Welcome to the lab.
Our lab studies the roles of platelets beyond hemostasis, especially their interactions with cells of the innate immune system (macrophages and neutrophils) during inflammation of the liver, kidney and intestine.
Platelets are small, anucleate cells that patrol the vasculature to immediately respond to vessel breaches and restore hemostasis. In recent years there has been accumulating evidence that platelets also interact with and regulate cells of the (innate) immune system. It is now accepted that they play roles beyond hemostasis and contribute to (thrombo-)inflammatory processes in disease.
Previously, using intravital microscopy of the mouse liver, we visualized platelet interactions with Kupffer cells and showed that these platelet-macrophage interactions (i) are critical for clearing aged platelets from the circulation and (ii) facilitate platelets to sense the activation status of Kupffer cells through the platelet receptor GPIb.
We are currently employing intravital microscopy, tissue clearing, primary cell culture and other state-of-the-art techniques to understand the complex interplay between platelets and the innate immune system in the liver, kidney and intestine under (patho)physiologic conditions. We are also studying the mechanisms through which platelet clearance in health and disease feeds back to platelet production by megakaryocytes in the bone marrow.
Our latest paper about how Tacrolimus affects Kupffer cells‘ capability to fight infections just got published online at Hepatology.
Immunosuppressants like Tacrolimus (which belongs to the family of NFAT inhibitors) are used to prevent organ rejection after transplantation. While we know a lot about how Tacrolimus affects lymphocytes (especially T cells), we don’t know much about their impact on innate immunity, e.g. on macrophages. We know, however that liver macrophages (Kupffer cells) are especially important for fighting bloodstream infections. Data from >2,700 liver transplant recipients showed that tacrolimus increased the likelihood of infection.
Using a mouse model of acute bacteremia, we found that most bacteria were sequestered in the liver. Bacteria were more likely to disseminate and kill the host in tacrolimus‐treated mice. Using intravital imaging we identified the mechanisms underlying this observation.
Reduced capability of Kupffer cells to capture, phagocytose and destroy bacteria in tacrolimus‐treated animals. In addition, a gene expression analysis of infected Kupffer cells showed that the TREM‐1 pathway was significantly downregulated after tacrolimus treatmemt. In summary, we found that tacrolimus treatment has a direct impact on Kupffer cells thereby compromising their capacity to fend off infections
Check it out here: https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.31499
Carsten gives a talk at the Blood and Bone online seminar series (https://bloodandboneseminar.com/) about Studying platelet clearance using intravital microscopy.
Work with us
We are looking for motivated students from all fields of the life sciences (Biochemistry, Biology, Chemistry or Medicine) that are interested in studying the interactions between platelets and the innate immune systeme in health and disease. If you are interested in doing your Bachelor, Master, PhD or MD thesis in our lab, please send your CV with a short cover letter to firstname.lastname@example.org