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Malin Flodström-Tullberg group

Etiology and pathogenesis of Type 1 Diabetes in humans - A role for enteroviruses?

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. We focus our studies on how the virus affects the infected host and the cross-talk between the virus, the immune system and the pancreatic beta cells. We are also engaged in research aiming at finding biomarkers for beta cell destruction. We expect that our studies will generate valuable information for the design of preventative treatments against islet cell destruction and type 1 diabetes.

The group also has a strong interest in the development and testing of novel prototype vaccines for enteroviruses. Moreover, we are 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

Members

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. She also holds a visiting professorship at the University of Tampere, Finland.

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.

Magdalena Mazur

Ph.D. Postdoc

Magdalena Mazur completed her Bachelor’s and Master’s degrees at Warsaw University. She did her PhD at Lund University Stem Cell Centre where she focused mostly on different aspects of pancreas development and biology. Later this continued during her post-doctoral position at AstraZeneca (Mölndal) where she was investigating novel sources of stem cells for potential diabetes treatment. In her next position as a Research Scientist in Clinical Research Centre in Malmö she was responsible was establishing a core facility for making patient-derived iPS cells. Currently, she is exploring 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 cells.

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.

Helena Sork

Ph.D., Postdoc

Helena Sork holds a Master’s degree in Biotechnology and Biomedicine from University of Tartu, Estonia. During her PhD studies at Karolinska Institutet, she concentrated mainly on the molecular characterization of extracellular vesicles by using small RNA transcriptomics and proteomics. Her current research focuses on the identification of biomarkers related to enteroviral infection and its association to Type 1 Diabetes development.

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.

Renata Utorova

M.D., Ph.D. student

Renata holds a bachelor’s degree in medicine with a major in biomedicine from Karolinska Institutet (2010) and obtained her M.D. in 2017. Her research focuses on lung and metabolic function in individuals with cystic fibrosis. She studies antiviral defense mechanisms in CF with relevance for respiratory exacerbations and cystic fibrosis-related diabetes.

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.

Kylie Burdsall

B.Sc., Fulbright Scholar

Kylie Burdsall holds a bachelors degree in Biochemistry from the University of Southern California and is a 2019-2020 U.S. Fulbright Scholar. Her current research focuses on uncovering new biomarkers indicative of virus-induced beta cell damage to better understand Type 1 Diabetes disease progression.

Projects

Type 1 diabetes is a chronic disease that results from a destruction of the insulin-producing pancreatic islet beta cells. The incidence of type 1 diabetes is increasing rapidly throughout the world. In Sweden the disease affects more than 1/200 people.

At present, there are no preventative treatments for Type 1 diabetes, and the high degree of transplant rejection and scarcity of beta cell material hampers islet replacement strategies. The accelerated incidence of Type 1 diabetes calls for the rapid development of preventative therapies.

Epidemiological data and clinical findings strongly suggest that infections with common cold viruses (mainly those by enteroviruses such as members of the Coxsackie B virus family, here denoted CVBs) can trigger the onset of Type 1 diabetes. Further knowledge on how virus infections affect the checkpoints and mechanisms that regulate the development of diabetes is needed for the design of preventative therapies.

Our studies focus on the cross-talk between the virus, the immune system and the pancreatic beta cells with an aim to provide an increased understanding for how virus infections may be involved in Type 1 diabetes. Our studies are performed with a translational approach, namely by combining basic mechanistic in vitro studies in cell lines and pancreatic islets from humans, with pathophysiological studies in human biological samples and in vivo model systems.

Past members

Soile Tuomela, Postdoc
Soile Tuomela was 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.

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.

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