The Gullberg Group
Professor Donald Gullberg, originally from Sweden, did his PhD in 1990 at the Department of Medical and Physiological Chemistry, Uppsala University, Sweden, where he also worked as a researcher till 2003, apart from his postdoc period at the Molecular Biology Institute, University of California, Los Angeles in 1990–1992. He was recruited to the University of Bergen in 2004 as a professor at the Department of Biomedicine, working on collagen receptors and integrin biology, a role he currently holds as well as directing the Matrix Biology Group at the Department of Biomedicine and CCBIO. He has on different occasions had two years of research stays at the University of California, San Francisco, at the labs of Professor Valerie Weaver, Department of Surgery, and Professor Dean Sheppard, the Lung Biology Center.
Professor Gullberg’s research interests are characterizing the integrin α11β1, which is expressed on subsets of normal fibroblasts and on carcinoma-associated fibroblasts. Cells lacking α11β1 display disturbed cell-collagen interactions, altered metalloproteinase synthesis, and reduced cell proliferation.
The Matrix Biology Group in its current form was created in 2004 when Donald and Marion Kusche Gullberg started working at the UiB.
Research focus
The research in the group is focused on work related to integrin α11. The CCBIO projects deal with understanding the role of integrin α11 at the molecular and cellular levels to ultimately reach a better understanding of its role in the tumor stroma.
Projects within CCBIO
1. One focus of the CCBIO-supported activities has been to develop a new fibroblast-specific transgenic Cre driver mouse strain where Cre-recombinase is driven by a human integrin α11 promoter (ITGA11-Cre strain). Characterization of the functionality of Cre-recombinase in this mouse strain has been determined by crossing with the Rosa26R reporter strain. The first publication with this novel mouse strain was in Alam J. et al., Matrix Biol. Plus. 2020. The Cre mouse strain has now been bred with a tdTomato strain for direct visualization of ITGA11 expression.
2. A second project relates to the epitope mapping of integrin α11 monoclonal antibodies (mAbs). The Gullberg group has finished epitope mapping of mAb 210F4 and is in the final stages of mapping the epitope of the function-blocking antibody 203E1. This project was reinforced by an NCS-supported researcher, Cédric Zeltz, who started in 2022.
Future perspectives from 2024
Gullberg looks forward to taking part in seminars and conferences and contributing to common grant proposals whenever relevant and benefiting to the Matrix Biology Group’s research.
Results from the CoE period 2013-2024
Most important results
The finalization of the ITGA11-Cre mouse strain was a major milestone in the Gullberg group after 10 years of efforts on this project. Further breeding into a fluorescent reporter strain will be another step forward. The detailed epitope mapping of mAb 210F4 and mAb 203E1 to a few amino acids also illustrates the importance of consistent systematic work spanning several years to reach longlasting, well-cited results.
Most important papers
1. Romaine A. et al. Overexpression of integrin alpha11 induces cardiac fibrosis in mice. Acta Physiol (Oxf) 2018. PMID: 28771943.
2. Erusappan P et al. Integrin alpha11 cytoplasmic tail is required for FAK activation to initiate 3D cell invasion and ERK-mediated cell proliferation. Sci Rep 2019. PMID: 31653900.
3. Primac I. et al. Stromal integrin alpha11 regulates PDGFRbeta signaling and promotes breast cancer progression. J Clin Invest 2019. PMID: 31287804.
4. Zeltz C. et al. α11β1 Integrin is Induced in a Subset of Cancer-Associated Fibroblasts in Desmoplastic Tumor Stroma and Mediates In Vitro Cell Migration. Cancers 2019. PMID: 31159419.
5. Alam J. et al. Generation of a novel mouse strain with fibroblast-specific expression of Cre recombinase. Matrix Biol Plus 2020. PMID: 33543038.
6. Zeltz C. et al. Cancer-associated fibroblasts in desmoplastic tumors: emerging role of integrins. Semin Cancer Biol 2020. PMID: 31415910.
7. Sawant M. et al. Ablation of integrin-mediated cell-collagen communication alleviates fibrosis. Ann Rheum Dis 2023. PMID: 37479494.
Translational, clinical, and societal importance
The Matrix Biology Group considers itself as basic scientists, but during the past 10 years, as data have accumulated on the crucial role of integrins in remodeling the fibrotic microenvironment, they have started several collaborations using translational mouse tumor models and human clinical material with the aim to move their projects in a more clinical direction. In short term, the described project will add molecular detail to our understanding of how a subset of fibroblasts in the fibrotic stroma affects fibrosis development. In the long term, they believe the work will generate data that will significantly impact our overall knowledge on the role of integrins in fibrosis biology.
Other important outputs and achievements
The group has organized the PhD level course BMED904, Matrix Biology, which is part of the CCBIO research school. Gullberg coordinated the monthly CCBIO research seminars during 2013–2023.
CCBIO significance
Gullberg finds it intellectually stimulating to have taken part in seminars and conferences arranged by CCBIO. Financial support in the form of one 3-year PhD position, grant support and salary for a part-time technician has also been valuable at a time when other grant support was scarce.