champaign and Joint Base San Antonio Wilford Hall Ambulatory Surgical Center)...
Resting state functional connectivity (RS-FC) studies of tinnitus over the years have produced inconsistent results. While findings can be organized into broad categories, such as increased correlations between auditory and limbic areas in patients a disrupted default mode network, there has been little one-to-one correspondence results across RS-FC tinnitus. some this variation explained by heterogeneity population, including severity, sources variability are unclear. To directly assess...
Thrombocytopenia, prevalent in the majority of patients with myeloid malignancies, such as myelodysplastic syndrome (MDS) or acute leukemia (AML), is an independent adverse prognostic factor. Azacitidine (AZA), a mainstay therapeutic agent for stem cell transplant–ineligible MDS/AML, often transiently induces further aggravates disease-associated thrombocytopenia by unknown mechanism. Here, we uncover critical role type-I interferon (IFN-I) signaling activation suppressing megakaryopoiesis...
is a figure showing that p110β activation does not correlate with loss of PTEN. Immunoblots lysates from parental and resistant cells treated for 24 hours as indicated. BYL719 (IC90) AEW541 (1 μM). (PDF 140 kb)
is a figure showing that combination of BYL719/AEW541 triggers apoptosis in BYL719-resistant cell lines. A Anti-cleaved PARP (T47D) or anti-PARP (MCF7) immunoblots lysates from parental and resistant cells treated for 24 hours as indicated. BYL719 (IC90), AEW541 (1 μM). B Parental were with (2 μM T47D 5 μM MCF7), (1 μM), the 72 hours. Percentage apoptotic (Annexin V-positive PI-negative) necrotic V PI-positive) are (PDF 158 kb)
Abstract Eltrombopag has been previously shown to be effective in reversing azacitidine‐mediated thrombocytopenia. This was further investigated the SUPPORT trial, a phase III study assessing efficacy/safety of eltrombopag plus azacitidine patients with intermediate‐ high‐risk myelodysplastic syndromes and The results did not support clinical benefit for addition azacitidine. We if somatic mutational profiles patient cohort were associated treatment outcomes. Based on available data, we...
Abstract The molecular events associated with the multi-step process of cell invasion and metastasis are poorly understood. Tumor necrosis factor receptor family member fibroblast growth factor-inducible 14 (Fn14) its ligand TWEAK (tumor factor-like weak inducer apoptosis) have recently emerged as a pro-invasive signaling mechanism indicator poor prognosis in breast cancer. Our laboratory has reported enhanced Fn14 expression significant proportion tumor samples, but not normal epithelium....