Category: NSI Rising Star Seminar

NSI Rising Star Seminar: Søren E. Degn

In our next NSI Rising Star Seminar, we will be hosting Søren E. Degn (PhD, Associate Professor, DFF Research Leader and Lundbeckfonden Ascending Investigator) with a talk on “B cells – the bad boys at the back of the bus”. Look forward to seeing you there!

Meeting details:
Speaker: Søren E. Degn
Title: B cells – the bad boys at the back of the bus
Time and date: Thursday, February 27 at 14:00
Meeting link: https://uio.zoom.us/j/67297197985?pwd=bqgeirifg4EMy2Tph8fTcgzqlnWauU.1
Meeting ID: 672 9719 7985
Passcode: 916148

Talk abstract:
B cells are increasingly recognized not simply as precursors of antibody-producing cells, but as central players across a broad range of autoimmune diseases. In recent work, my group demonstrated that B cells can act as primary antigen-presenting cells priming proto-autoreactive T cells and driving epitope spreading in a murine model of systemic lupus erythematosus (Fahlquist-Hagert et al., Nature Communications 2023). Taking this as a starting point, I will touch upon recently published (Fahlquist-Hagert et al., iScience 2024) and unpublished work characterizing the role of T-follicular regulatory cells in curbing autoreactive germinal center responses, including the use of an intravital abdominal imaging window approach for longitudinal studies of immune processes in the spleen (https://doi.org/10.1101/2025.01.06.631523). Finally, I will present ongoing work, in which we have identified a previously unappreciated link between age-associated B cells and CD8 T cell activation and exhaustion.

More information about Søren E. Degn:
Søren completed his BSc (2004) and MSc (2007) in Molecular Biology at Aarhus University. During his MSc, he spent a year at the Departments of Biochemistry and Immunology at the University of Toronto, Canada where he worked with Professor David E. Isenman. Søren then joined the laboratory of Professors Jens Chr. Jensenius and Steffen Thiel, where he completed his PhD in Immunology (2010), on the topic of the lectin pathway of complement. His thesis work included the discovery of a novel regulatory component of this pathway, the protein MAp44 (Degn et al., Journal of Immunology 2009). In the course of his PhD studies, Søren also worked for a year in the laboratory of Professor Michael C. Carroll at the Immune Disease Institute, Harvard Medical School, where he contributed to elucidating how influenza viral antigen is transported and presented in the draining lymph node in a vaccination setting (Gonzalez et al., Nature Immunology 2010). Following award of his PhD degree, Søren continued his work on the lectin pathway of complement as a postdoctoral fellow (2011-2013) with Professors Jens Chr. Jensenius and Steffen Thiel. In a series of papers (Degn et al., Journal of Immunology 2012; Degn et al., Journal of Immunology 2013; Degn et al., PNAS 2014), Søren presented a novel theory for the activation mechanism of the lectin pathway of complement. In 2013, he returned to the laboratory of Professor Michael C. Carroll, now at the Program in Cellular and Molecular Medicine (PCMM) at Boston Children’s Hospital and Harvard Medical School. During his Marie Curie Fellowship at the PCMM, Søren elucidated the clonal evolution of autoreactive germinal centers (Degn et al., Cell 2017), and built his expertise within lymphocyte biology using in vivo models and two-photon microscopy, forming the basis of his return to Aarhus University as a Group Leader and Assistant Professor in 2017. In March 2022, he was promoted to tenured Associate Professor at the Department of Biomedicine. Søren continues to work on autoimmune diseases (van der Poel et al., Cell Reports 2019; Juul-Madsen et al., PNAS 2021; Fahlquist-Hagert et al., Nature Communications 2023), but in recent years his attention has also turned to the molecular mechanism behind antigen-driven activation of the B-cell receptor (Ferapontov, Omer et al, Nature Communications 2023; Degn & Tolar, Nat. Rev. Immunol. 2024).
Google scholar: https://scholar.google.com/citations?user=EyXW-8sAAAAJ&hl=en&oi=ao

Key papers: 
1. Antigen presentation by B cells enables epitope spreading across an MHC barrier
2. Antigen footprint governs activation of the B cell receptor

NSI Rising Star Seminar: Anna Hammerich Thysen

In our next NSI Rising Star Seminar, we will be hosting Anna Hammerich Thysen (Assistant Professor, Department of Biotechnology and Biomedicine, Technical University of Denmark) with a talk on “Do dural brain border immune cells mediate brain fog in allergic asthma?”. Look forward to seeing you there!

Meeting details:
https://uio.zoom.us/j/67297197985?pwd=bqgeirifg4EMy2Tph8fTcgzqlnWauU.1
Meeting ID: 672 9719 7985
Passcode: 916148

Title of the talk: Do dural brain border immune cells mediate brain fog in allergic asthma?

Abstract:
The Covid-19 pandemic emphasized the long-lasting neurological symptoms that accompany immune diseases of the lung. Individuals with airway allergy and asthma experience deficits in learning, memory and attention span; a so-called brain fog. For individuals with seasonal allergy, symptoms peak during the season of their allergen, suggesting a direct correlation between allergen dose and neurological response. Here, we address this otherwise overlooked symptom burden. Our hypothesis is that allergy-like immune cells at the dural brain border mediate the cognitive burden in airway allergy and asthma. We are establishing a mouse model for memory and learning deficits in allergic asthma. By combining our mouse model with high-dimensional flow cytometry, immunohistochemistry, single cell analysis, and genetic mouse models, our aim is to 1) map the immunological and neurological mechanisms underlying lung-to-brain cognitive symptoms; and to 2) design and test novel treatment strategies.

Bio:
Dr. Anna Hammerich Thysen is an Assistant Professor at the Department of Biotechnology and Biomedicine at the Technical University of Denmark (DTU). Anna received her PhD degree from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) under the supervision of Susanne Brix. Following collection of 189 immune cell and cytokine parameters in 541 infants; Anna identified discrete immune phenotypes in 18-months-old infants preceding the development of transient and persistent asthma at school age. During her postdoc in the lab of Katharina Lahl, Anna developed a neonatal re-infection model for respiratory syncytial virus in mice. Anna was able to show a critical role for cDC1 dendritic cells during healthy re-infection, and a lack of neonatal cDC1 DCs would lead to massive airway eosinophilia and type 2 immune pathology in adulthood. Anna then ventured into research in industry; first with neuroimmune diseases at Lundbeck and then allergy and asthma at ALK. As a solo mother of three young children, Anna is now in the initial stages of establishing her independent career with a research focus on type 2 immune regulation in the neuroimmune, viral, and neonatal aspects of airway disease.

Google scholar: https://scholar.google.dk/citations?user=8_OS3k4AAAAJ&hl=da

Key publications:

  1. Distinct immune phenotypes in infants developing asthma during childhood. Science translational medicine 12, no. 529 (2020): eaaw0258.
  2. Season of birth shapes neonatal immune function. Journal of Allergy and Clinical Immunology 137, no. 4 (2016): 1238-1246.

NSI Rising Star Seminar: Clarissa Campbell

In our next NSI Rising Star Seminar, we will be hosting Clarissa Campbell (CeMM, Austrian Academy of Sciences) with a talk on “T cell regulation by bacterial metabolites”. Look forward to seeing you there!

Meeting details:
Monday 7th October at 13:00
https://uio.zoom.us/j/62979749183?pwd=l2eOW7eqdaGiBElGJaWYy2VskyWe76.1
Meeting ID: 629 7974 9183
Passcode: 237779

Title of talk: T cell regulation by bacterial metabolites

Abstract:
Intestinal microbial communities expand the functional capabilities of the host via their metabolic attributes. From energy harvest to the production of vitamins, the gut microbiota shapes mammalian physiology and is often considered a postnatally developed “organ”. Yet, the microbiome poses a formidable challenge to the immune system: How can we host trillions of bacteria without mounting an inflammatory response? Gut immune homeostasis relies on the balanced action of suppressive and inflammatory T cell subsets. Using transgenic mouse models, engineered bacteria and gnotobiotic experiments, we discovered that common products of bacterial metabolism including short-chain fatty acids and microbe-derived bile acids affect the differentiation of Foxp3+ immunosuppressive regulatory T (Treg) cells at the steady state. Further, we found that Treg cells induced in response to bacterial cues support the establishment and maintenance of intestinal microbial communities. More recently, we discovered that intestinal inflammation leads to the loss of microbe-derived bile acids, thus contributing to fuel T cell-driven pathologies. Altogether, our work uncovered a prominent role for microbial metabolites in shaping host immunity by modulating T cell responses both at the steady state and during inflammatory settings.

Bio:
Clarissa Campbell studied biology with a minor in genetics at the Federal University of Rio de Janeiro (UFRJ) and subsequently earned a master’s degree from the Oswaldo Cruz Foundation (FIOCRUZ), investigating how bacterial molecules exert immunomodulatory effects on mammalian cells via nuclear receptors, a topic she would continue to explore throughout her career. She joined the Tri-Institutional Immunology and Microbial Pathogenesis Program at Weill Cornell Medical College in New York as a graduate student where she specialized in mucosal immunology and regulatory T (Treg) cell biology. After obtaining her PhD, Clarissa Campbell remained under the mentorship of Dr. Alexander Rudensky at Memorial Sloan Kettering Cancer Center to continue her work on host-commensal interactions and pursue broader scientific questions bridging the fields of immunology and metabolism. Her research has characterized a circuit whereby microbial metabolites including short-chain fatty acids and secondary bile acids facilitate the differentiation of peripherally induced Treg cells, which in turn suppress immune responses to colonization and preserve a niche for a group of intestinal bacteria. More recently, she found that a bile acidsensing nuclear receptor contributes to the cell-intrinsic responsiveness of effector T cells to fasting. Clarissa Campbell joined CeMM as a principal investigator in July 2021. Her lab is interested in investigating how changes in microbial and organismal metabolism contribute to regulating immune-cell function.

Key publications:

  1. Nuclear receptor LXRβ controls fitness and functionality of activated T cells. J Exp Med. 2021
  2. FXR mediates T cell-intrinsic responses to reduced feeding during infection. Proc Natl Acad Sci USA. 2020
  3. Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells. Nature. 2020

NSI Rising Star Seminar: Abigail Vanderheiden

In our next seminar from the NSI Rising Star Seminar series, we will be hosting Abigail Vanderheiden (Washington University in St. Louis, Missouri, USA) with a talk on “ Investigating the contribution of the immune response to memory deficits after COVID-19 in mice”.
Look forward to seeing you there!

Meeting details:
Thursday, 5. September, 15.00
https://uio.zoom.us/j/65066940943?pwd=CX8za4Wa20jZLAib9fHOXQzQzzanRn.1

Abstract: 
Millions of patients with post-acute symptoms of COVID-19 or ‘long-COVID’ are accumulating worldwide, however, the underlying mechanisms driving neurological dysfunction and how vaccination impacts risk are unknown. Current evidence suggests that SARS-CoV-2 does not cause widespread infection of the central nervous system (CNS). Despite this, post-mortem analyses of the hippocampi of COVID-19 patients have identified microglial activation, decreased neurogenesis, blood-brain barrier disruption, and pro-inflammatory cytokine production, including Interleukin-1b (IL-1b) a key component of the innate immune defense against viral infection. Here, we utilize a novel mouse model of the neurological effects of COVID-19 to investigate how innate immunity impacts memory deficits after SARS-CoV-2. We find that intranasal infection of C57BL/6J mice with the beta variant of SARS-CoV-2 (B.1.351) causes post-acute memory deficits as measured via the Novel Object recognition test that correlate with decreases in hippocampal neurogenesis and trisynaptic circuit synapse number. We find that SARS-CoV-2 infection prompts peripheral immune cell infiltration, persistent microglial activation, and elevated levels of IL-1b in the hippocampus. Mechanistically, we demonstrate that IL-1R1 signaling on neural stem cells promotes loss of hippocampal neurogenesis and subsequent memory deficits after SARS-CoV-2. Vaccination with a low dose of adenoviral vectored Spike protein prevents production of IL-1b in the hippocampus and subsequently protects against loss of neurogenesis and memory deficits after breakthrough SARS-CoV-2 infection. Combined, these data identify microglial production of IL-1b as one pathway driving memory deficits after COVID-19 that can be prevented by prior vaccination.

Bio: 
Dr. Vanderheiden is a post-doctoral research scholar in the laboratory of Dr. Michael Diamond at Washington University in St. Louis, Missouri, USA. Dr. Vanderheiden performed her Ph.D. work in Immunology under the mentorship of Dr. Mehul Suthar at Emory University (Atlanta, GA, USA) where she investigated innate immune signaling in response to West Nile virus and SARS-CoV-2 and helped develop a novel mouse model of SARS-CoV-2 infection. She began her post-doctoral training under Dr. Robyn Klein at Washington University in St. Louis, where she used this mouse model to investigate how IL-1 signaling promotes memory deficits after COVID-19. In 2023, Dr. Klein left Washington University and Dr. Vanderheiden moved to the lab of Dr. Michael S. Diamond do continue her post-doctoral studies on how the immune response to SARS-CoV-2 infection impacts post-acute neurological dysfunction after COVID-19.

Key publications:
1. “Vaccination reduces central nervous system IL-1β and memory deficits after COVID-19 in mice.” Nature Immunology (2024): 1-14.
2. “COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis.” Brain 145.12 (2022): 4193-4201.
3. “Type I and type III interferons restrict SARS-CoV-2 infection of human airway epithelial cultures.” Journal of virology 94.19 (2020): 10-1128.

NSI Rising Star Seminar: Camilla Engblom

In our next seminar from the NSI Rising Star Seminar series, we will be hosting Camilla Engblom (Karolinska Institutet, Stockholm, Sweden) with a talk on “Mapping B and T cell receptors in tissues using spatial transcriptomics”.
Look forward to seeing you there!

Meeting details:
Thursday, 15. august, 13.00
https://uib.zoom.us/j/64667274238?pwd=aNkElnisAOMYP9WaMaVbaGb5lXtG0L.1
Meeting ID: 646 6727 4238
Password: guf3QPtA

Abstract: 
B and T cells perform functions critical to human health and they develop, differentiate, and expand in spatially distinct sites across the body. Both B and T cells express clonal heritable antigen receptors that confer exquisite molecular (i.e., antigen) specificity. Antigen receptors can be defined by sequencing, but these methods require tissue dissociation, which loses the anatomical location, and the surrounding functionally relevant environmental cues. Linking specific clonal sequences to their molecular and cellular surroundings, i.e., ‘clonal niche’, could help us understand and harness B and T cell activity. A technological bottleneck has been to capture the location of antigen receptor sequences, and by extension B and T cell clonal responses, directly within tissues. To address this, we recently developed a spatial transcriptomics-based approach (Spatial VDJ) and associated computational pipelines to reconstruct B and T cell clonality in human tissues. Using this technology, we spatially resolve B and T cell receptors within immune and tumor tissues, as well as B cell clonal evolution within germinal centers. Combined, Spatial VDJ links B and T cell clonal responses to their microenvironment with applications to various immune-related pathologies, including infections, cancer and autoimmune diseases. 

Bio: 
Dr. Camilla Engblom is a SciLifeLab Fellow and a recently appointed Assistant Professor in the Division of Immunology and Allergy and the Department of Medicine, Solna at the Karolinska Institutet (KI). She received her PhD in Immunology from Harvard University in 2017 focusing on long-range cancer-host interactions involving myeloid cells (Mikael Pittet’s lab at Massachusetts General Hospital/Harvard Medical School). As a MSCA postdoctoral fellow in Jonas Frisén’s lab (KI) in a collaboration with Joakim Lundeberg’s lab, Dr. Engblom developed a spatial transcriptomics-based tool (Spatial VDJ) to map B cell and T cell receptors within human tissues. Located at SciLifeLab and the Center for Molecular Medicine (KI), the Engblom lab’s main research focus is to spatially and functionally resolve B cell clonal dynamics during cancer.

Key publications:

  1. C. Engblom*/K. Thrane*/Q. Lin*, et al. Science. (2023).
  2. Zilionis R*, Engblom C*, Pfirschke C*, Savova V*, et al. Immunity. 2019. May 21;50(5):1317-1334.
  3. Engblom C*, Pfirschke C, et al. Science. 2017 Dec 1;358(6367).
  4. Pfirschke C*, Engblom C*, et al. Immunity. 2016 Feb 16;44(2):343-54.