Malin Flodström-Tullberg group - Etiology and pathogenesis of type 1 diabetes

Infections with common viruses (e.g. Coxsackieviruses) have been linked to type 1 diabetes development in humans. Our present research seeks to define the role of the virus in the disease process.

A group of people on black background.
Maln Flodström Tullberg research group. Photo: Peter Holgersson/private

About our research

Type 1 diabetes is the most common, chronic and life-threatening disease in children. About 1/200 people suffer from the disease in Sweden. Malin Flodström-Tullberg's research group focuses on understanding the etiology and pathogenesis of the disease. The research group is engaged in finding disease causes and contributing to the development and preclinical testing of new disease interventions.

The group studies genetic, environmental and pancreatic beta cell intrinsic factors and how these affect the immune system and contribute to disease development. Of particular interest is the role of the environment including microbial diversity and infections with common viruses, so-called enteroviruses, in the disease process. The group has participated in the generation of and performed preclinical tests of new enterovirus vaccines which are now in phase I trials. In recent years, the group has become interested in disease biomarkers, in particular non-invasive measures to detect beta cell damage, and has built a strong platform for such studies.

The group is also studying altered endocrine and immune functions in the disease Cystic Fibrosis.

Keywords:
Autoimmunity, Beta cell, Coxsackievirus, Enterovirus, Innate immunity, Cystic Fibrosis, Insulin, Interferon, Islets of Langerhans, Protease, Translational Research, Type 1 Diabetes, Vaccine, Virus

Group leader

Malin Flodström Tullberg

Group Leader, Ph.D. Professor

Dr. Malin Flodström Tullberg was recruited to Karolinska Institutet in 2003. She holds a Ph.D. degree in Medical Cell Biology from Uppsala University, Sweden (1998), and did a postdoc in immunology at The Scripps Research Institute, La Jolla, USA (1998-2003). Besides being professor and group leader, she is serving as deputy unit head for the Center for Infectious Medicine.

Malin Flodström-Tullberg about her research

Lab members

Virginia Stone

Ph.D. Assistant Professor

Virginia Stone has a bachelors degree in Molecular Biology and Biochemistry from Durham University, England. She holds a Ph.D.from the Peninsula College of Medicine and Dentistry, Devon (2013). Her research now involves the possible mechanisms through which enteroviruses may contribute to the development and pathogenesis of Type 1 diabetes, with a particular focus on the gut.

Emma Ringqivst

Ph.D., Research coordinator

Emma Ringqivst received her PhD from Uppsala University in 2010 on host-parasite interactions during Giardia infections. Over several postdoc positions she changed fields to helminth infection responses and pulmonary medicine and immunology (Massey university/ New Zealand, University of Edinburgh/Scotland, and Karolinska institutet). The last couple of years she focused on human neonate pulmonary development and immunology, and specifically the ontogeny, development and function of pulmonary macrophages and their link to adult respiratory disease, eg. BPD and COPD. Emma assists with techniques and coordinates the immunological research into type-1 diabetes within the Flodström-Tullberg research group.

Isabel Diaz Lozano

M.Sc. Ph.D. Postdoc

Isabel Maria Diaz Lozano holds a bachelor degree in Biology and master degree in Biotechnology from University of Granada, Spain. She completed her Ph.D. in Fundamental and Systems Biology at the University of Granada in December 2016. Her thesis work focused on specific proteins carried within exovesicles released from the protozoan parasite T. cruzi and their relation to disease pathogenesis. She also explored the use of exovesicles as markers of Chagas disease. Currently, her research involves the search for new biomarkers that relate to infections by enteroviruses and the development of type 1 diabetes. A special focus is to perform proteomic and transcriptomic studies on extracellular vesicles released in experimental model systems.

Anirudra Parajuli

Postdoctoral studies

Anirudra Parajuli has a bachelor’s degree in Pharmaceutical Science from Pokhara University, Nepal. He did his Masters in Pharmaceutical biotechnology and PhD in Environmental ecology (Microbiology) at the University of Helsinki, Finland. In his PhD thesis, he investigated interactions between the microbiota in the living environment and the composition of the human gut microbiota. In his current research Anirudra is focusing on understanding the way genetic and environmental factors, including the living environment, regulate the risk for Type 1 Diabetes development.

Marta Butrym

M.Sc., Ph.D Student

Marta Butrym holds a Master’s degree in Biology from University of Warsaw, Poland. She has both academic and industry experience and has previously contributed to the pre-clinical evaluation of an antimicrobial and anti-inflammatory peptide as a drug candidate and medical device active component. Currently, she is working on in vitro and in vivo models to examine whether new enterovirus vaccines and antiviral treatments can prevent infections and clinically relevant diseases induced by enterovirus infections including type 1 diabetes.

Selina Parvin

Laboratory Technician

Selina Parvin is a skilled laboratory technician who has worked at Karolinska Institutet for several years and before that at Uppsala University. Selina joined the Flodström-Tullberg group in 2020 and has responsibility for genotyping, tissue sectioning, histology and cell culture work. 

Martha Castro

Fulbright Scholar

Martha Castro received her Bachelor’s degree in Molecular Biology from Pomona College, United States. As a Fulbright Scholar, she is working to identify biomarkers for enterovirus-induced damage to pancreatic beta cells and to further characterize the role of viral infection in type I diabetes pathogenesis. 

Open positions

We are always interested in recruiting talented PhD students and postdoctoral fellows.
Please feel free to contact Dr. Malin Flodström Tullberg for further information on current opportunities.

Past members

Magdalena Mazur, Ph.D., Research Coordinator
Magdalena Mazur coordinated research related to finding novel ways to study the etiology and pathogenesis of type 1 diabetes, with specific focus on viral infections and their impact on the pancreatic beta cell. 

Kylie Burdsall, Fulbright Scholar
Kylie Burdsall was a U.S. Fulbright Scholar in the Flodström-Tullberg group in 2019-2020. She focused on uncovering new biomarkers indicative of virus-induced cell damage to better understand type 1 diabetes disease progression.

Renata Utorova, Ph.D. 
Renata defended her licentiate degree in 2020 on antiviral defence mechanisms in CF with relevance for respiratory exacerbations and cystic-fibrosis related diabetes. 

Helena Sork, Postdoc
Helena Sork did a postdoc in the Flodström-Tullberg group during the years 2018-2019 and worked on the identification of biomarkers related to enterovirus infection and its association to type 1 diabetes development.

Soile Tuomela, Postdoc
Soile Tuomela's postdoc period was funded by the Novo Nordisk Postdoctoral Fellowship Program at Karolinska Institutet. Her studies included the identification of enterovirus peptides presented by pancreatic beta cells via MHC class I. She was also involved in examining the role of genetic polymorphism in the development of Type 1 Diabetes.

Sebastian Kapell, Ph.D.
Sebastian Kapell defended his thesis in 2019. He was involved in research that focuses on describing the mechanisms by which an enterovirus modulates the function of the insulin secreting beta cell and how this relates to innate immunity.

Erna Domsgen, Postdoc
Erna Domsgen did her postdoc in the group until 2017. She was engaged in studies related to the host immune response to picornaviruses and how such viruses evade the innate immune response.

Emma Svedin, Ph.D.
Emma Svedin presented her thesis in 2017. Her Ph.D. studies included aspects of how enterovirus infections result in impaired beta cell functions. She was also studying why patients with cystic fibrosis have a decreased ability to clear viral and bacterial infections.

Pär Larsson, Ph.D.
Pär Larsson worked on the mechanisms that regulate susceptibility to enterovirus-induced type 1 diabetes and with the development and testing of an enterovirus vaccine. He defended his thesis in 2014.

Katharina Lind, Ph.D.
Katharina Lind defended her thesis in 2014. The aims of her Ph.D. studies were to determine how the host cell recognizes enteroviruses, how enteroviruses evade the host immune system and to investigate the role of type III interferons in the host immune response to enterovirus infections.

Olli Laitinen, Ph.D., Senior Researcher
Olli Laitinen worked on projects aiming at unravelling the mechanisms by which enteroviruses cause pancreatic beta cell damage. This work involved the development of new tools to study virus-host interactions.

Terezia Pincikova, M.D., Ph.D.
Terezia Pincikova studied the impact of vitamin D supplementation on the immune response and on glucose tolerance in cystic fibrosis, and defended her thesis in 2014. The results of her research suggest that vitamin D exerts a complex immunomodulatory effect which may be clinically beneficial for cystic fibrosis patients.

Lakshmikanth Tadepally, Ph.D. Senior Research Fellow
During the years 2010-2012 Lakshmikanth Tadepally worked as a Senior postdoctoral fellow in the Flodström-Tullberg lab on a vaccine development project in collaboration with Vactech Oy, Finland and Sanofi Pasteur, France. His contributions included the first preclinical safety testing of a Coxsackievirus B1 vaccine in NOD mice.

Michael Hühn, Ph.D.
Michael Hühn studied different aspects of the innate immune response to enteroviruses and defended his thesis in 2010. Among other things he demonstrated that the gene ifih1 (mda5) is crucial for the successful host response to enterovirus infections.

Stella Jacobson, Ph.D.
Stella Jacobson was working in the field of transplantation immunology and was the first to show that mesenchymal stromal cells provide protection from allograft rejection. She defended her thesis in 2010.

Monica Hultcrantz, Ph.D.
Monica Hultcrantz defended her thesis on the role of interferons in type 1 diabetes in 2008. One of her major contributions was to show how the pancreatic beta cell regulate type 1 diabetes development by responding to proinflammatory cytokines.

Collaborations

National, Karolinska Institutet

  • Karin Loré, Department of Medicine Solna, Karolinska Institutet
  • Lena Hjelte, Stockholm Cystic Fibrosis Centre, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
  • Nagihan Bostanci, Department of Dental Medicine, Karolinska Institutet
  • Samir El Andaloussi, Department of Laboratory Medicine, Karolinska Institutet
  • Susanne Gabrielsson, Department of Medicine Solna, Karolinska Institutet

National, others

  • Lena Eliasson, Department of Clinical Sciences, Lund University

International

  • Aki Sinkkonen, University of Helsinki, Finland
  • Charles Rice, Rockefeller University, New York, US
  • Heikki Hyöty, University of Tampere, Finland
  • Ivan Gerling, University of Tennessee, US
  • Minna Hankaniemi, University of Tampere, Finland
  • Noel Morgan, University of Exeter, UK
  • Roberto Mallone, Institut Cochine, Paris, France
  • Sarah Richardson, University of Exeter, UK
  • Varpu Marjumäki, University of Jyväskylä, Finland
  • Vesa Hytönen, University of Tampere, Finland

Network for Pancreatic Organ Donors with Diabetes

nPOD-virus group

Projects

The group is actively running several projects, many of which are in collaboration with other national and international research groups.

The main projects are the following:

  • The role of interferons in the pathogenesis of type 1 diabetes
  • Defining the mechanism behind Coxsackievirus induced pancreatic beta cell damage and discovering new biomarkers for type 1 diabetes
  • Development and testing of enterovirus vaccines and antivirals
  • Understanding altered endocrine and immune functions in Cystic Fibrosis