ENDomics Lab
Endothelial Research Group
University Medical Center Hamburg-Eppendorf Department of Oncology, Haematology and Bone Marrow Transplantation
Campus Forschung (N27), Ground Floor, Rm 00.074/ 00.075/ 00.061
Martinistr. 52
20246 Hamburg
Telephone:
+49 40 7410-59719 (Lab)
+49 40 7410-58798 (Office Dr. Körbelin)
Telefax:
+49 40 7410-57187 (Lab)
+49 40 7410-40084 (Office)
Website (external):
Core Team Members:
Dr. rer. nat. Jakob Körbelin (PI)
Maria Stamataki, M.Sc. (Ph.D. Student)
Merrit Rothe, M.Sc. (Ph.D. Student)
Julia Lüschow, M.S.c (BTA)
Julie Ann Mendoza (BTA, Lab Manager)
Zexin Cao, Master of Surgery (Med. Doktorand)
Overview
Endothelial dysfunction is hallmark of vascular diseases and cancer. We, therefore, apply an integrative multi-omics approach supplemented by in silico-based bioinformatics and functional cell biology to decipher the pathological molecular signatures of endothelial cells in different vascular diseases and lung cancer. By developing organo-specific AAV vectors specifically-targeting endothelial cells we are able to study the molecular basis of endothelial dysfunction and evaluate the potential of new endothelium-based pharmacological and gene therapies.
Mission and Background
The vasculature is an essential part of the human body and provides every single cell in each organ with nutrients and oxygen. The blood vessels of one single person stretch over a total length of 100,000 km, which equals the distance of 2.5 times around the globe. Capillaries, consisting of only one layer of endothelial cells are the smallest vessels in the body and account for 80% of the total vessel length. Endothelial cells play a pivotal role in regulating the integrity of the whole vascular system. A healthy and intact vasculature in turn, is essential for keeping up the body’s fine-tuned homeostasis. It is not surprising that a vast number of diseases is linked to endothelial dysfunction. We believe that endothelial cells are the key to treating a broad range of diseases, especially those affecting the well-perfused large organs such as lung and brain. Moreover, malignant diseases may be treated by targeting endothelial cells, as tumor development and metastasis are heavily influenced by the tumor vasculature. Our team is working on the development of novel endothelial-based gene therapy strategies for a broad range of diseases linked to vascular dysfunction. As part of the ENDomics lab, we are most strongly interested in (but not limited to) pulmonary diseases with a focus on pulmonary (arterial) hypertension.
Technology
Viral vectors based on the adeno-associated virus (AAV) are a very promising tool to deliver therapeutic genes to human cells. Different AAV vectors have successfully been used in preclinical and clinical gene therapy trials for a broad range of diseases and some of them have even been approved for commercial gene therapy in the USA and the EU. Unfortunately, most available AAV vectors lack efficient tropism for endothelial cells. To redirect AAV to new, formerly inaccessible targets (i.e., endothelial cells) we employ random peptide libraries displayed on the AAV capsid. Our AAV display peptide libraries, which have initially been developed in Martin Trepel’s Receptor Targeting Lab, consist of up to 100 million different peptide-presenting capsid variants. By employing in vivo screening approaches over multiple selection rounds on the target cells of choice, we have been able to isolate endothelial-directed AAV vectors for different organs, such as AAV-BR1 (brain ECs) and AAV2-ESGHGYF (pulmonary ECs). Employing these vectors, we are able to assess novel gene therapy approaches for vascular diseases in preclinical settings. In addition, by constantly improving our screening approaches (in vitro, in vivo, ex vivo and combinations thereof) and by constantly improving our random AAV display peptide libraries, we aim to further increase vector efficacy and expand our portfolio of targeted AAV vectors to different organs and species.
Publications:
Find our lab member's complete list of publications at
Pubmed
.
Interested in joining us?
We are constantly looking for highly motivated medical or master’s students.
Feel free to contact us by email
Dr. Jakob Körbekin ( j.koerbelin@uke.de )