Professor Donald Gullberg has his background in medical chemistry from Uppsala University, and has been working on collagen receptors and integrin biology. He was recruited to the University of Bergen in 2004 and is now directing the Matrix Biology Group at the Department of Biomedicine.
The research of the Gullberg group is focused on work related to integrin α11. Integrin α11β1 is a collagen receptor with several features which makes it an interesting molecule in tissue and tumor fibrosis. During almost two decades, the group has accumulated a number of reagents to perform detailed molecular studies of cell-collagen interactions, including several unique transgenic mouse strains all based on the integrin α11 gene. During 2020, a model will be published on the ITGA11-Cre transgenic mouse strain.
The group’s projects
The CCBIO projects deal with deeper knowledge on the role of integrin α11 at the molecular and cellular level in order to better understand its role in the tumor stroma.
1. The major focus has been to develop a new fibroblast specific transgenic Cre driver mouse strain where Crerecombinase is driven by 3kb of human integrin α11 promoter (ITGA11-Cre strain). Functional characterization of Cre-recombinase in this mouse strain has been determined by crossing with the Rosa 26 Cre reporter strain.
2. A second project relates to the role of integrin α11 in squamous cell carcinoma and is performed in collaboration with Ritva Heljasvaara, University of Oulu. Dr. Heljasvaara is a member of the International Faculty.
3. A third project has just started and will be performed in collaboration with Daniela Costea. This will involve studies of integrin α11 regulation in cancer associated fibroblasts (CAFs) by mechanical stiffness and use of the Hyperion Imaging System to visualize CAF biomarkers in the tumor microenvironment (TME).
During 2019, the group has published one paper describing the wide distribution of α11 on CAFs in different solid tumors, and a detailed paper describing the importance of integrin α11 cytoplasmic tail for ERK-mediated α11β1 cell signaling. An extensive study, resulting from a productive and stimulating collaboration with Agnés Noël, University of Liege, on the role of α11β1 in the PyMT breast cancer model, was also published in 2019.
Plans for the future
1.With regard to the ITGA11-Cre mouse strain, the plan is to cross it with a R26R dtTomato mouse strain.
2. The mechanical strain experiments involve mutant CAFs lacking integrin α5, mutant mammary fibroblasts lacking TGFβRII, and syndecan-4-deficient MEFs. The group has observed interesting phenotypes of mutant fibroblasts cultured on surfaces of different stiffness and is in the process of re-transfecting TGFβRII and syndecan-4 to ensure the specificity of the observed effects.
3. The work to further characterize α11 antibodies continue as planned, and epitope mapping of α11 antibodies using mutant integrin α11 variants (domain swapping and deletions) expressed in HEK293 cells are ongoing.
Current challenges in the field
In basic integrin research, major questions concern a better and more detailed understanding of molecular mechanisms of integrin function as well as the nature of synergistic integrin activities in biological systems. In the fibrosis field, the challenge is to understand heterogeneity of fibroblasts and CAFs in the tumor stroma as well as the mechanisms that affect the dynamics of different fibroblast states.
Spring 2016 Interview
Professor Gullberg is directing the Matrix Biology Group at the Department of Biomedicine at UiB. The Gullberg group was the one to discover integrin α11, and they continue to explore the possibilities in this area.
What is the main emphasis of your research?
"We are interested in basic mechanisms of how connective tissue cells interact with the fibrillar protein collagen. In various projects it has become increasingly clear that both wound healing, scarring and solid tumor growth and spread, share some common mechanisms at the molecular level. We currently have funding to pursue projects related to fibrosis (scarring) and the tumor microenvironment (TME)."
Your projects focus on integrin α11, can you tell us more about the significance of this integrin?
"Integrin alpha11 is a collagen receptor that was identified in my laboratory 20 years ago, and amazingly enough it keeps challenging us as we try to understand what it does. We have learned some basic things about this receptor in the time that we have been acquainted. It mediates cell adhesion and cell migration on collagen, and it reorganizes collagen to make it more compact. In certain lung tumors it conditions the TME so that tumors grow and spread more."
Can you describe your 2015 researchprojects and your findings?
"Within the framework of CCBIO, two major projects have been pursued in 2015. Firstly, generation and characterization of monoclonal antibodies, Moabs, recognizing human integrin alpha 11 together with a German company, Nanotools. Secondly, generation and characterization of a new transgenic mouse strain with the potential to serve as a tool for conditionally deleting cancer-associated fibroblasts (CAFs) in the stroma of experimental tumors."
Find Gullberg's PubMed publication list here.