Lecture Archive

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Karolinska Research Lectures – John O’shea

Karolinska Research Lectures at NOBEL FORUM

October 15, 16.30

John O’Shea

National Institutes of Arthritis and Musculoskeletal and Skin Diseases, Scientific Director, National Institute of Health, Bethesda, USA

http://irp.nih.gov/pi/john-oshea

Title: Basic and Applied Cytokine Signaling: From Jakinibs to Super-enhancers

Cytokines are critical for all phases of immune responses, with key functions ranging from supporting hematopoiesis to promoting differentiation of immune cells. In addition to their role in host defense and immunoregulation, cytokines are major contributors to the pathophysiology of immune-mediated disease. Understanding the molecular basis of action therefore represents a fascinating basic problem in cell signaling that yields clinically relevant insights. A large subset of cytokines exerts its effects through Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway.  Our findings that JAK3 mutations underlie autosomal recessive severe combined immunodeficiency led us to propose that JAK inhibitors would represent a new class of immunomodulatory drugs, which resulted in two patents.  At present, there are three FDA-approved JAK inhibitors and many others in late-phase clinical trials including ongoing trials at the NIH.

Deciphering precisely how external and intrinsic signals combine to regulate cell behavior remains a challenge.  We have found that cytokines acting via STATs have a major impact on the enhancer landscape of differentiating helper T cells, an important class that includes “superenhancers.”   A major goal of the lab at present is to understand how intrinsic lineage-defining transcription factors work in concert with signal-dependent transcription factors like STATs to alter the epigenomes of immune cells and how this relates to genetic associations with autoimmune disease and drug action.

Host: Ronald van Vollenhoven, Karolinska Institutet

Ronald.van.Vollenhoven@ki.se

Contact: Tatiana Goriatcheva, Nobel Office, Nobel Forum,

tel. 524 87805, tatiana.goriatcheva@nobel.se

Information

The Nobel Prize in Physiology or Medicine will be announced Monday October 5 at 11.30 at earliest, Nobel Forum, Nobels väg 1, 171 77 Stockholm.

Registration and press id is required to attend the Press Conference.

Registration:
When  the  Secretary General begins his announcement at the Press Conference, the following information material will become available at www.nobelprizemedicine.org and at www.nobelprize.org:

  • Open webcast from the Press Conference
    • Press releases in English and Swedish
    • Scientific background in English
    • Illustrations, web links and further reading

At the venue several experts will be available for interviews in Swedish or English (5-10 minutes), please indicate in the registration.

Register for press accreditation HERE

Karolinska Research Lectures – Vijay K. Kuchroo

Karolinska Research Lectures at NOBEL FORUM

September 17, 16.30

Vijay K. Kuchroo

Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.

http://kuchroo-lab.bwh.harvard.edu/

Title: Single-cell genomics identifies novel regulators of metabolic andfunctional states of Th17 cells

Recently a subset of interleukin (IL)-17-producing T cells (TH17) distinct from TH1 or TH2 cells was described and shown to have a crucial role in the induction of autoimmune tissue injury. In contrast to the effector T cells, CD4+CD25+, Fox-P3+ regulatory T cells (T-regs) inhibit autoimmunity and protect against tissue inflammation.  TGF- is a critical differentiation factor for the generation of T-regs and using Foxp3-GFP “knock-in” mice we have shown that IL-6, an acute phase protein induced during infection, inflammation and injury inhibits the generation of Foxp3+ T-reg cells and induces proinflammatory Th17 cells (Bettelli et al., 2006). Our data therefore suggests a reciprocal relationship in the generation of pathogenic (Th17) T cells that induce autoimmunity and regulatory (Foxp3+) T cells that inhibit autoimmune tissue injury. Accumulating data suggests that there are three distinct steps in Th17 differentiation: Induction, Amplification and Stabilization mediated by distinct cytokines and loss of any of the cytokines (TGF-b, IL-6, IL-21 or IL-23) in the pathway results in a defect in generation of Th17 (Korn et al., 2009). However not all Th17 cells are pathogenic and induce autoimmunity, IL-23 is a key cytokine that induces pathogenicity in Th17 cells (Lee et al., 2012).  Using expression profiling at very high temporal resolution, novel computational algorithms and innovative nano-wire based “knock-down” approaches, we have developed a regulatory network that governs the development of Th17 cells.  The Th17 transcriptional network consists of two self-enforcing but mutually antagonistic modules, which are essential for maintaining a balance between Th17 and other CD4 T cell subsets including Tregs (Yosef et al. 2013, Wu et al., 2013).

In addition to high-density temporal microarray analysis, we have performed single-cell RNA-seq of Th17 cells in order to characterize cellular heterogeneity, identify subpopulations, functional states and learn how gene expression variation affects Th17 effector functions. We have identified novel regulators of Th17 cells both in vivo and in vitro that do not affect Th17 differentiation but affect pathogenic vs. non-pathogenic functional states of Th17 cells.

Host: Marie Wahren, Karolinska Institutet

Marie.Wahren@ki.se

Contact: Tatiana Goriatcheva, Nobel Office, Nobel Forum,

tel. 524 87805, tatiana.goriatcheva@nobel.se

Nobel Minisymposium No. 52

Nobel Minisymposium No. 52 in the series Frontiers in Medicine,  Epigenetics in Health and Disease , April 23rd  2015, Nobel Forum at Karolinska Institutet, Stockholm

 Epigenetics is increasingly recognized as a fundamentally important area of medical research, and is currently a rapidly evolving field.  This Frontiers in Medicine Nobel Minisymposium brings together key opinion leaders in the field to provide insight into our understanding of epigenetics in the context of health and disease. The meeting will provide an opportunity for interaction across different disease and interest areas, and provide a state-of –the art update on recent developments in the field.

Organising committee

Anna Krook, Juleen Zierath, Karl Ekwall, Tomas Ekström, Juha Kere and  Anna Wedell

For further information please contact barbro.svensson@ki.se

 

Program_Nobel Symposium_April23 2015