My research program aims to dissect the complex dynamics of host–environment interactions that sustain intestinal homeostasis, and to understand how disruptions in these interactions contribute to inflammatory bowel diseases (IBD) and colorectal cancer (CRC). I have built my scientific trajectory around studying how nuclear receptors shape the immune system, intestinal mucosal immunology, and tissue healing, using zebrafish and murine models alongside human primary cells.
We have also applied spatial transcriptomics to uncover gene programs and cellular features associated with mucosal healing, inflammation, and colorectal cancer. Using unique IBD and CRC patient cohorts, together with complementary animal models, we are now integrating multiple omic layers, including spatial transcriptomics, spatial proteomics, spatial metabolomics, and spatial metatranscriptomics, to gain a multidimensional understanding of intestinal biology in health and disease.
Our lab combines expertise in clinical and experimental research, the development of animal models and organoid systems, and advanced computational biology. Ultimately, my goal is to identify metabolites and pathways that can be therapeutically targeted to restore intestinal homeostasis following disease.
We currently have several ongoing projects in the lab:
- Genetic and Environmental Crosstalk in Intestinal Homeostasis
Functional annotation of IBD-associated noncoding variants remains challenging due to their low penetrance, which often results in subtle or undetectable effects under steady-state conditions. This suggests that meaningful phenotypes may only emerge in response to environmental stressors. Our efforts focus on:
- Developing novel models of intestinal inflammation
- Generating IBD reporter zebrafish lines to study coding and non-coding IBD risk variants
- Identifying environmental factors and mechanisms that trigger aberrant immune responses in genetically susceptible hosts
- Characterizing the initiation and progression of adaptive commensal-specific T cell responses
2. Cellular and Molecular Mechanisms of Tissue Regeneration
Using unbiased analyses of immune cell composition, microbiota, and transcriptomics during intestinal inflammation and regeneration, we have identified specific immune populations, microbial species, and pathways that may promote tissue repair. Current work includes:
- Characterizing and validating candidate genes, pathways, and cell types involved in tissue regeneration
- Identifying pathways that contribute to colorectal cancer development
- Further dissecting the crosstalk between lymphocytes and epithelial cells that modulates intestinal regeneration
- Gaining mechanistic insight into how lymphocytes support epithelial barrier function
3. The Role of B Cells in Mucosal Healing and Tumorigenesis
Recent studies show that B cell accumulation in IBD and tumors. However, how B cells influence intestinal inflammation and cancer remains poorly understood. Building on our recent findings, we aim to:
- Integrate scRNA-seq and spatial transcriptomics to map clinically relevant pathways in situ
- Investigate the mechanistic and functional roles of B cells during acute and chronic inflammation as well as tumorigenesis
- Characterize the cellular circuits and heterogeneity of TLS during cancer progression
- Determine whether B cells/TLS modulate responses to ICB therapy
4. Defining the Heterogeneity of Ulcerative Colitis (UC)
Our lab previously developed an unbiased stratification of UC patients (Czarnewski et al., Nature Communications, 2019) based on transcriptomic profiles:
- UC1 patients show low response rates (~10%) to biological therapies (infliximab/vedolizumab) and elevated expression of genes associated with neutrophil degranulation and cytokine signaling.
- UC2 patients respond more favorably (~60%) and express fewer genes linked to anti-TNF therapy resistance.
To translate this classification into clinical practice, further characterization is required. Using multi-omics approaches, including single-cell and spatial transcriptomics, we aim to deeply profile the immune landscape and molecular pathways defining UC subsets. This work will provide new mechanistic insights into IBD etiology and support more personalized therapeutic strategies.
Learn More
Visit the Villablanca Lab webpage: https://villablancalab.com
Watch our research summary video: https://youtu.be/eBeMm1zHnVM
Group Members
Principal Investigators
• Eduardo Villablanca, PI
• Camilla Engblom (Group Leader, SciLifeLab), PI, Assistant Professor
• Gustavo Monasterio, PI, Assistant Professor
• Elisabeth Nyström, PI, Assistant Professor
Project Management
• Emilia Marklund, Project Manager
Postdoctoral Researchers
• Angelica Basabe
• Mora Massaro
• Yuhao Chi (Computational Biologist)
• Qianzhou Yu
• Gina Papadopoulou
PhD Students
• Katja Selin
• Francisca Castillo
• Bianca Kern
• Ali Okhovat
• Ning He (Computational Biologist)
• Johan Thorsson
• Martin Suarez (Computational Biologist)
• Alejandra Ulloa (incoming, Computational Biologist)