disputerer for ph.d.-graden i helsevitenskap og vil offentlig forsvare avhandlingen:
“The role of interleukin-1 receptor antagonist in normal and malignant hematopoiesis”
Prøveforelesning over oppgitt emne holdes 10.15 i Auditorium Cortex:
Disputasen starter kl. 1215 i Auditorium Cortex.
Populærvitenskapelig sammendrag av avhandlingen:
Inflammation is associated with blood cancer. High levels of the inflammatory mediator interleukin-1β (IL-1β) deregulates blood differentiation and contributes to the development and progression of blood cancer. However, little is known about its natural repressor, IL-1 receptor antagonist (IL-1RN), in both health and disease.
Here, we found that low IL-1RN is associated with poor prognosis in patients of an aggressive type of blood cancer that can be fatal within weeks if not treated, acute myeloid leukemia. In immunodeficient mice transplanted with human blood cells from patients, treatment with IL-1RN reduced the expansion of blood cancer cells.
Genetic deletion of IL-1rn in mice led to unbalanced blood stem cell and progenitor subsets and their biased differentiation, by overactivation of IL-1β pathway at least in part through the transcription factor NF-κB. Low IL-1rn was observed in an experimental mouse model of blood cancer, and genetic deletion of IL-1rn from either blood cells or neighbouring regulatory cells in the bone marrow accelerated disease progression. In turn, treatment with IL-1RN protects against disease.
Our data reveal that blood cell differentiation is controlled by balanced IL-1β/IL-1RN levels under physiological conditions, and that loss of IL-1RN results in enhanced stimulation of IL-1β that may contribute to blood cancer development and progression. We further provide a new rationale for IL-1β blockade therapeutic potential in AML and a new means through administration of IL-1RN.
Group Leader Lorena Arranz, PhD, Stem Cells, Ageing And Cancer Research Group, Institutt for Medisinsk Biologi, Det Helsevitenskapelige Fakultet, UiT Norges Arktiske Universitet.
Senior Research Fellow Paloma García, PhD, University of Birmingham.
Assistant Professor Cesar Nombela-Arrieta, PhD, University and University Hospital Zürich - 1. opponent.
Group Leader Judith Staerk, PhD, Center for Molecular Medicine Norway - 2. opponent.
Professor Eva Sjøttem, PhD, Institutt for Medisinsk Biologi, Det Helsevitenskapelige Fakultet, UiT Norges Arktiske Universitet – leder av komité.
Professor Emeritus Jan-Olof Winberg, Institutt for medisinsk biologi, Det Helsevitenskapelige Fakultet, UiT Norges Arktiske Universitet.