Mandrup-Poulsen Group - Immuno-endocrinology
Despite improved therapies and self-management, Type 1 and type 2 diabetes are still disorders associated with significant over-morbidity, mortality and loss of life quality.
Current treatments are largely symptomatic, and there is an imminent need for better causative treatments based on detailed insights into the molecular and cellular pathogenetic mechanisms.
In our group, we aim to decipher such mechanisms, primarily focusing on circadian, inflammatory, metabolic, and ageing-related pathogenic pathways with the perspective to identify novel therapeutic targets to improve treatment of these diseases and their cardiovascular complications.
The Immuno-endocrinology lab employs an interdisciplinary and collaborative research strategy to unravel transcriptional, translational and posttranslational responses to stress by two complementary approaches: a hypothesis-driven approach evolving from new discoveries in the lab, and an unbiased screening approach employing systems biology and using functional genomics, transcriptomics, proteomics, secretomics and post-translatomics.
Our experimental tactics utilise systems biology, bioinformatics, and in silico modelling, cell-free and cell-based in vitro models, ex vivo and in vivo studies in induced and genetic experimental animals, as well as epidemiological analyses and biomarker studies.
We employ amongst others the following laboratory techniques:
- circadian clock reporter assays
- islet isolation, culture, insulin secretion assays incl. perifusion
- culture of beta-cell, hepatocyte and cardiomyocyte cell-lines,
- viability, apoptosis and functional assays,
- gene expression (RT-qPCR and RNA seq),
- protein analysis (reducing and non-reducing SDS-PAGE, Western blotting, immunoprecipitation),
- gene knock-down or knock-out (siRNA, shRNA, CRISPR-Cas9),
- plasmid design,
- cloning, transfection,
- transgenic animal models,
- and many more, depending on the needs of the project
Metabolic regulation of the circadian clock: roles in the pathogenesis of diabetes and its cardiovascular complications.
Staff
Rasmus Henrik Reeh, MD, PhD student, Lærke Poulsen Larsen, Master’s student, Ludvig Simon Taul, Bachelor’s student and Sussi Mørkeberg Kristoffersen, lab technician
Collaborators
Charna Dibner, University of Geneva, Switzerland; Frank Scheer, Brigham and Womens Hospital, Harvard Medical School, Boston, MA, USA; Dan Levine, University of Pennsylvania, Philadelphia, PA; USA, Louis Ptacek, University of California, San Francisco, CA, USA; Anne Helene Garde, NFA, Copenhagen; Christina Ellervik, Childrens’ Hospital, Harvard Medical School, Boston, MA, USA; Willem Staels, Vrije Universiteit Brussels, Brussels, Belgium; Anke Fender, University of Essen, Essen, Germany.
Prolonged perturbation of the circadian clock is associated with detrimental metabolic outcomes and a risk factor for obesity and cardiometabolic diseases. There is increasing interest in understanding the mutual interplay between the circadian clock and metabolic/inflammatory responses.
The hypothesis of these projects is that metabolic and inflammatory stressors perturb the circadian clock in key metabolic organs, and that clock perturbation sensitizes these cells to damage.
We have recently discovered that high glucose and/or free fatty acid concentrations and inflammatory cytokines lead to distinct aberrant regulations of key clock components in insulin-producing cell lines, and we now wish to confirm and extend these observations in other model systems, as well as disentangle the molecular mechanisms.
The Immuno-endocrinology lab is supported by grants from a number of private and public foundations. Listed below is a selection of public and private funds the group has received in the last years
Independent Research Fund Denmark
Læge Sofus Carl Emil Friis og hustru Olga Doris Friis Legat.
Research education
The Immuno-endocrinology lab prioritises research-based teaching by taking responsibility for pre- and postgraduate courses, as well as practical research training of our Bachelor’s, Master’s and PhD students, as well as Postdocs and Visiting Scientists.
Training in our lab
Aside from practical training in the lab, all lab members are encouraged to participate in fundraising, manuscript writing, scientific reviews, academic assessments, research administration and intra- and extra-mural committee work and to contribute actively and positively to group, section, department, faculty and university activities.
The dissemination policy of the Immuno-endocrinology lab
The Immuno-endocrinology lab is careful to secure intellectual property rights via patenting and priority publication in high-rank international periodicals.
Furthermore, we are passionate about data sharing via public databases and dissemination of research findings to the broader public by press releases, presentations at scientific and public meetings, in patient organisations and in the media.
We are looking for highly motivated Master's and Bachelor’s students to work with us, although availability may vary over time. Please take contact well in-time, since we are often booked by students 6-12 mo in advance of the starting date. Additionally, pilot or new projects not listed above may be available at times.
The overall aim
The overall aim of the current research portfolio of the Immuno-endocrinology lab is to identify novel therapeutic targets in the pathways leading to diabetes and its complications with a current focus circadian clock responses to immune, inflammatory, metabolic, ageing- related and oxidative stressors.
Translational experimental strategy
Our translational experimental strategy is to move from cell-lines to primary to human tissue experiments, the latter mainly used to confirm critical observations from cell lines and rodent tissues. Studies also involve animal, clinical and epidemiological studies.
The projects
The projects involve PhD, Master’s, Bachelor’s and ERASMUS students with a close and direct supervision and coaching from other students and tenured faculty members.
Students are encouraged to independence from the start and to learn about the diverse aspects of science: literature search, experimental design, experimental planning and execution, data-analysis and -presentation, use of bioinformatics and AI-tools, interaction with our collaborators as well as grant-writing and active participation in administrative and social aspects of faculty, laboratory and group life.
PhD students are involved in undergraduate teaching and offered mentoring of Bachelor’s or Master’s students in their senior years.
Group members
| Name | Title | Phone | |
|---|---|---|---|
| Lærke Poulsen Larsen | Master Student | ||
| Rasmus Henrik Reeh | Research Assistant | +4535333848 | |
| Sussi Mørkeberg Kristoffersen | Laboratory Technician | ||
| Thomas Mandrup-Poulsen | Professor | +4535327254 |
Group Leader
Thomas Mandrup-Poulsen
Professor
Phone: +45 3033 0387
tmpo@sund.ku.dk
ORCID: 0000-0002-3215-9273