Tim Willinger group
Our research group studies immune responses in mucosal tissues and the interaction between the immune system and commensal microbes (microbiota) in the context of health and disease.
Mucosal tissues, such as the gut and lung, harbor large numbers of commensal microbes that outnumber host cells by a factor of 10. During evolution a symbiotic relationship has developed between the microbiota and the immune system. This symbiosis is critical for many physiological processes of the host, such as nutrient metabolism, tissue development, and host defense.
Mouse studies have implicated disturbed immune system-microbiota crosstalk in local and systemic inflammation. However, not much is known about this crosstalk in humans and its contribution to inflammatory diseases. Novel experimental systems are required to investigate the human immune-microbiota crosstalk since the immune system, inflammatory responses, and microbiota differ between mice and humans.
We aim to dissect how the immune system maintains gut and lung homeostasis and how disturbed immune-microbiota crosstalk causes tissue inflammation. To achieve our research aims, we are using innovative models with direct human relevance that allow experimental modulation of the immune system and the microbiota. Our multidisciplinary approach involves in vivo models, advanced immunological techniques, and systems biology analyses, such as multi-parameter flow cytometry, mass cytometry (CyTOF), confocal microscopy, and next-generation sequencing.
Understanding the interplay of the immune system with the microbiota has great potential to develop novel strategies for the treatment of human diseases. Our research aims to open a new avenue of translational research that is complementary to clinical studies.
- Identification of novel factors that regulate the immune-microbiota crosstalk
- Interaction of human monocytes and macrophages with the microbiota
- Immune system-microbiota crosstalk in human inflammatory bowel disease (IBD)
- Role of G protein-coupled receptors and immune cell positioning in gut homeostasis
- Role of human monocytes/macrophages in lung homeostasis and inflammation
Center for Innovative Medicine (CIMED), Karolinska Institutet/SLL
Swedish Research Council (Vetenskapsrådet)
Åke Wibergs Stiftelse
European Union (Horizon 2020)
At Karolinska Institutet:
- Prof. Lennart Hammarström (Department of Laboratory Medicine)
- Prof. Johan Sandberg (Center for Infectious Medicine)
- Prof. Magnus Sköld (Department of Medicine, Solna)
- Prof. Magnus Westgren (Department of Clinical Science, Intervention and Technology)
- Dr. Niklas Björkström (Center for Infectious Medicine)
- Dr. Cecilia Götherström (Center for Hematology and Regenerative Medicine)
- Dr. Charlotte Hedin (Gastrocentrum)
- Dr. Anna Smed Sörensen (Department of Medicine, Solna)
- Dr. Eduardo Villablanca (Department of Medicine, Solna)
- Prof. Richard Flavell (Yale University)
- Dr. Joao Pereira (Yale University)
- Prof. Gérard Eberl (Pasteur Institute Paris)
- Prof. Samuel Huber (University Medical Center Hamburg)
- Dr. Marcel de Zoete (Utrecht University)
Tim Willinger, MD, PhD, Group Leader
He was awarded a PhD in 2006 for his work on human T cell memory in the lab of Prof. Andrew McMichael at the Weatherall Institute of Molecular Medicine in Oxford. He then moved to Yale University for his postdoctoral training with Prof. Richard Flavell in one of the leading immunology laboratories in the world. As a postdoctoral fellow, Dr. Willinger developed novel experimental models to study the human immune system in vivo (Cell Host Microbe 2010, PNAS 2011, Trends Immunol 2011, Nat Biotechnol 2014). He also identified molecular mechanisms that regulate T lymphocyte homeostasis and migration (PNAS 2012, JEM 2014, PNAS 2015). In 2015, Dr. Willinger joined the Center for Infectious Medicine at Karolinska Institute to continue his research on the human immune system, focusing on immune responses in the gut and lung.
Hana Kammoun, PhD, Postdoctoral Fellow
Hana received her PhD in Biotechnology from Institut Pasteur de Lille (IPL), France for her work on a live attenuated Bordetella pertussis vaccine against respiratory infections. After her PhD she did a short postdoc at the Center for Infection and Immunity Lille (CIIL), France where she gained experience in mycobacterial genetics. Hana has a strong background in lung immunology and microbiology. In her spare time she likes photography and sports.
Natalie Sleiers, Laboratory technician
Natalie has been working at Karolinska Institutet/Karolinska Sjukhuset for several years. She likes to spend her spare time either in the stable or the gym. She also loves to watch movies, another big hobby of her.
Elza Evren, PhD student
Elza received her Master’s Degree in Immunology from University Pierre and Marie Curie, France, in 2016. She did her master’s thesis in Harvard Medical School where she studied poly-N-acetyl-glucosamine, a bacterial capsule polysaccharide that provides a potentially broad-spectrum target for vaccination. She is fond of travelling, exploring new cultures and learning from past stories.
Selected publications (last 5 years)
Dynamin 2-dependent endocytosis sustains T-cell receptor signaling and drives metabolic reprogramming in T lymphocytes.
Proc. Natl. Acad. Sci. U.S.A. 2015 Apr;112(14):4423-8
Development and function of human innate immune cells in a humanized mouse model.
Nat. Biotechnol. 2014 Apr;32(4):364-72
Dynamin 2-dependent endocytosis is required for sustained S1PR1 signaling.
J. Exp. Med. 2014 Apr;211(4):685-700
ESCaping rejection: A step forward for embryonic-stem-cell-based regenerative medicine.
Cell Stem Cell 2014 Jan;14(1):3-4
Human hemato-lymphoid system mice: current use and future potential for medicine.
Annu. Rev. Immunol. 2013 ;31():635-674
Canonical autophagy dependent on the class III phosphoinositide-3 kinase Vps34 is required for naive T-cell homeostasis.
Proc. Natl. Acad. Sci. U.S.A. 2012 May;109(22):8670-5
Improving human hemato-lymphoid-system mice by cytokine knock-in gene replacement.
Trends Immunol. 2011 Jul;32(7):321-7
Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung.
Proc. Natl. Acad. Sci. U.S.A. 2011 Feb;108(6):2390-5
Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo.
Proc. Natl. Acad. Sci. U.S.A. 2011 Feb;108(6):2378-83
A mouse model for the human pathogen Salmonella typhi.
Cell Host Microbe 2010 Oct;8(4):369-76
We are looking for talented and highly motivated students and postdocs to join our new research group. To apply, submit cover letter, CV with publication list, and contact information of three references to the group leader Tim Willinger (email@example.com).