Glucocorticoids (GCs) are steroid hormones produced from cholesterol under the control of
the hypothalamic–pituitary–adrenal axis. They play essential roles in metabolism, immune
regulation, and stress adaptation, and synthetic analogs are widely used therapeutically. While
the classical genomic actions of GCs are mediated by the glucocorticoid receptor (GR) acting
as a transcription factor, increasing evidence indicates that GCs can also trigger rapid, non-
genomic effects independent o...
NUMB is a multifunctional adaptor protein historically recognized for its role in determining cell fate decisions through inhibition of NOTCH signaling, a process achieved via endocytic trafficking. Subsequently, NUMB has emerged as a significant tumor suppressor, particularly in the context of breast cancer, where it stabilizes the critical tumor suppressor protein p53 by inhibiting its targeting to proteasomal degradation by the E3 ubiquitin ligase MDM2. This role of NUMB is isoform-specifi...
Suicide is one of the leading causes of death worldwide, with over 700,000 deaths each year. In recent years, numerous studies have focused on analyzing its epidemiology and predisposing factors. Among the biological factors involved, cerebral glial cells have attracted growing attention due to postmortem evidence linking their pathological alterations to major depressive disorder (MDD) and suicidal behavior. The research project underlying this thesis focused on the postmortem analysis of hu...
Cellular quiescence is a reversible and actively maintained state that enables diverse cell types—including adult stem cells, hepatocytes, and T lymphocytes—to transiently suspend proliferation while preserving the ability to rapidly re-enter the cell cycle upon stimulation. In T lymphocytes, the controlled transition from quiescence to activation is essential for effective immune responses, whereas dysregulated re-entry into a quiescent-like state contributes to dysfunction and exhaustion in...
Histone Post-Translational Modifications (PTMs) are key epigenetic players in physiology and disease, generating a complex combinatorial code that regulates gene expression, nuclear functions and chromatin organization. Aberrant levels of histone PTMs are recognized as general hallmarks of cancer and their profiling in tumour can both allow the identification of epigenetic markers for patient stratification and suggest novel epigenetic pathways to be targeted for therapy.
With the aim to inv...
Mitochondria are key regulators of energy metabolism, apoptosis, and redox signaling, and their genome (mtDNA) is particularly vulnerable to genomic alterations due to its proximity to the respiratory chain, lack of protective histones, and limited repair capacity. Although mtDNA mutations have been implicated in carcinogenesis, their contribution to hematologic malignancies remains insufficiently understood, particularly with respect to low-level heteroplasmic variants.
In this study, we ...
The human gut microbiome, a complex community of microorganisms inhabiting the human gastrointestinal tract, is recognized as a critical modulator of host physiology. Imbalances in its composition have been linked with a range of human diseases, including cardiometabolic disorders. Diet is both a well-established determinant of cardiometabolic health and a major factor shaping the gut microbiome, yet many aspects of the diet–microbiome–health axis remain poorly understood, particularly regard...
Cancer cell genomes display numerous mutation patterns that subvert genome stability. DNA repair and damage response mechanisms are responsible for maintaining stability in normal cells. One such repair mechanism involves homologous recombination (HR) proteins BRCA2 which protects DNA replication intermediates from nuclease-mediated degradation. Emerging evidence demonstrates that HR proteins like BRCA2 co-evolved with the cytosine methylation machinery, suggesting a functional link between t...
Polycomb group (PcG) proteins are central regulators of cell identity, maintaining
transcriptional repression at CpG island-containing promoters through Polycomb Re-
pressive Complexes 1 and 2 (PRC1 and PRC2), which deposit H2AK119Ub1 and
H3K27me3, respectively. While the role of PcG proteins in embryonic stem cells (ESCs)
has been extensively studied, their mechanisms in di!erentiated tissues remain poorly
understood. This is crucial given PcG proteins are frequently mutated in cancer a...
Understanding tumor heterogeneity is essential for improving diagnosis, treatment, and drug development in oncology. This thesis explores how cutting-edge transcriptomic technologies and new computational frameworks can be used to dissect, interpret, and model the cellular complexity of solid tumors, with a particular focus on two case studies namely high-grade serous ovarian cancer (HGSC) and glioblastoma multiforme (GBM).
The first part of the thesis focuses on building and leveraging a ...