Cecilia Söderberg-Nauclér

Cecilia Elisabet Söderberg-Nauclér, born 1967, is a professor of Medical Microbial Pathogenesis at Karolinska Institutet, Stockholm.

Education and career[]

Söderberg-Nauclér studied medicine at Karolinska Institutet 1987-1994. She was admitted as one of ten students to the doctoral program with a research focus in 1987, the second year that this education was given.The program introduced Söderberg-Nauclér early to medical research and she began researching alongside her medical studies already during the first year as a medical student. During her medical education, she was accepted as a doctoral student with Professor Erna Möller as supervisor and carried out most of her dissertation work in parallel with her medical studies. She graduated as a doctor in 1994 and defended her dissertation in 1995 with a dissertation entitled; Biological Importance and Immunogenicity of Human Aminopeptidase N (CD13) in Cytomegalovirus (CMV) Infection. The dissertation identified a receptor for the cytomegalovirus (CMV), CD13, and presented a new mechanism for virus-induced autoimmunity. She showed that CMV built cellular proteins into the envelope of the virus particle, including its receptor CD13, which then became immunogenic. Autoantibodies were produced against these proteins and could be detected in CMV infected patients who developed autoimmune complications, such as chronic graft-versus-host disease.

Söderberg-Nauclér then completed a postdoc, at the Department of Microbiology, Oregon Health Sciences University 1995-1997, with Professor Jay Nelson as mentor. The service was funded by the Wenner-Gren Foundation in Sweden, which continued to fund her research until 2003. In Portland, she continued her work studying which cells could be infected with CMV and in which cells the virus established latency. She showed that myeloid cells carry latent virus and developed the first experimental system that could reactivate latent CMV. Through an allogeneic stimulation of T cells, inflammatory cytokines were produced that differentiated monocytes into M1-type macrophages, in which reactivation could take place. This was probably the first description of M1 macrophages expressing dendritic markers. These observations were of great importance to the research field because they showed that CMV reactivation is driven by inflammation and not primarily by immunosuppression, as was thought until then, because AIDS patients and transplant patients with immunosuppressive therapy were the patients who developed severe CMV infections. Many research groups have since confirmed that inflammation drives the reactivation of latent CMV.

In 1997, Söderberg-Nauclér returned to Karolinska Institutet (KI), completed a research AT training at Huddinge Hospital and started his own research group. She became a Licensed Physician in 2001 and was recruited to the Department of Medicine and the Center for Molecular Medicine, Karolinska Hospital in 2001, when she received KI's elite investment position in Biomedical Research and a major research grant. Söderberg-Nauclér became an associate professor in Experimental Medicine in 2002. In 2004, she received the Royal Academy of Sciences' position in Medicine, which she held until 2008 when she became a professor of Medical Microbial Pathogenesis at Karolinska Institutet. At the same time, she received the Swedish Research Council's research position in Molecular Virology, which she held until 2014. Her research group Cellular and Molecular Immunology belongs to the Department of Microbial Pathogenesis at the Department of Medicine, Solna, Karolinska Institutet, for which she is head of department.

During these years, Söderberg-Nauclér further studied how CMV is reactivated in inflammation and was able to detect the virus in tissues from patients with various inflammatory disease states such as transplanted organs with rejection, in tissues from patients with inflammatory bowel disease, RA, SLE, Sjögren's Syndrome. The virus was also detected in arteriosclerotic plaques and in the aortic aneurysm. Viral activity could only be detected where active inflammation was present but not in non-inflamed tissue, suggesting inflammatory processes reactivated the virus in these disease states and her team demonstrated several mechanisms that the virus uses to drive inflammatory processes. This raises the question of whether the virus actively affects the pathogenesis of these diseases.In 2002, Dr. Charles Cobbs published in the United States that CMV could be detected in malignant brain tumors (glioblastoma). This led to a new research focus for Söderberg-Nauclér that aimed to study CMv's role in brain tumors and other cancers. Her research confirmed that CMV could be detected in 99% of glioblastomas, and also showed that virus activity was a prognostic marker of patient survival. Her research team further showed that> 90% of the childhood brain tumor Medulloblastoma and neuroblastoma were CMV positive, as well as> 90% of colon cancer, breast and ovarian cancer and also lymph node metastases and brain metastases from breast and bowel cancer. Since CMV was not detected in healthy tissue around tumors, it is now wanted to understand whether the virus plays a role in cancer and whether it can be used as a target for treatment.

Her team has identified several mechanisms that suggest that the virus plays an important role in cancer and inflammatory diseases. She has been regarded as a leading expert in this field and has lectured on the subject at many international conferences and at foreign universities. Her research has led to seven patents in CMV research and one filed patent application in SARS-CoV-2 research. Through sophisticated mechanisms and via hundreds of proteins, microRNAs and non-coding RNAs, the virus can affect cellular and immunological mechanisms that in various ways can contribute to many different inflammatory diseases and cancers. Central to the understanding of the virus' role in these diseases seems to be its ability to influence metabolic processes in cells. Projects that aim to understand how CMV affects cellular metabolism and immune metabolism are therefore today a central part of her current research work.

Since CMV has been shown to be an active infection in inflammatory diseases and cancer, she believes it is important to understand whether treatment for CMV can affect the prognosis for these patients. In animal models, her research team showed that treatment with antiviral drugs resulted in an inhibition of tumor growth by CMV positive tumors. She therefore initiated in 2006 the world's first clinical pilot study aimed at studying anti-CMV treatment in glioblastoma patients, who have a very poor prognosis. The study was published in 2013 and was undersized to show the effect of the drug, but there was some indication that those treated with the anti-CMV drug had a better survival. At follow-up of these and additional treated patients, an improvement in the survival of 102 glioblastoma patients treated with anti-CMV medication (valganciclovir) was shown in addition to their standard treatment. Mean survival increased from 13.5 to 24.1 months in those receiving valganciclovir and two-year survival increased from 18% to 49.5% (CCR). In those who received optimal tumor treatment and anti-CMV medication, the mean survival was 29.7 months and the 2-year survival was 64%. With support from the Swedish Research Council, her team is now conducting a randomized double-blind study that aims to confirm whether this treatment positively affects glioblastoma patients' prognosis or not. The study is being carried out in Sweden and will open soon in Norway and Italy. 220 patients are planned to be included and will be important in investigating whether a targeted treatment for CMV can become part of future oncology treatment for CMV positive tumors.

SARS-CoV-2 Pandemic[]

During the Corona Pandemic, Söderberg-Nauclér considered that the Swedish Public Health Agency and the Swedish government did not act on scientific data on the infectious nature of the coronavirus. She considered that one should act according to the precautionary principle and take measures based on available scientific data that showed that the virus is transmitted before becoming ill, that some individuals do not even develop symptoms but can still spread infection, that SARS-CoV-2 is partly an airborne infection and that mouth guards limit infection. She advocated mass testing, infection tracing and quarantine of infection contacts and family members to limit the spread of the epidemic. She considered early on that children are contagious and that schools are an important part of the spread of infection, and that further measures are needed to reduce the number of deaths in Covid19 and to avoid organ damage and long-covid in a significant proportion of the population. At an early stage, she advocated stronger measures to limit infection, and she and her colleagues warned on 15 March 2020 that healthcare was facing collapse if measures were not taken. Measures came from the government on 16 March. After that, it became Sweden's strategy to slowly infect the population so that the health service would be able to take care of those who became ill. Before she and her colleagues sounded the alarm, the Public Health Agency or the Government had not paid attention to this fact.

Söderberg-Nauclér has debated these issues in national and international media and has received criticism for her commitment to Sweden's strategy, despite the fact that her views are in line with international infection control organizations such as the ECDC and CDC and the WHO's attitude to these issues. Together with colleagues with similar views, Veteskapsforum Covid19 was founded, which aims to contribute through scientific data to increased knowledge about the SARS-CoV-2 virus and its effects on the individual and society. She has participated in Vetcov19's podcast Sunday Sofa on several occasions and dealt with topics related to SARS-CoV-2 and its disease panorama, long-covid and COVID vaccinations. Over the past year, she has been researching pre-immunity and discovered that the flu can provide a cross-immunity that can provide protection against SARS-CoV-2 infection. Together with mathematician Marcus Carlsson in Lund, she has modeled different scenarios for the spread of infection in Sweden and the world based on these conditions, and they have been able to describe the pandemic's development in different cities with very good precision.

Selected publications[]

• Hansson, Göran K.; Robertson, Anna-Karin L.; Söderberg-Nauclér, Cecilia (2006-01-24). "Inflammation and atherosclerosis". Annual Review of Pathology: Mechanisms of Disease. 1 (1): 297–329. doi:10.1146/annurev.pathol.1.110304.100100. ISSN 1553-4006. PMID 18039117.
• Söderberg-Nauclér, Cecilia; Fish, Kenneth N.; Nelson, Jay A. (1997-10-03). "Reactivation of Latent Human Cytomegalovirus by Allogeneic Stimulation of Blood Cells from Healthy Donors". Cell. 91 (1): 119–126. doi:10.1016/S0092-8674(01)80014-3. ISSN 0092-8674. PMID 9335340. S2CID 11028979.
• Soderberg-Naucler, C.; Streblow, D. N.; Fish, K. N.; Allan-Yorke, J.; Smith, P. P.; Nelson, J. A. (2001-08-15). "Reactivation of Latent Human Cytomegalovirus in CD14+ Monocytes Is Differentiation Dependent". Journal of Virology. 75 (16): 7543–7554. doi:10.1128/jvi.75.16.7543-7554.2001. ISSN 0022-538X. PMC 114989. PMID 11462026.

References[]

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