A5024296376- Multiple Myeloma Research and Treatments
- CAR-T cell therapy research
- Autophagy in Disease and Therapy
- Cancer-related molecular mechanisms research
- Immune Cell Function and Interaction
- Pharmacological Receptor Mechanisms and Effects
- Protein Degradation and Inhibitors
- Phagocytosis and Immune Regulation
- CRISPR and Genetic Engineering
- interferon and immune responses
- Histone Deacetylase Inhibitors Research
- Cancer, Stress, Anesthesia, and Immune Response
- Lymphoma Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Ferroptosis and cancer prognosis
- Cancer Genomics and Diagnostics
- Cytokine Signaling Pathways and Interactions
- PARP inhibition in cancer therapy
- Synthesis and Biological Evaluation
- Calcium signaling and nucleotide metabolism
- Cancer, Hypoxia, and Metabolism
- Synthesis and Characterization of Heterocyclic Compounds
- Adenosine and Purinergic Signaling
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
Candiolo Cancer Institute
2023-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2024
University of Ostrava
2020-2024
University Hospital Ostrava
2022-2024
Dana-Farber Cancer Institute
2022
Immunogenic cell death (ICD) is a form of by which cancer treatments can induce clinically relevant antitumor immune response in broad range cancers. In multiple myeloma (MM), the proteasome inhibitor bortezomib an ICD inducer and creates durable therapeutic responses patients. However, eventual relapse resistance to appear inevitable. Here, integrating patient transcriptomic data with analysis calreticulin (CRT) protein interactors, we found that GABA type A receptor-associated (GABARAP)...
During innate immune responses, myeloid differentiation primary response 88 (MyD88) functions as a critical signaling adaptor protein integrating stimuli from toll-like receptors (TLR) and the interleukin-1 receptor (IL-1R) family translates them into specific cellular outcomes. In B cells, somatic mutations in MyD88 trigger oncogenic NF-κB independent of stimulation, which leads to development B-cell malignancies. However, exact molecular mechanisms downstream targets remain unresolved. We...
In multiple myeloma (MM), tumor cells reprogram metabolic pathways to sustain growth and monoclonal immunoglobulin production. This study examines acetyl-CoA carboxylase 1 (ACC1), the enzyme driving rate-limiting step in de novo lipogenesis (DNL), MM reprogramming, particularly c-MYC (MYC)-driven subtypes. ACC1 expression was evaluated across genetic subgroups, focusing on MYC translocations. Functional studies using inhibitors knockdown assessed cell growth, lipid synthesis, homeostasis...
Abstract Serum monoclonal immunoglobulin (Ig) is the main diagnostic factor for patients with multiple myeloma (MM), however its prognostic potential remains unclear. On a large MM patient cohort (n = 4146), we observe no correlation between serum Ig levels and survival, while amount of intracellular has strong predictive effect. Focused CRISPR screen, transcriptional proteomic analysis identify deubiquitinase OTUD1 as critical mediator synthesis, proteasome inhibitor sensitivity tumor...
Abstract In multiple myeloma (MM), the proteasome inhibitor bortezomib (BTZ) triggers immunogenic cell death (ICD), a critical mechanism by which drug stimulates an anti-MM immune response. During ICD, dying cancer releases danger signals like calreticulin (CRT), attract dendritic cells (DCs) to engulf and present its antigens T cells. Cancer may employ several strategies restrain outcome, including interfering with exposure of CRT on surface. Such resistance mechanisms hinder activation...
Abstract Long noncoding RNAs (lncRNAs) constitute a significant portion of the human transcriptome, yet their precise role in tumor cells remains elusive. In our study focusing on multiple myeloma (MM), we employed CRISPR-Cas13d endonuclease's RNA-targeting capabilities to establish an innovative functional transcriptomics screening platform. This platform facilitated comprehensive identification tumor-promoting lncRNAs (tp-lncRNAs) MM and provided mechanistic insights. Utilizing RNA-seq...
The adaptive immune response critically hinges on the functionality of T cell receptors, governed by complex molecular mechanisms, including ubiquitination. In this study, we delved into role in immunity, focusing cell-B conjugate formation and activation. Using a CRISPR-Cas9 screening approach targeting deubiquitinases genes Jurkat cells, identified BAP1 as key positive regulator formation. Subsequent investigations knockout cells revealed impaired activation, evidenced decreased MAPK NF-kB...
Malignant melanoma is an aggressive cancer, with a high risk of metastasis and mortality rates, characterized by cancer cell heterogeneity complex tumor microenvironment (TME). Single biology ideal powerful tool to address these features at molecular level. However, this approach requires enzymatic dissociation that can influence cellular coverage. By contrast, single nucleus RNA sequencing (snRNA-seq) has substantial advantages including compatibility frozen samples the elimination...
Topic: 20. Lymphoma Biology & Translational Research Background: Myeloid differentiation primary response 88 (MyD88) serves as a crucial signaling adaptor protein during innate immune responses, integrating stimuli from the Toll-like receptors (TLR) and Interleukin-1 receptor (IL-1R) family translating them into specific cellular outcomes. In B cells, somatic mutations of MyD88 induce oncogenic NF-κB independently stimulation, resulting in onset B-cell malignancies. However, precise...