Research and development of new therapeutic methods in blood tumors

Main Activity 1: Genomic Profiling of Monoclonal Gammopathies – Identification of Molecular Targets

The goal of this activity is to expand diagnostic options for hematologic malignancies, specifically monoclonal gammopathies, using less invasive approaches, thereby broadening the diagnostic panel and stratification of patients with monoclonal gammopathies.

This activity will be carried out in phases with defined objectives, expected outputs, benefits, and insights:

• Identification of molecular changes in tumor cells of patients in resistant/aggressive stages of monoclonal gammopathies
  • DNA and RNA sequencing from samples of tumor and healthy tissue
  • Identification of changes at various levels (mutations, gene expression) and comparison with less aggressive stages
  • Integration of data from different levels of genomic regulation
  • Bioinformatic evaluation
    
    
• Identification of molecular biomarkers using minimally invasive techniques – liquid biopsies (peripheral blood)
  • Circulating cells, cell-free DNA, correlation with disease aggressiveness
  • Bioinformatic evaluation
    
    
• Design of a diagnostic panel for the diagnosis and stratification of patients with monoclonal gammopathies
  • Circulating cells, cell-free DNA, correlation with disease aggressiveness
  • Bioinformatic evaluation
    
    
• Study of epigenetic changes in monoclonal gammopathies
  • Study of methylation profiles
  • Analysis of histone acetylation and non-histone protein changes
  • Chromatin remodeling studies
  • Flow cytometry, single-cell analysis (gene expression), proteomics
  • Data integration
    
    
• Study of tumor microenvironment interactions in monoclonal gammopathies
• Publication activities and intellectual property protection
  
  

Main Activity 2: Study of Molecular Basis of Hematologic Malignancies to Identify Diagnostic, Predictive, and Stratification Biomarkers and Novel Therapeutic Targets for Precision Medicine

The goal of this activity is to enhance diagnostic capabilities for hematologic malignancies such as multiple myeloma, acute myeloid leukemia, and lymphomas, focusing on oncogenic cellular signaling to identify new therapeutic targets.

Activity steps with specific objectives, expected outputs, and insights include:

• Validation and functional characterization of mutations and genes in hematologic malignancies
  • Literature review and bioinformatic exploration of genomic databases
  • Selection of candidate genes and mutations
  • Preparation of genetic model systems
  • Development and optimization of phenotypic screening methods
  • Functional testing of positive hits
    
    
• Oncogenic cellular signaling for identifying new therapeutic targets
  • Introduction and optimization of cell signaling analysis methods
  • Therapeutic modulation of signaling
  • Selection of candidate processes and therapeutic targets
  • Collaboration with commercial partners for the design and development of inhibitors
    
    
• Study of the biology of multiple myeloma and minimal residual disease (MRD) in the bone marrow microenvironment
  • Preparation of cell models, organoids, and in vivo (mouse) models
  • Testing and analysis of organoids and in vivo models
    
    
• Accreditation of a new doctoral study program titled Biomedicine (taught in English)
  
  
• Publication, intellectual property protection, spin-off creation, and grant preparation
  
  

Main Activity 3: Cell Therapy

The goal is to develop suitable technological procedures for cell and immunotherapy, focusing specifically on CAR T lymphocytes and Natural Killer cells.

Activity steps include:

• Technological procedure for universal CAR T lymphocyte production
  • Identification and testing of cell types
  • Implementation of genetic manipulations
  • Optimization of cultivation conditions
  • Preclinical testing
    
    
• Technological procedure for modified Natural Killer (NK) cell production
• Identification and testing of cell types
• Implementation of genetic manipulations
• Optimization of cultivation conditions
• Preclinical testing
  
  
• Development of innovative methods for improving immunotherapy
  • Development of tools for CAR receptor modulation
  • Design and testing of new CAR receptors
  • Collaboration with commercial entities
    
    
• Optimization and validation of new immunotherapy-based approaches
  • Validation and implementation of biomarkers for immunotherapy
  • Testing new therapeutic targets for immunotherapy
    
    
• Collaboration and technology transfer activities
  
  

Collaboration with Other Teams

Due to the highly interdisciplinary nature of the research, VP6 collaborates on specific activities with the following teams:

• VP1: Joint preparation of a diagnostic panel for hematologic malignancies and the Biomedicine doctoral program.
• VP2: Shared infrastructure for detecting oxidative damage in biological membranes and macromolecules during analytic research phases.
• VP3: Testing molecular interaction sites and validating model structures in vitro and in vivo.

Additionally, during experimental research, at least two rehabilitation-focused collaborators will contribute to developing bioinformatics software and cell therapies without generating profit.