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Centre for Cancer Biomarkers CCBIO

Matrix Biology

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 where he is collaborating closely with Marion Kusche-Gullberg (proteoglycan-related research), Rolf K. Reed (physiology) and Linda Stuhr (physiology).

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Donald Gullberg in the laboratory.
Photo:
Ingvild Melien

Since the 1990s, projects have been focused on integrin α11, which was previously discovered in the Gullberg group. Integrin α11beta1 is a collagen receptor with a number of features which makes it a key molecule in tissue fibrosis and tumor-stroma interactions in different types of solid tumors. The group has  generated new animal models (mouse and zebrafish) to study the role of integrin α11 during development, in fibrosis and in tumors, and reached a better understanding of the role of integrin α11 in cancer-associated fibroblasts (Marie Curie ITN funded project).

The CCBIO projects deals with the role of integrin α11 in tumor stroma using:

a) tumor-fibroblast heterospheroids as a 3D model system to understand bidirectional communication between tumor cells and fibroblasts; a long-term aim is to develop this system to a large scale in vitro assay to screen for compounds targeting integrins/integrin signalling and with the potential to inhibit tumor growth and spread:

 b) new reagents/animal models to conditionally inactivate genes in an integrin α11 specific manner. The long-term aim is to develop new animal models to better analyze the role of cancer associated fibroblasts in tumor stroma interactions.

During 2014, a mouse strain enabling conditional inactivation of integrin α11 has been successfully generated, and a mouse strain for studies of the tumor stroma is currently being analyzed. Two major efforts to generate mouse monoclonal antibodies against α11 are ongoing, and the group will determine the role of integrin α11 during EMT using human lung cancer cells and mouse mammary gland epithelial cells. 

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."

PubMed Publications