A5010633283- Autophagy in Disease and Therapy
- Acute Myeloid Leukemia Research
- Retinoids in leukemia and cellular processes
- Ubiquitin and proteasome pathways
- Pancreatic function and diabetes
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Hematopoietic Stem Cell Transplantation
- RNA modifications and cancer
- Cancer-related gene regulation
- Cancer, Lipids, and Metabolism
- Chronic Myeloid Leukemia Treatments
- Kruppel-like factors research
- Cancer-related Molecular Pathways
- Mesenchymal stem cell research
- Metabolism, Diabetes, and Cancer
- Histone Deacetylase Inhibitors Research
- Platelet Disorders and Treatments
- Single-cell and spatial transcriptomics
- Cell death mechanisms and regulation
- Microfluidic and Bio-sensing Technologies
- Endoplasmic Reticulum Stress and Disease
- Erythrocyte Function and Pathophysiology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Acute Lymphoblastic Leukemia research
University of Lausanne
2023-2025
University of Bern
2013-2024
Action Network
2020-2022
Institute for Research in Immunology and Cancer
2013-2016
Université de Montréal
2014-2016
Abstract The family of hexokinases (HKs) catalyzes the first step glycolysis, ATP-dependent phosphorylation glucose to glucose-6-phosphate. While HK1 and HK2 are ubiquitously expressed, less well-studied HK3 is primarily expressed in hematopoietic cells tissues highly upregulated during terminal differentiation some acute myeloid leukemia (AML) cell line models. Here we show that expression predominantly originating from upregulation this glycolytic enzyme not restricted leukemic but also...
Autophagy is an intracellular degradation system that ensures a dynamic recycling of variety building blocks required for self-renewal, homeostasis, and cell survival under stress. We used primary acute myeloid leukemia (AML) samples human AML lines to investigate the regulatory mechanisms autophagy its role in differentiation. found significantly lower expression key autophagy- (ATG-) related genes as compared healthy granulocytes, increased autophagic activity during all-trans retinoic...
Abstract Fatty acid synthase (FASN) is the only human lipogenic enzyme available for de novo fatty synthesis and often highly expressed in cancer cells. We found that FASN mRNA levels were significantly higher acute myeloid leukemia (AML) patients than healthy granulocytes or CD34 + hematopoietic progenitors. Accordingly, decreased during all- trans retinoic (ATRA)-mediated granulocytic differentiation of promyelocytic (APL) cells, partially via autophagic degradation. Furthermore, our data...
Diffuse large B-cell lymphomas (DLBCL) represent approximately 30% of all non-Hodgkin [1].The recognised cell-oforigin (COO) has classified two major DLBCL subtypes: Germinal (GCB) and Activated (ABC) lymphomas.Between 20-50% patients experience relapse refractory disease following first-line therapy R-CHOP [2].The molecular heterogeneity contributes to varied clinical outcomes chemotherapy targeted agents including ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor [2, 3].Ibrutinib...
The basic leucine zipper transcription factor CCAAT/enhancer binding protein alpha (CEBPA) codes for a critical regulator during neutrophil differentiation. Aberrant expression or function of this contributes to the development acute myeloid leukemia (AML). In study, we identified two novel unrelated CEBPA target genes, glycolytic enzyme hexokinase 3 (HK3) and krüppel-like 5 (KLF5) factor, by comparing gene profiles in cohorts wild-type mutant AML patients. addition, found CEBPA-dependent...
Significance Understanding how cell cycle and differentiation are coordinated during normal hematopoiesis will reveal molecular insights in leukemogenesis. LIM-only 2 (LMO2) is a transcriptional regulator that controls the erythroid lineage via activation of an erythroid-specific gene expression program. Here, we uncover unexpected function for LMO2 controlling DNA replication protein–protein interactions with essential enzymes. To our knowledge, this work provides first evidence...
LAMP2A and HSC70 are crucial players in chaperone-mediated autophagy (CMA), a targeted, lysosome-dependent protein degradation pathway. Elevated levels, indicative of increased CMA activity, observed several malignancies, downregulation may be exploited therapeutically. We evaluated the impact pulmonary squamous cell carcinomas (pSQCC). Antibodies were validated by knockdown overexpression experiments using three different lines. Expression levels tissue analyzed immunohistochemistry cohort...
In acute promyelocytic leukemia, granulocytic differentiation is arrested at the promyelocyte stage. The variant t(11;17) translocation produces two fusion proteins, leukemia zinc finger-retinoic acid receptor α (PLZF-RARα) and RARα-PLZF, both of which participate in development. Here we provide evidence that activity CCAAT/enhancer binding protein (C/EBPα), a master regulator differentiation, severely impaired leukemic promyelocytes with compared those associated t(15;17) translocation. We...
ABSTRACT DAPK2 is a proapoptotic protein that mostly expressed in the hematopoietic tissue. A detailed expression analysis two large AML patient cohorts revealed particularly low mRNA levels APL. were restored APL patients undergoing ATRA therapy. PML-RARA predominant lesion causing transcriptional repression of genes important for neutrophil differentiation. We found binding and PU.1, myeloid master regulator, to RARA PU.1 sites promoter. Ectopic non-APL, as well knocking down cells,...
Paclitaxel is a powerful chemotherapeutic drug, used for the treatment of many cancer types, including esophageal adenocarcinomas (EAC). Autophagy lysosome-dependent degradation process maintaining cellular homeostasis. Defective autophagy has been implicated in biology and therapy resistance. We aimed to assess impact on chemotherapy response EAC, with special focus paclitaxel. Responsiveness EAC cell lines, OE19, FLO-1, OE33 SK-GT-4, paclitaxel was assessed using Alamar Blue assays....
We have previously demonstrated that the death-associated protein kinase 2 (DAPK2) expression is significantly reduced in acute myeloid leukemia (AML), particularly promyelocytic (APL) blast cells. In this study, we aimed at further understanding DAPK2 function and regulation during arsenic trioxide (ATO) cytotoxic or all-trans retinoic acid (ATRA) differentiation therapy APL found p53 family member transactivation domain-p73 isoform (TAp73) binds to activates promoter, whereas...
Autophagy is a highly conserved degradation mechanism that essential for maintaining cellular homeostasis. In human disease, autophagy pathways are frequently deregulated and there immense interest in targeting therapeutic approaches. Accordingly, need to determine autophagic activity tissues, an endeavor hampered by the fact characterized flux of substrates whereas histology informs only about amounts localization regulators at single timepoint. Despite this challenging task, considerable...
Colorectal cancer, along with its high potential for recurrence and metastasis, is a major health burden. Uncovering proteins pathways required tumor cell growth necessary the development of novel targeted therapies. Ajuba member LIM domain family whose expression positively associated numerous cancers. Our data shows that highly expressed in human colon cancer tissue lines. Publicly available from The Cancer Genome Atlas negative correlation between survival patients cancer. To investigate...
Acute myeloid leukemia (AML) is a cancer of the hematopoietic system characterized by hyperproliferation undifferentiated cells lineage. While most AML therapies are focused toward tumor debulking, all-trans retinoic acid (ATRA) induces neutrophil differentiation in subtype acute promyelocytic (APL). Macroautophagy has been extensively investigated context various cancers and often dysregulated where it can have context-dependent pro- or anti-leukemogenic effects. On contrary, implications...
Chaperone Mediated Autophagy (CMA) is a selective autophagy pathway deregulated in many cancers. In this study, we were aiming at understanding the importance of CMA breast cancer. To end, examined expression markers HSP8 and LAMP2A different cancer cell lines found wide range levels across analyzed. Next, applied specific immunohistochemical staining protocol to tissue microarray derived from cohort 365 patients. Therefore, able find correlation high but not HSPA8 (HSC70) with worse disease...