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Students

David Outland
MSc Physics / Ludwig-Maximilians-Universität (LMU) Munich

PharMetrX Research+ Program
PhD student year: 2022

University of PhD: University of Potsdam
Supervisor: Prof. Wilhelm Huisinga
Co-Supervisor: Prof. Charlotte Kloft
Mentoring I-Partner: SANOFI

PhD Project

A Model of Vascular Regulation with a Special Focus on the Mechanics of Endothelial Cell Complexes

The vascular system is the domain of many important human diseases such as strokes, heart attacks, thrombosis, hypertension as well as rarer diseases such as cerebral cavernous malformations. A common distinguishing property of all these diseases is the importance of the interaction with blood flow and thereby the dependence on its macroscopic physical properties in addition to potentially perturbed regulatory biochemical processes. Besides the blood flow a central component of the system of vascular regulation is the vessel geometry, which describes the general shape of the blood vessel including its diameter. For given system parameters, the influence of vessel geometry on blood flow is determined by hydrodynamic relations. The influence of blood flow on vessel geometry however is realized through biochemical pathways which are triggered by mechanical changes in blood flow and drive subsequent changes in vessel geometry. In this regard the endothelium forms the interface between these mechanical physical and biochemical regulatory processes. As the innermost layer of the vascular wall, it is exposed to the mechanical forces exerted on the vessel by the flowing blood. It can sense these forces and trigger biochemical pathways that can lead to changes in vessel shape such as dilation or constriction of the blood vessel. The endothelial cells enable the mechanical force sensing through different molecular components thought to be able to react to mechanical cues of the blood flow by translating them into biochemical signals. These properties give endothelial cells a cornerstone position in the system of vascular regulation.

Our aim is to better understand the vascular regulation system of blood flow and vascular geometry with a strong focus on mechanical aspects. As the mediators between the mechanical and biochemical processes endothelial cells are of central interest in this pursuit.

We approach this question by:

1) Developing a mechanical model of endothelial cell complexes considering intercellular dependencies and allowing for reaction to mechanical stimuli
2) Embedding the endothelial cell model into a model of the broader system of vascular regulation and using it to infer relevant parameters from endothelial cell junctional data

Ultimately, we seek to develop a model able to act as an aid to find adequate drug targets by leveraging its simulation capabilities to extrapolate to experimentally inaccessible domains.

Publications

Please see the list of all publications and PhD theses.

Education

  • 06/2022: Entering PharMetrX
  • 01/2022-04/2022: Research assistant, Max-Planck-Institute for Astrophysics, Garching
  • 11/2020-09/2021:  Student assistant, Max-Planck-Institute for Neurobiology, Martinsried
  • 10/2018-01/2022:  M.Sc. Physics, Ludwig-Maximilians-Universität, Munich
    - Master Thesis in the Information Field Theory Group: “Inferring Deep Sea Bioluminescent Activity from Astrophysical Neutrino Data”
  • 10/2015-08/2018: B.Sc. Physics, Ruprecht-Karls-Universität, Heidelberg
    - Bachelor Thesis in the Physics of Complex Biosystems Group: “Computer Simulations of Growing Clusters”