Vascular Biology Group
Over one billion people worldwide are affected by high blood pressure (hypertension). Hypertension is a major risk factor in many diseases including heart failure, stroke, chronic kidney disease, erectile dysfunction and Alzheimer's disease. Importantly, 90% of the people with hypertension are genetically prone to developing high blood pressure, but relatively little is known about the mechanisms that underlie this susceptibility.
In the Vascular Biology Group we investigate blood vessels. We are interested in the cells that control the diameter of arteries, namely smooth muscle cells, which can contract and relax. In hypertension and atherosclerosis, hyper-contractility and restructuring of arterial smooth muscle cells leads to increased arterial tone and/or reduced blood flow. In the smooth muscle cells, several membrane proteins display altered function and expression, but without an understanding of how their membrane expression is controlled, development of new therapeutics to treat hypertension remains a distant dream. The group's research will continue to investigate trafficking mechanisms of specific membrane proteins, such as ion channels and receptors, that are dysregulated in vascular disease.
The overarching theme of the group's research is to reveal and investigate new mechanisms that regulate arterial tone in order to improve our understanding of how vascular diseases develop, such as hypertension and atherosclerosis, and identify novel therapeutic targets. We have multiple ongoing research projects, but below are the two major research areas on which the group are focused currently.
Microtubules and Hypertension
This project investigates microtubule regulation of arterial tone and determines whether targeting microtubules can help treat hypertension. The group made the seminal finding that microtubules can regulate arterial tone (Lindman et al., 2018; Hypertension). These findings revealed an entirely new pathway for regulating vascular smooth muscle and suggest the microtubule network is extremely important for dictating ion channels and receptors that control arterial tone.
The laboratory has multiple ongoing projects to investigate the precise mechanisms underlying microtubule-regulation of specific ion channels and receptors that are important for controlling vascular tone.
During exercise, arteries surrounding the exercising skeletal muscle are able to dilate even though sympathetic activation and intravascular norepinephrine is increased, which would normally cause a vasoconstriction. This vasodilatation is crucial to match the enhanced metabolic demand of active skeletal muscle. The mechanisms responsible for this important physiological phenomenon - termed functional sympatholysis - remain a mystery 90 years after it was first described. In vascular diseases such as hypertension and atherosclerosis, functional sympatholysis is impaired, which is a major contributor to the inadequate supply of blood flow to muscle thereby reducing one’s ability to exercise. Determining the underlying mechanisms of functional sympatholysis would resolve a 90 year challenge in cardiovascular physiology, potentially allowing for novel therapeutic targets to improve functional capacity and thereby quality of life in populations suffering from inadequate blood flow supply to skeletal muscle.
We are always looking for motivated Bachelors, Masters and PhD students to join the Vascular Biology Group and work on these ongoing projects:
- The dynamic instability of the microtubule network in vascular smooth muscle
- The role of microtubule motor proteins in arteries and hypertension
- The role of microtubule-associated proteins in arteries and hypertension
- Characterise ion channels and receptors that are dependent on the microtubule network
- The impact of different vasoconstrictors on physiologically important relaxation pathways
- How do arteries change during exercise (Functional sympatholysis)?
- The effect of paracetamol metabolites on arterial reactivity
Anthony Michael Mozzicato - PhD Student
Anthony comes from the USA, and moved to Denmark to pursue a Master’s degree in Human Biology at University of Copenhagen. During his thesis, Anthony utilized a mass spectrometry-based approach to identify protein secretions into the extracellular matrix of skeletal muscle, in response to exercise. In August 2020, Anthony began his PhD under the Thomas Jepps’ group, studying post-translational modifications of tubulin in mesenteric arterial vessels. He is using a combination of mass spectrometry-based techniques, paired with a physiological background, in order to study the manipulation of microtubules for investigating hypertension. When Anthony is not in the lab, he enjoys training and playing football with friends.
Jennifer van der Horst – PhD Student
Originally from The Netherlands, Jennifer obtained her Master’s degree in Cardiovascular Research at the VU University in Amsterdam. With her interest in vascular research she accomplished her master thesis project in Thomas Jepps’ group in Copenhagen where she focused on the microtubule network in smooth muscle cells of the arterial wall, identifying a new mechanism that regulates arterial tone. In March 2019, Jennifer commenced her PhD during which she will continue to investigate this novel mechanism in the vasculature. She works with murine models and the myograph technique to investigate changes in arterial tone of isolated blood vessels. In addition to working in the lab, she is enjoying the challenge of developing a new life in Denmark, has joined an international group of friends and has discovered bouldering.
Joakim Bastrup - Postdoc
Joakim comes from Denmark where he obtained his Master’s degree in Molecular and Medicinal Biology at Roskilde University. His master’s thesis was carried out at the pharmaceutical company H. Lundbeck A/S working on whole-brain tissue clearing techniques such as CLARITY and iDISCO. Funded by the Innovation Fund Denmark, Joakim continued as an industrial PhD fellow at H. Lundbeck A/S in collaboration with Aalborg University studying the peptidomic and proteomic complexity of amyloid plaques in Alzheimer’s disease using different imaging and mass spectrometry (MS) techniques. In July 2020, he joined Thomas Jepps’ group at University of Copenhagen as a postdoc investigating the microtubule network of vascular smooth muscle cells in hypertension using live imaging and discovery-based MS methods. In his spare time, he enjoys travelling with his wife and playing football.
Salomé Rognant - PhD Student
Salomé comes from France where she obtained her Master’s degree in Cellular Engineering at the Poitiers University with a focus on physiology. During her first internship at the Department of Veterinary and Animal Sciences of Copenhagen University she studied the effects of compounds commonly used in equine medicine on the voltage-gated potassium channel Kv11.1. Her second internship took place in the French company Adocia where she has the opportunity to focus on developed formulation’s biocompatibility assessment. Subsequently she moved to Copenhagen to be part of Thomas Jepps’ group as a PhD Student. With her background in physiology, she is investigating the impact of the microtubules network on the electrophysiological properties of smooth muscle cell of the arterial wall. She is using the patch-clamp technic to study the different ion channels involved in arterial tone. Besides being in the lab, she loves running and art house cinema.
Thomas Jepps – Acta Physiologica Rising Star Award 2019
Thomas Jepps – Invited to speak at the August Krogh Club “Rising Stars in Physiology” symposia 2019 '
Jennifer van der Horst – Winner of Best Poster Presentation at the Annual Scandinavian Vascular Research Symposium 2019
Jennifer van der Horst – Winner of Best Oral Communication at the British Pharmacological Society Main Meeting, Pharmacology 2018
Thomas Jepps – Selected to attend the 68th Lindau Nobel Laureate Meeting
2019: Lundbeck Young Investigator Award. 10,000,000DKK - Microtubules in the vasculature – from bench to bedside
2019: Danmarks Frie Forskningsfond. 2,313,919DKK – How do microtubules regulate vascular tone?
2017: Carlsberg Foundation, Research Fellowship. 1,178,053DKK – Microtubules in Arteries
2015: Lundbeck Foundation, travel stipend for an international laboratory stay at the University of California, Irvine, U.S.A. in Prof. Geoffrey Abbott's laboratory. 20,000DKK
2015: Lundbeck Foundation, Postdoctoral Fellowship. 700,000DKK – The role of KCNE subunits in arteries.
2014: Marie Curie Postdoctoral Fellowship, which is supported by the European Commission under the William Harvey Research Institute (WHRI)-Academy fellowship programme. €199,809 – How do KCNE subunits orchestrate arterial tone?