The role of immune system in select inflammatory disorders, infectious diseases and cancer. The main goal of the research is to understand the function of the immune system – as we still lack the full understanding of it.
About the group
The research about the immune system includes projects that could be of great interest for dental research community in the future, as the whole immune system is located or develops from structures in oral tissues.
We can distinguish: 1) tonsil, which is a part of the peripheral immune system (being a particular collection of lymph nodes), 2) the bone marrow of, for example, the jaw bone, which is a central part of the immune system holding stem cells that give rise to the whole immune system, where B lymphocytes develop (and learn B-cell tolerance), and where plasma cells home to produce antibodies, and 3) the thymus, which is also a part of the central immune system that develops from 3-4 pharyngeal pouch (in which T cells develop and learn self-tolerance).
The objectives are to better understand risk factors in cancer development related to the immune system failure to eradicate cancer cells. The factors can be divided into innate (pro- and anti-inflammation) and adaptive (T-cell tolerance, T regulatory cells, and cytokines) immunity risks. We pursue observations with which we could gain the understanding of the initiation of the immune response as well as its regulation that would benefit cancer research.
We plan to type DNA mutations (and polymorphisms) in genes important for innate immunity like the Toll-like receptors, various cytokines and correlate them with various diseases like cancer (breast, neuroendocrine tumors of gastrointestinal tract and sarcomas), respiratory infectious diseases (tuberculosis) and other inflammatory disorders (primary osteoarthritis of hip and knee) in case-control studies. Regarding the latter, it is known that proinflammatory cytokines can lead to destruction of soft and hard joint tissue. Despite this knowledge, the primary osteoarthritis still lacks comprehension of its full etiology, and we hope that we can contribute to it by searching for inflammation-associated risk factors in this complex genetic disease.
The above-mentioned projects involve collaborations with hospitals in Norway and Croatia (Zagreb and Rijeka) and with a scientific institution Rudjer Boskovic Institute (Zagreb). We also wish to collaborate with clinical research groups in other European countries including Austria, Germany and Italy.
A) The genetics and epigenetics of cancer (breast, neuroendocrine tumors of gastrointestinal tract and sarcomas) should be accomplished with collaborations in Norway and in some EU countries (Croatia, Austria, Germany and Italy). The research deals with hallmarks of cancer – especially the two immune-related ones: immune-cell attack avoidance and inflammation as a tumor-promoter. We currently search for genetic risk factors using various cellular and molecular (microchip and Next Gen Sequencing) technologies including RNA (exome and non-coding) analyses and polymorphic DNA typing of select genes (Randy Krog Eftedal, Anne Karin Kristoffersen, & Marie Wika).
B) The genetics of osteoarthritis - the primary one with its risks for development in temporo-mandibular joint. We wish to assess the risks in this disease and compare them with risks from other sites. It is a long-term project that has yielded results firstly in large joints like hip and knee. We are currently investigating the roles of proinflammatory and anti-inflammatory factors as well as select microRNAs that can regulate them, by using the short-term culture method (Randi Krog Eftedal, & Ngoc Ky Cuong Khuu).
C) The genetics and epigenetics of chronic periodontitis has been investigated with collaborations within the Faculty of Dentistry in Oslo. The plan is to continue working on risks which influence development of the disease. We plan to continue working on this project in collaboration with Morten Enersen's group at IOB (Anne Karin Kristoffersen).