The Immuno-endocrinology lab is looking for colleagues

We are looking for highly motivated master's students to work with us.


Molecular mechanisms underlying pancreatic islet cell failure in Type 1 and Type 2 diabetes

Vacant positionsThe overall aim of the current research portfolio of the Immuno-endocrinology lab is to identify novel therapeutic targets in the pathways leading to pancreatic beta-cell failure with a focus on pancreatic islet beta-cell responses to immune, inflammatory, metabolic and oxidative stress.

Our translational experimental strategy is to move from insulin-producing cell-lines to primary intact or dispersed islets to human islet experiments, the latter mainly used to confirm critical observations from cell lines and rodent islets. Studies also involve animal and clinical studies.

The projects involve PhD, Master’s, Bachelor’s and ERASMUS students with a close and direct supervision and coaching from tenured faculty members. They encourage independence from the start and the opportunity to learn about the diverse aspects of science: literature search, experimental design, experimental planning and execution, data-analysis and -presentation, 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.

Students will have the opportunity to learn following techniques: islet isolation, cell- and islet-culture, viability and functional assays, gene expression (RT-qPCR), protein analysis (reducing and non-reducing SDS-PAGE, Western blotting, immunoprecipitation, protein expression systems, mass spectrometry, size-exclusion chromatography), gene knock –down or- out (siRNA, shRNA, CRISPR-Cas9), plasmid design, cloning, transfection, pancreatic islet handling and usage and many more, depending on the project needs.

The project outline for the ongoing five research lines are described briefly in the following.

1) Molecular switches of the ER stress response in pancreatic beta-cells
Funded by the Danish Diabetes Academy, the Augustinus Foundation, the Møller Foundation and University of Copenhagen

The pathogenesis of type 2 diabetes (T2D) involves beta-cell impairment and death via toxic effects of non-esterified free fatty acids and glucose (glucolipotoxicity, GLT). GLT-induced beta-cell apoptosis is mediated by histone deacetylases, and inhibition of histone deacetylase 3 (HDAC3) prevents GLT-induced apoptosis by reducing ER stress. We wish to investigate the precise targets of HDAC3 in the ER pathway, with the perspective to utilize these in the development of novel antidiabetic drugs. Based on mRNA microarray and acetylomics in INS-1 cells we have identified two strong candidate targets that we wish to validate further in human islets, including expressional profiling, characterization of interaction partners and inhibition using small-molecule inhibitors.

For further information, please contact: Professor Thomas Mandrup-Poulsen, Panum building 12.6.22,

2) The role of circadian clock perturbation in inflammatory β-cell damage
Funded by the University of Copenhagen, the Novo Nordisk Foundation and Independent Research Fund Denmark

Prolonged perturbation of the circadian clock is associated with detrimental metabolic outcomes and risk factors for obesity and diabetes. There is increasing interest in understanding the mutual interplay between the circadian clock and inflammatory responses. Since the pathogenesis of β-cell failure and death in both Type 1 (T1D) and Type 2 diabetes (T2D) involves inflammatory mechanisms the hypothesis of this project is that inflammatory conditions perturb the islet circadian clock, and that clock perturbation sensitizes islets to inflammatory damage. We have recently discovered that inflammatory cytokines lead to aberrant regulation of key clock components in INS-1 cells, and we now wish to confirm and extend these observations in human islets, as well as disentangle the molecular mechanisms.

For further information, please contact: Professor Thomas Mandrup-Poulsen, Panum building 12.6.22,

3) Description of the early steps in proinsulin folding (production) and the consequences for insulin-related diseases (diabetes, hyperinsulinemia).
Funded by Independent Research Fund Denmark and Augustinus Foundation

We are the first group to describe the requirement for proinsulin chaperone (Diabetes, 2019), and building on this discovery we now focus our research efforts on the very early steps in insulin biosynthesis, filling the gaps in our knowledge, with the hope to discover targets for better therapeutic approaches for diabetes and hyperinsulinemia. The project is carried out in collaboration with Uppsala University, Sweden, University of Michigan Medical School, USA, and three other groups from UCPH.

For further information, please contact: Associate Professor Michal Marzec, Panum building 12.6.08,

4) The role of protein folding and degradation in the induction of type 1 diabetes
Funded by the EFSD (July 2017-June 2019), Vissing Foundation, Bjarne Jensen Foundation and Poul og Erna Sehested Hansens Foundation

This project will address a central question in T1D pathogenesis: How does endogenous pancreatic β-cell proteins become immunogenic and initiate β-cell-directed immune attack? We hypothesize that changes in proinsulin folding may trigger beta-cell autoimmunity by generating neo-antigens and wish to test this hypothesis in a variety of biological models.

For further information, please contact: Associate Professor Michal Marzec, Panum building 12.6.08,

5) Targeting mitophagy to prevent beta cell failure in T1D
Funded by the Juvenile Diabetes Research Foundation USA, with the University of Michigan Medical School

T1D results from autoimmune-mediated β-cell damage leading to insufficient functional β-cell mass to meet peripheral insulin demands. β-cells rely upon mitochondrial respiration to generate the energy necessary for insulin synthesis, processing, and secretion. Immune-mediated cytokine release also leads to generation of intracellular reactive oxygen species and mitochondrial damage, which ultimately result in β-cell apoptosis. Indeed, defects in mitochondrial structure and function have been reported in the β-cells of patients with both T1D and T2D. Defects in mitochondrial structure and function are characteristic of impairments in mitophagy, a selective form of mitophagy necessary for elimination of dysfunctional mitochondria; however, the role of mitophagy in T1D pathogenesis is not well understood. Our collaborators at the University of Michigan (PI Scott Soleimanpour) previously discovered a key role for the T1D susceptibility gene Clec16a in control of glucose homeostasis in humans and mice through its regulation of β-cell mitophagy. Therefore, our goal is to dissect the mechanistic and physiologic regulation of Clec16a-mediated mitophagy in β-cells to elucidate its contribution to T1D pathogenesis.

For further information, please contact: Professor Thomas Mandrup-Poulsen, Panum building 12.6.22,