Gertrud Malene Hjortø
Molecular and Translational Pharmacology
2200 København N
The focus of the Hjortø group is to gain a detailed molecular understanding of the systems that regulate immune cell activity and positioning in the body, with a special focus on the chemokine receptor CCR7 and its three natural ligands CCL19, CCL21 and CCL21Tailless. CCR7 and its ligands orchestrate a central immune hub through controlled recruitment of dendritic cells (DCs) and various T cell subsets to the lymph nodes (LN) for following T cell activation. Thus CCR7 effectively controls the onset of various immune responses. The overall aim of our research is to apply our newfound knowledge on the molecular regulation of CCR7 and other central chemokine receptors to modulate immune cell behavior in vivo through external delivery of allosteric modulators discovered by us. Our overall goal is to drive a discovery process towards new drugs that may be used for treatment of cancer, chronic inflammation or other relevant diseases.
To obtain this goal, we apply classical pharmacological methods to assess changes in chemokine receptor activation upon stimulation and study the effect of such changes on primary immune cell behavior. This pharmacological analysis includes measurements of receptor-mediated changes in intracellular signaling, beta-arrestin recruitment and internalization as well as intricate analysis of primary immune cell activation and migration state. We are experts in tracking of human immune cell migration using time-lapse microscopy. From this we can report changes in chemotactic index, migration speed etc. of cells responding to linear gradients of chemotactic signals in the absence or presence of agents that affect e.g. receptor ligand interaction or downstream signaling events.
The Hjortø group has published several papers on the role of CCR7 in controlling human DC signaling and migration and differences between the three natural ligands of CCR7 in their receptor activation mode. Chemokine receptors are decorated by posttranslational modifications (PTMs) that are often seen to be important for correct chemokine presentation and receptor activation. We recently discovered that such modifications can be targeted with externally added peptides to promote better ligand-receptor interaction, to elicit more potent chemokine responses. Our patent application (Chemotaxis potentiating peptides and uses thereof) aims at exploiting such peptides to manipulate the interaction between CCL21 and its receptor CCR7.
Jørgensen, A. S., Brandum, E.P., Mikkelsen, J.M., Orfin, K.A., Boilesen, D.R., Egerod, K.L., Moussouras, N.A., Vilhardt ,F., Kalinski, P., Basse, P., Chen, Y., Yang, Z., Dwinell, M.B, Volkman, B.F., Veldkamp, C.T., Holst, P.J., Lahl, K., Goth, C.K., Rosenkilde, M.M., Hjortø, G.M. 2021. The C-terminal peptide of CCL21 drastically augments CCL21 activity through the dendritic cell lymph node homing receptor CCR7 by interaction with the receptor N-terminus. Cell Mol Life Sci. 78:6963-6978. IF 9.261
Brandum, E. P., Jorgensen, A. S., Rosenkilde, M. M. & Hjorto, G. M. (2021). Dendritic Cells and CCR7 Expression: An Important Factor for Autoimmune Diseases, Chronic Inflammation, and Cancer. Int J Mol Sci 22(15):8340, doi:10.3390/ijms22158340. 2020 IF 5.923
Jorgensen, A. S., Adogamhe, P. E., Laufer, J. M., Legler, D. F., Veldkamp, C. T., Rosenkilde, M. M., and Hjorto, G. M. 2018. CCL19 with CCL21-tail displays enhanced glycosaminoglycan binding with retained chemotactic potency in dendritic cells. J. Leukoc. Biol. 104:401-411. IF 4.02
Hjorto, G. M., Larsen, O., Steen, A., Daugvilaite, V., Berg, C., Fares, S., Hansen, M., Ali, S., and Rosenkilde, M. M. 2016. Differential CCR7 Targeting in Dendritic Cells by Three Naturally Occurring CC-Chemokines. Front Immunol. 7:568. IF 3.03
Hansen, M., Met, O., Larsen, N. B., Rosenkilde, M. M., Andersen, M. H., Svane, I. M., and Hjorto, G. M. 2016. Autocrine CCL19 blocks dendritic cell migration toward weak gradients of CCL21. Cytotherapy. 18:1187-1196. IF 3.54
Hansen, M., Hjorto, G. M., Donia, M., Met, O., Larsen, N. B., Andersen, M. H., thor, S. P., and Svane, I. M. 2013. Comparison of clinical grade type 1 polarized and standard matured dendritic cells for cancer immunotherapy. Vaccine 31:639-646. IF 3.918
Undervisnings- og vejledningsområder
2014-present, General priniples of Chemotherapeutics and Molecular Pharmacology B. Sc. Medicine.
2015-present, Cancer chemotherapy/Cancer chemotherapy & immunomodulation M.Sc. Medicine.
2019-present, Basal Human Biology B. Sc. Medicine.
2015-present, General principles of chemotherapeutics B. Sc. Odontology.
2015-present, Cancer chemotherapy M.Sc. Odontology.
2015-present, Basal pharmacology M.Sc. Human Biology.
Covers both lectures and classroom teaching.
PhD.: Immune boosting peptides for improved immune cell activation (running). (UCPH).
M.Sc.: The Immunomodulatory Properties of C21-TP and Biased Signaling at CCR7. (UCPH).
M.Sc.: New GPR183 biased agonist in B-cell activation. (UCPH).
B.Sc.: Chemokine derived peptides in signaling. (UCPH).
M.Sc.: Manipulation of CCR7, a GPCR driving DC and T cell lymph node homing. (UCPH).
M.Sc.: US28 and CX3CR1 induced cell migration. (DTU).
B.Sc.: Mathematical analysis and modeling of DC migration. (DTU).
B.Sc.: Comparative study on migration behavior of DCs matured using different maturation strategies inside complex microstructured polymer scaffolds. (DTU).
PhD.: Microshaping hydrogels and their chemistry in 3D for optimizing/validating DC migration. (DTU).
Conferences and talks Poster and talk, Gordon Research Conference; Chemotactic Cytokines, Positioning Cells in Immunity and Disease, 2014. Poster and talk, European Cell Migration Conference (ECMC) 2017. Poster and talk, ECMC 2019.