Background
The human microbiota, particularly the gut microbiome, plays a pivotal role in regulating host immune responses, metabolism, and signaling pathways. Microbial dysbiosis has been linked to cancer initiation and progression through mechanisms involving genotoxin production, chronic inflammation, and modulation of host cell signaling. Notably, certain microbes can influence tumor suppressor pathways, including the main tumor suppressor p53, altering cell cycle control, apoptosis, and genomic stability. Elucidating these molecular interactions is critical for advancing microbiome-targeted strategies in cancer prevention and therapy.
Models
To investigate microbiota-driven modulation of cancer pathways, we employ a multifaceted model system centered on Klebsiella pneumoniae, a gut bacteria associated with colorectal cancer. This includes in vitro co-culture systems to dissect cell responses, mouse and zebrafish models to study host–microbe interactions in vivo, and analysis of genomic and metagenomic data from patients to validate our findings. This integrative approach enables mechanistic insights into how K. pneumoniae and other pathobionts influence tumorigenesis, particularly through pathways such as p53.
Current projects in the lab
Inhibition of p53 tumor suppression by bacterial inflammation
p53 is the main tumor suppressor gene, inactivated by mutation in ~50% of tumors across all cancer types. In cancer retaining wild type p53, its tumor suppressive function is impaired by diverse mechanisms that are often not understood. We have shown that inflammation caused by K. pneumoniae and other Enterobacteriaceae robustly inhibits p53 functions (Oncogene, 2022). This project investigates the mechanisms of p53 inhibition by inflammation, its consequences for tumorigenesis and aims to reactivate p53 activity in inflammatory context for cancer therapy.
Impact of K. pneumoniae type VI secretion system on cancer
The Type VI Secretion System (T6SS) is a molecular weapon used by bacteria to secrete toxic effectors, shaping microbial communities and modulating host responses. We discovered an unexpected link between the activity of K. pneumoniae T6SS and colorectal cancer. By dissecting the role of K. pneumoniae T6SS in inflammation, immune modulation, and microbial competition within the gut microbiota, we aim to uncover the mechanisms by which T6SS contributes to tumorigenesis. Ultimately, the project seeks to investigate T6SS as a therapeutic target to mitigate bacteria-driven cancer-promoting processes.
Mechanisms of K. pneumoniae colibactin genotoxicity
Genotoxins are small bacterial molecules that cause DNA damage in the host cells, leading to cell transformation and cancer. K. pneumoniae encodes the colibactin, a genotoxin known to cause specific mutations in the colonic epithelium. This project investigates the molecular mechanisms of colibactin secretion and trafficking, as well as the consequences of colibactin-associated DNA damage for the host and the bacteria. We aim to identify novel bacterial or host targets for therapeutic intervention against genotoxins.
Role of p53 in immune response to infection and cancer
The tumor suppressor p53 is a master transcription factor that controls a broad range of target genes. While best known for its canonical roles in cell cycle arrest and apoptosis, the p53 pathway also regulates many non-canonical processes, including DNA repair, metabolism, autophagy, and immune response. This project investigates how p53 target genes regulates immune cells and how they influence the response to bacterial infections and cancer immunosurveillance. By exploring these molecular mechanisms, we aim to uncover new insights on the interplay between p53 and the immune response that could be exploited for immunotherapy.
Collaborative projects
Development of novel tools for deep secretome analysis
The secretome, i.e. the ensemble of proteins secreted by cells, plays a key role in intercellular communication, from tumor–microenvironment signaling to host–pathogen interactions. Comprehensive analysis of secreted proteins remains highly challenging due to their low abundance and dynamic range. In collaboration with Saei’s lab (Karolinska Institute) and Mahmoudi’s lab (Michigan State University), we are developing advanced, untargeted proteomics approaches based on mass spectrometry to enable deeper profiling of the secretome. Improving detection sensitivity and quantitative accuracy will open new exciting opportunities to characterize cell–cell communication across our different projects.
Integrative proteomics and AI-driven discovery of next-generation antibiotics
The rapid emergence of antibiotic resistance poses a major threat to global health. In this project, carried out in collaboration with Saei’s lab (Karolinska Institute) and Collins’s lab at the Broad Institute (MIT), we combine machine learning with advanced proteomics to develop novel antimicrobial compounds (Cell, 2025). Our targets are not only oncogenic pathogens such as Klebsiella pneumoniae and Helicobacter pylori, but also other clinically relevant bacteria (Escherichia coli, Staphylococcus aureus, Neisseria gonorrhoeae).