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. The CCBIO projects deal with understanding the role of integrin α11 at the molecular and cellular levels in order to ultimately reach a better understanding of its role in the tumor stroma.
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 3kb of 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 published in 2020 in Matrix Biology Plus (Alam J. et al., Matrix Biol. Plus, 2020). The Cre mouse strain is now being bred with a tdTomato strain for direct visualization.
2. A second CCBIO-supported project relates to the role of integrin α11 in skin squamous cell carcinoma (SCC) and is performed in collaboration with Ritva Heljasvaara, University of Oulu. Focus is on analyzing the role of dermal stroma in a mouse model of SCC using the mouse strain deficient in integrin α11. Due to the COVID situation, this project has been dormant, but as of January 2021, it has been activated by a collaboration with Daniela Costea (CCBIO, UiB) and Vel-Matti Kähäri, University of Turku. The idea is to complement the animal data with imaging mass cytometry data (Hyperion) from SCC material obtained from Finland.
3. A third project relates to epitope mapping of integrin α11 mAbs. The group has finished epitope mapping of mAb210F4 but is continuing with the function blocking antibody mAb203E1. This project is now reinforced by a PhD student financed by the Medical Faculty and a Norwegian Cancer Society supported postdoc who will start in 2022.
The finalization of the ITGA11-Cre mouse strain was a major milestone after 10 years of systematic work on this project. The detailed epitope mapping of mAb210F4 down to five amino acids also reflected persistent work on this project over a number of years.
Major challenges include finding funding for the projects, finding good candidates for MS, PhD and postdoc positions, and the restricted traveling situation, hampering active collaborations that would have benefitted from interactions of laboratory personnel.
The overall goal is to continue characterization of integrin α11 to be able to evaluate its potential as a therapeutic target in fibrotic conditions, specifically:
1. Together with Ritva Heljasvaara, the group is crossing the ITGA11-Cre mouse strain with the doublefluorescent ROSAmT/mG reporter strain (Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo, https://www.jax. org/strain/007576) which will enable direct visualization of the dynamic α11 expression in tissues and tumor stroma without fixation or other treatments.
2. For the function blocking α11 mAb203E1 antibody, the group continues epitope mapping. They have sequenced the antibody and would now like to humanize the antibody, which is a costly project, but resources will be applied for.
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.