Rikard Holmdahl

Rikard Holmdahl

Professor, Senior
Telephone: +46852484607
Visiting address: Solnavägen 9, 9D, 17177 Stockholm
Postal address: C2 Medicinsk biokemi och biofysik, C2 Immunologi Holmdahl, 171 77 Stockholm
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About me

  • I have an unusual background as I entered medical school on the basis of several years work in hard metal industry. I studied on evenings and succeed to be accepted at medical school at Uppsala University 1977. During the medical courses I became interested in basic research and in particular in immunology and why autoimmune diseases developed. I joined the immunology department led by Hans Wigzell 1981 and completed my PhD 1985. I completed my MD 1987 and was appointed as a docent 1987, everything at Uppsala University. After a short clinical residency career, and some shorter postdoc experiences in US, I was appointed as an associate professor at the Swedish Medical Research Council 1990. I was appointed as a full professor at Lund University 1993 and, happily for me, my entire research group joined in the move to Lund – together we formed the Medical Inflammation Research (MIR) unit at Lund University.

    At Lund University we built a platform for genetic analysis of animal models for autoimmune diseases. We were the first to positionally clone genetic polymorphism causing autoimmune diseases, the first discovery was a single nucleotide polymorphism at the Ncf1 gene causing susceptibility to autoimmune diseases in rat models. This polymorphism could later be shown to of major importance also in human autoimmune diseases and contributed to change the view on redox regulation, lack of oxidation could enhance autoimmunity. We have continued to positional clone genes and our current research is based on several of the genes that have been identified, making the focus on relevant targets for regulation of autoimmune diseases more relevant.

    In 2008 I was recruited to Karolinska Institute and was located as a professor and head of the section for medial inflammation research. We moved our research group from Lund to Stockholm. On the basis of our basic research we continued to also develop some more applied projects with the aim to enhance the diagnostic tests and developing vaccines to prevent autoimmune diseases. We have continued our genetic research with a strong focus on redox regulation in autoimmunity but we are also looking at the other side of the coin, how redox regulation could help protection against cancer.

    To be research leader also requires administrative and economic responsibilities as all research need to be self-financed and be adjusted into a university organisation. Besides this, its and important scientific responsibility, also at the international level, to defend scientific standards. But the beauty of science is still very strongly alive for me, to have the golden opportunity to make new discoveries and discuss research results with my younger coworkers and collegues.

    Ranked no 2 in Sweden in Immunology (2022 edition for the ranking of top 1000 scientists) and no 245 in the world.

Selected publications

Articles

All other publications

Grants

  • Swedish Research Council
    1 January 2020 - 31 December 2024
  • Knut and Alice Wallenberg Foundation
    1 January 2019 - 1 January 2024
  • Swedish Research Council
    1 January 2019 - 31 December 2019
  • Redoxreglering av T celler som attackerar cancer
    Swedish Cancer Society
    1 January 2018
    A long-term dream for cancer research is to be able to help the body's immune system to fight tumors. After many years of work and as a result of basic research, great successes have now come to succeed in activating the body's own T cells to attack tumors. This already has great use in tumor treatment and has given new hope to millions of people. The treatment is aimed at blocking cell molecules on the surface of the T cell which limits this activation, these are called CTLA4 and PD1. This finding stems from studies of autoimmune diseases where they have the opposite effect and treatment is now being developed to stimulate their activation. We want to explore a whole new opportunity to further activate T cells so that they can better attack tumors. We have discovered that oxygen radicals coming from macrophages in the immune system and in the tumor tissue downregulate the activity of T cells. The discovery was made through genetic studies in mice, which were subsequently confirmed in humans, and we could see that a defective gene called Ncf1 reduces the oxygen radical production, leading to more severe autoimmune disease but a strong protection against the development of cancer in mice (malignant melanoma and lung cancer). With this project we want to identify exactly in which cell and with which mechanism the redox control takes place. The aim is then to find new therapeutic possibilities where we can block the dampening effect of oxygen radicals and thereby strengthen the immune system's ability to fight tumors.
  • Swedish Research Council
    1 January 2018 - 31 December 2020
  • Swedish Research Council
    1 December 2017 - 31 December 2022
  • VINNOVA
    20 June 2017 - 19 December 2018
  • Redoxreglering av T celler som attackerar cancer
    Swedish Cancer Society
    1 January 2017
    A long-term dream for cancer research is to be able to help the body's immune system to fight tumors. After many years of work and as a result of basic research, great successes have now come to succeed in activating the body's own T cells to attack tumors. This already has great use in tumor treatment and has given new hope to millions of people. The treatment is aimed at blocking cell molecules on the surface of the T cell which limits this activation, these are called CTLA4 and PD1. This finding stems from studies of autoimmune diseases where they have the opposite effect and treatment is now being developed to stimulate their activation. We want to explore a whole new opportunity to further activate T cells so that they can better attack tumors. We have discovered that oxygen radicals coming from macrophages in the immune system and in the tumor tissue downregulate the activity of T cells. The discovery was made through genetic studies in mice, which were subsequently confirmed in humans, and we could see that a defective gene called Ncf1 reduces the oxygen radical production, leading to more severe autoimmune disease but a strong protection against the development of cancer in mice (malignant melanoma and lung cancer). With this project we want to identify exactly in which cell and with which mechanism the redox control takes place. The aim is then to find new therapeutic possibilities where we can block the dampening effect of oxygen radicals and thereby strengthen the immune system's ability to fight tumors.
  • Swedish Research Council
    1 January 2017 - 31 December 2019
  • Redoxreglering av T celler som attackerar cancer
    Swedish Cancer Society
    1 January 2016
    A long-term dream for cancer research is to be able to help the body's immune system to fight tumors. After many years of work and as a result of basic research, great successes have now come to succeed in activating the body's own T cells to attack tumors. This already has great use in tumor treatment and has given new hope to millions of people. The treatment is aimed at blocking cell molecules on the surface of the T cell which limits this activation, these are called CTLA4 and PD1. This finding stems from studies of autoimmune diseases where they have the opposite effect and treatment is now being developed to stimulate their activation. We want to explore a whole new opportunity to further activate T cells so that they can better attack tumors. We have discovered that oxygen radicals coming from macrophages in the immune system and in the tumor tissue downregulate the activity of T cells. The discovery was made through genetic studies in mice, which were subsequently confirmed in humans, and we could see that a defective gene called Ncf1 reduces the oxygen radical production, leading to more severe autoimmune disease but a strong protection against the development of cancer in mice (malignant melanoma and lung cancer). With this project we want to identify exactly in which cell and with which mechanism the redox control takes place. The aim is then to find new therapeutic possibilities where we can block the dampening effect of oxygen radicals and thereby strengthen the immune system's ability to fight tumors.
  • Swedish Research Council
    1 January 2016 - 31 December 2019
  • Swedish Research Council
    1 January 2016 - 31 December 2016
  • Swedish Research Council
    1 January 2016 - 31 December 2017
  • Does oxidation of PTPN22 regulate autoreactive T-cells?
    Swedish Foundation for Strategic Research
    1 January 2016 - 31 December 2020
  • Knut and Alice Wallenberg Foundation
    1 January 2015
    "Everyone is an expert in different parts of cancer biology, the combination of a common hypothesis and tumor model allows us to approach the problem from different but complementary directions," explains Elias Arnér, professor of biochemistry with a focus on selenium biochemistry. The project, which is supported by the Knut and Alice Wallenberg Foundation, is based on redox biology. Redox, the reduction or oxidation of molecules in the cells, are vital chemical reactions. Upon reduction, electrons are absorbed and, upon oxidation, electrons are emitted. Processes that, among other things, allow us to breathe and which give us and all living energy. But some percent of the oxygen we breathe forms reactive oxygen radicals, ROS, in the cells. These can easily react with the structures and functions of the cells, which in turn can disrupt a balance that is important to prevent disease.  - It has become increasingly clear over the years that redox processes play a major role in the functioning of cells, both in normal, healthy, cells and cancer cells. Different redox processes are important for how cancer develops, but also for how effective different cancer therapies can be. Oxidative stress Radiation and cytostatics often appear to increase oxidation in cancer cells and this is something that is good for a good treatment effect if the researchers' hypothesis is correct. - We believe that an even more effective treatment would be possible with the help of increased levels of free oxygen radicals in the cancer cells, through increased oxidation, while at the same time reducing the levels of these in immune cells. By increasing the oxidation in cancer cells, many of them would die from so-called oxidative stress, while a reduced oxidative stress in the immune system can strengthen its ability to fight the cancer cells. The trick is to gas and brake at the same time. - Oxidative stress depends on many factors, how the cell grows, its metabolism, how it is treated and how high the sugar levels are. Two birds with one stone By inhibiting the enzyme NOX2, which is found only in immune cells and not in cancer cells, the reduction in the immune cell could be increased, which could theoretically provide better protection against cancer. Another way would be to stimulate the transcription factor Nrf2, which also increases the reduction and could make the immune cells function better. - The cancer cells already have a maximum Nrf2 activity, a reduction activity at the top, and thus counteract their own already high levels of oxygen radicals. But there is another way and this is where Elias Arnér's expertise on the harness comes in. Selenium proteins that, among other things, TrxR protect the cells against free oxygen radicals and prevent them from being exposed to oxidative stress. - It is possible to inhibit the enzyme TrxR, or functions of GSH (glutathione) in the cancer cells. If you succeed in inhibiting TrxR you could hit two flies in one blow. It would increase the oxidation in cancer cells and kill them, while we believe that the reduction in normal cells would increase through stimulated activity of Nrf2, thus providing overall protection against cancer. Carefully optimistic The aim of the project is to improve existing cancer treatments and medicines, but also to develop platforms for new drugs. A decisive factor in the work is the specific mouse models and the knowledge about these, and about the redox biology in cancer, that the participating research groups have. - With the help of genetic technology we can remove important enzymes in the redox process and see what happens. We can manipulate both the cancer cells and the host's specific genes. We can also give the mice tumors and then treat them to see which method and combination of modulation of the redox processes is the most effective. The tumor forms that the researchers are working on as a model system are lung cancer and skin cancer. - But we think the principles are pretty general for most cancers. One advantage is that we, through Rolf Kiessling and his group, also have tissue from patients with skin cancer that we can use to see if conclusions and results from the mouse models are also correct in humans. Despite the massive research that is ongoing, cancer diseases continue to be the second most common cause of death after cardiovascular disease in Sweden, among others. But Elias Arnér is cautiously optimistic. - I think we are somewhat on track in this project. In general, we always get a better understanding of how cancer develops and develops, which provides better and better treatment options. Development is constantly advancing and it would be strange if medical developments would stop today. Text Carina Dahlberg Pictures Magnus Bergström Published: 2016
  • Biomarkers predicting joint inflammation
    Swedish Foundation for Strategic Research
    1 January 2015 - 31 December 2019
  • Swedish Research Council
    1 January 2015 - 31 December 2017
  • Oxidative regulation of inflammation and arthritis
    Academy of Finland
    9 January 2013 - 31 August 2017
  • Swedish Research Council
    1 January 2012 - 31 December 2012
  • Swedish Research Council
    1 January 2012 - 31 December 2012
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Employments

  • Professor, Senior, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 2025-2025
  • Professor, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 2009-2024
  • Professor, Lund University, 1994-2008

Degrees and Education

  • MD, Uppsala University Hospital, 1987
  • Docent, Med fak, Uppsala Universitet., 1987
  • PhD, Medical Biochemistry, Uppsala University, 1985

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