A5076321493- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Circular RNAs in diseases
- Occupational and environmental lung diseases
- Cancer-related gene regulation
- RNA modifications and cancer
- MicroRNA in disease regulation
- Single-cell and spatial transcriptomics
- Genomics, phytochemicals, and oxidative stress
- CAR-T cell therapy research
- Pleural and Pulmonary Diseases
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Cancer-related molecular mechanisms research
- Immune Cell Function and Interaction
- Ferroptosis and cancer prognosis
- Chromatin Remodeling and Cancer
- Genomics and Chromatin Dynamics
- Acute Myeloid Leukemia Research
- Lung Cancer Research Studies
- Sarcoma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Neurofibromatosis and Schwannoma Cases
- Cancer Immunotherapy and Biomarkers
- Medical Imaging and Pathology Studies
The University of Texas MD Anderson Cancer Center
2019-2025
The University of Texas Health Science Center at Houston
2022
Center for Genomic Science
2022
Center for Translational Molecular Medicine
2022
Postgraduate School of Molecular Medicine
2013-2017
Medical University of Warsaw
2013-2017
Greater Poland Cancer Center
2013-2017
Ekaterinburg Research Institute of Viral Infections
2017
Poznan University of Medical Sciences
2015-2016
The epithelial-to-mesenchymal transition (EMT) plays a critical role during normal development and in cancer progression. EMT is induced by various signaling pathways, including TGF-β, BMP, Wnt-β-catenin, NOTCH, Shh, receptor tyrosine kinases. In this study, we performed single-cell RNA sequencing on MCF10A cells undergoing TGF-β1 stimulation. Our comprehensive analysis revealed that progress through at different paces. Using pseudotime clustering reconstruction of gene-expression profiles...
Abstract In contrast to the curative effect of allogenic stem cell transplantation in acute myeloid leukemia via T activity, only modest responses are achieved with checkpoint-blockade therapy, which might be explained by phenotypes and receptor (TCR) repertoires. Here, we show paired single-cell RNA analysis TCR repertoire profiling bone marrow cells relapsed/refractory patients pre/post azacytidine+nivolumab treatment that disease-related subsets highly heterogeneous, their abundance...
Abstract T-cell acute lymphoblastic leukemia (T-ALL) is commonly driven by activating mutations in NOTCH1 that facilitate glutamine oxidation. Here we identify oxidative phosphorylation (OxPhos) as a critical pathway for cell survival and demonstrate direct relationship between , elevated OxPhos gene expression, acquired chemoresistance pre-leukemic leukemic models. Disrupting with IACS-010759, an inhibitor of mitochondrial complex I, causes potent growth inhibition through induction...
Abstract Purpose: Cisplatin (CDDP)-based chemotherapy is a first-line treatment for patients with advanced head and neck squamous cell carcinomas (HNSCC), despite high rate of failures, acquired resistance, subsequent aggressive behavior. The purpose this study was to the mechanism CDDP resistance metastasis in HNSCC. We investigated role NRF2 pathway activation as driven event tumor progression Experimental Design: Human HNSCC lines that are highly resistant were generated. Clonogenic...
Reprogramming to induced pluripotent stem cells (iPSCs) and differentiation of (PSCs) are regulated by epigenetic machinery. Tripartite motif protein 28 (TRIM28), a universal mediator Krüppel-associated box domain zinc fingers (KRAB-ZNFs), is known regulate both processes; however, the exact mechanism identity participating KRAB-ZNF genes remain unknown. Here, using reporter system, we show that TRIM28/KRAB-ZNFs alter DNA methylation patterns in addition H3K9me3 cause stable gene repression...
// Patrycja Czerwińska 1, 2, 3 , Parantu K. Shah 4 Katarzyna Tomczak Marta Klimczak Sylwia Mazurek Barbara Sozańska 5 Przemysław Biecek 5, 6 Konstanty Korski 7 Violetta Filas Andrzej Mackiewicz 2 Jannik N. Andersen Maciej Wiznerowicz 1 Laboratory for Gene Therapy, Department of Diagnostics and Cancer Immunology, Greater Poland Centre, Poznan, Chair Medical Biotechnology, Poznan University Sciences, Postgraduate School Molecular Medicine, Warsaw, Institute Applied Science, Texas MD Anderson...
Enhancer aberrations are beginning to emerge as a key epigenetic feature of colorectal cancers (CRC), however, comprehensive knowledge chromatin state patterns in tumour progression, heterogeneity these and imparted therapeutic opportunities remain poorly described.We performed epigenomic characterisation by mapping 222 profiles from 69 samples (33 adenocarcinomas, 4 adenomas, 21 matched normal tissues 11 colon cancer cell lines) for six histone modification marks: H3K4me3 Pol II-bound...
Imaging-based spatial transcriptomics (ST) is evolving rapidly as a pivotal technology in studying the biology of tumors and their associated microenvironments. However, strengths commercially available ST platforms have not been systematically evaluated using rigorously controlled experiments. In this study, we used serial 5-µm sections formalin-fixed, paraffin-embedded surgically resected lung adenocarcinoma pleural mesothelioma tumor samples tissue microarrays to compare performance...
Abstract Background: Transforming growth factor-beta 1 (TGFβ1) plays a crucial role in tumor progression and immunosuppression cancer. SAR439459 is second-generation monoclonal antibody that targets all TGFβ isoforms. A first-in-human study (NCT03192345) established the dose at 15 mg/kg every three weeks as initial recommended phase 2 dose. Methods: TACTIC (NCT04729725) Ib dose-expansion trial to evaluate combination of (anti-TGF-β) cemiplimab (anti-PD1) pts with advanced solid tumors. Pts...
Novel therapeutic strategies targeting glioblastoma (GBM) often fail in the clinic, partly because preclinical models which hypotheses are being tested do not recapitulate human disease. To address this challenge, we took advantage of our previously developed spontaneous Qk/Trp53/Pten (QPP) triple-knockout model GBM, comparing immune microenvironment QPP mice with that patient-derived tumors to determine whether provides opportunity for gaining insights into tumor physiopathology and...
Abstract Acute myeloid leukemia (AML) is a heterogeneous disease characterized by high rate of therapy resistance. Since the cell origin can impact response to therapy, it crucial understand lineage composition AML cells at time Here we leverage single-cell chromatin accessibility profiling 22 bone marrow aspirates from eight patients resistance and following subsequent characterize their landscape. Our findings reveal complex architecture therapy-resistant that are primed for stem...
Abstract Purpose: Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TIL) historically yields a 40%–50% response rate in metastatic melanoma. However, the determinants outcome are largely unknown. Experimental Design: We investigated tumor-based genomic correlates overall survival (OS), progression-free (PFS), and to by interrogating tumor samples initially collected generate TIL infusion products. Results: Whole-exome sequencing (WES) data from 64 indicated positive correlation...
<h3>Background</h3> Single-cell spatial transcriptome (scST) technologies are evolving rapidly as potential tools that can help to unveil the tumor biology of cancer and allow investigation multiple targets, gene signaling pathways, cell-cell interactions crucial understanding microenvironment (TME). However, performance evaluation these platforms comparison with morphological biological data have not been performed previously. <h3>Methods</h3> We used formalin-fixed paraffin-embedded (FFPE)...
ABSTRACT Chromatin deregulation is an emerging hallmark of cancer. However, the extent epigenetic aberrations during tumorigenesis and their relationship with genetic are poorly understood. Using ChIP-sequencing for enhancers (H3K27ac H3K4me1), promoters (H3K4me3), active transcription (H3K79me2) polycomb (H3K27me3) or heterochromatin (H3K9me3) repression we generated chromatin state profiles in metastatic melanoma using 46 tumor samples cell lines. We identified a strong association NRAS,...
Abstract Acute myeloid leukemia (AML) and effector cells of immune checkpoint blockade (ICB) therapy co-reside in a complex bone marrow (BM) milieu. The interplay tumor intrinsic microenvironment (TME) mechanisms that influences the response to ICB-based therapies AML have not been elucidated. Here we report our analyses single cell RNA profiling more than 127,000 BM from healthy donors relapsed/refractory (R/R) patients at pre/post treatment with azacitidine/nivolumab, paired T receptor...
LAG3 is an inhibitory receptor expressed by T cells related to inhibition of IFNg production and mitochondrial biogenesis in naive CD4 cells. Combined expression with other immune checkpoints (ICs) like TIM3 PD1 associated exhausted It unknown if tumor-infiltrating lymphocytes (TIL) metabolism reprogramming the presence ICs impacting their anti-tumoral ability. TIL expansion was performed using 3.0 methodology from 62 surgically resected liposarcoma (LPS) tumors. Flow cytometry phenotypic...
Links between the tumor mutational signature, myeloid and tumor-infiltrating lymphocytes (TIL) phenotype functional states are lacking in malignant pleural mesothelioma (MPM). We performed multi-omic profiling of immune microenvironment (TIME) epithelioid MPM cases to provide insights that could drive novel therapeutic avenues future studies. tissue from patients who underwent surgical resection was confirmed by a pathologist as histological type. Flow cytometry, cytokine profiing TIL...
<h3>Background</h3> Pleural mesothelioma (PM) is an aggressive cancer linked to asbestos exposure. Our understanding of links between the tumor mutational signature, myeloid and tumor-infiltrating lymphocytes (TIL) phenotype functional states are lacking. To address this paucity knowledge, we performed multi-omic profiling immune microenvironment (TIME) PM cases provide insights that could drive novel therapeutic approaches for patients with surgically resectable tumors. <h3>Methods</h3>...