Spatial transcriptomics to predict treatment response in Crohn’s disease

Spatial transcriptomics to predict treatment response in Crohn’s disease (PI Espen Bækkevold)

Anti-TNF therapy is currently the first treatment choice for newly diagnosed patients with Crohn’s disease (CD). However, approximately 30% of CD patients have no effect of anti-TNF therapy, and because there are no clinical criteria to identify non-responders, all patients are initially given such treatment. The aim of this project is to identify biomarkers that with high accuracy predict which patients that will fail anti-TNF treatment. Clinical implementation of such biomarkers will personalize the treatment of CD with significant health benefits.
To untangle the cellular networks associated with durable remission upon anti-TNF therapy, we will take advantage of the most recent advances in experimental and computational methods and study the disease process in CD-lesions with two complementary high dimensional techniques:
1) Analyses of datasets from single-cell RNA sequencing (scRNAseq) of tissue-derived cells from inflamed and health intestine will give an unbiased characterization of the gene expression levels of all cells, and 2) the Spatial Transcriptomics (ST) method will reveal the spatial pattern of gene expression levels within the tissue.
Advanced bioinformatics to integrate the two methods will give unbiased and comprehensive tissue maps with unprecedented molecular resolution.
Based on this analysis we will construct a single cell transcriptome atlas with spatial information across tissues from both anti-TNF responders and non-responders. This will give a unique possibility to identify differences at the cellular and molecular level in time and space in the search for predictive biomarkers for treatment response.

Flow cytometry analysis of macrophages (macs) isolated from Crohn’s disease lesions (obtained by colonoscopy, right image) and adjacent uninflamed mucosa showing a large expansion of inflammatory macrophages in the lesions.

Frode Jahnsen (Group leader)

Frode is professor of medicine at the University of Oslo and senior consultant in clinical gastrointestinal pathology. He obtained his PhD in immunology under the supervision of Prof. Per Brandtzæg’s lab in 1997. He did a postdoc partly in the Brandtzæg lab and partly in Pat Holt’s lab in Perth, Australia. Returning from Australia in 2001 he started his training in Pathology and at the same time started to build his own research group. He became group leader in Centre for Immune Regulation (CIR), a Centre of Excellence funded by The Norwegian Research Council from 2007-2017. Until 2015 the lab had particular focus on immunopathology in allergic diseases in the airways. However, over the last 6 years the focus has shifted to mucosal immunology in the gut, and currently the lab has several ongoing projects studying the immune system in the gut in health as well as in diseases such as celiac disease, inflammatory bowel disease, graft versus host disease, Hirschsprung disease, and colorectal cancer.

Tuva Høst Brunsell (Postdoc)

Tuva started in January 2021 in a shared position as a pathologist in training and a postdoc in the lab. After completing her medical studies and internship she obtained a PhD focusing on the genomics of colorectal liver metastases at the Department of Molecular Oncology, Institute of Cancer Research. She is now establishing a method of high-resolution spatial transcriptomics in our lab which will be used to study immune cells in a morphological context in normal intestine and colorectal cancer.

Espen Bækkevold (Researcher)

Espen is molecular cell biologist and has a PhD in immunology from the University of Oslo. Following a postdoc at Harvard Medical School and Boston Children’s Hospital and a researcher appointment at the Norwegian School of Veterinary Science, he joined the lab in 2007. He is also a Professor at the Faculty of Dentistry, University of Oslo.
Espen has a “wet lab” background, and is interested in applying single-cell technologies to understand the composition and development of immune cell networks in human mucosal tissues.

Raquel Bartolome Casado (Postdoc)

Raquel is interested in studying the immune cells that are lodged in the human intestinal mucosa at single-cell resolution. After obtaining her degree in Biotechnology at the University of Salamanca (Spain), Raquel worked at the Cancer Research Center in Salamanca and completed her MSc studies. While working in this project, she realized research stays at the lab of Prof. Fritjof Lund-Johansen at the University of Oslo, where she acquired experience in novel multiplex bead-based immunoassays for large scale proteomic analysis. Then, Raquel went on to do her PhD in Prof. Frode Jahnsen’s lab at the Faculty of Medicine, University of Oslo. Her PhD work was focused on the longevity of the adaptive immune cell compartment in the human small intestine, with special focus on characterizing resident memory CD8+ and CD4+ T cells. Raquel obtained a Three-year Researcher Project grant with International Mobility from the Research Council of Norway and recently joined the Teichmann lab at Wellcome Sanger Institute (Cambridge, UK). She is currently studying the development and long-term maintenance of resident memory T cells in the human gut using single-cell multi-omics approaches.

Madeleine Chouliara (Postdoc)

Madeleine got a BSc in Physics from the University of Athens and an MSc in Applied Physics with a specialization in Photonics and Quantum Optics from the University of Strathclyde. She will receive her Ph.D. in Physical Chemistry from Lund University in September 2022. During her PhD, she studied the binding kinetics of protein-protein interactions between receptors presented on the surface of T cells and protein-functionalized supported lipid bilayers using fluorescence microscopy. She has also worked as an early-stage researcher at the University of Murcia where she developed optical systems in the field of adaptive optics for biomedical applications while collaborating with Zeiss. After that, she worked as a research assistant at the Technical University of Denmark in the development of optical trapping systems for drug delivery purposes in partnership with Novo Nordisk. 

Diana Domanska (Researcher)

Diana is a bioinformatician and matematician. She received her PhD in computer science from University of Silesia in Katowice (Poland) in 2014. After PhD, she did her postdoc at the University in Oslo in Biomedical Informatics. She worked on statistical analysis of genomics data, interactive visualizations and method development for genome-wide studies. She joined the lab in 2019, where she started working with single cell data and spatial transcriptomics. Current interests are in methods development for genomic data and their analysis.

Kjersti Thorvaldsen Hagen (Laboratory Scientist)

Kjersti is a biomedical laboratory scientist from Oslo Metropolitan University, and Kjersti joined the lab in 2008. Her main expertise is immunohistochemistry- and immunofluorescence methods. She also has genuine interests in molecular biology, especially in the working methods in single cell technologies.

Hanna Johannessen (PhD student)

Hanna joined the lab in February 2021 after completing her medical studies at the University of Oslo. Hanna is interested in the development of the mucosal immune system in the gut and in her PhD project she studies the relationship between the enteric nervous system and the immune system of children with Hirschsprungs disease. Her studies also include clinical aspects of Hirschsprungs disease, and she has collaborate closely with the pediatric surgeons at Oslo University Hospital.

Victoria Therese Karlsen (PhD student)

Victoria joined the lab in 2019 for her Master’s project, characterizing macrophages in the human colonic mucosa, and is now a PhD candidate in the group. Victoria is interested in the human intestinal immune system and in her PhD project she aims to identify molecular hubs and signaling pathways in the tumor microenvironment of colorectal liver metastases that are targetable for anti-cancer treatment.