Prof. Dr. Dirk Roggenbuck
Titel der Dissertation:
Investigation of drugs in mono- and multi-medication on age dependent and physiologically relevant liver cell models in 2D and 3D culture
Demographic development in Germany currently follows a global trend of industrially strong nations. The structure of age has changed from the "classic pyramid shape", as it was still seen in the 20th century, to a "mushroom shape": the proportion of older people is increasing, while the proportion of young people is decreasing. This redistribution of the population in terms of age is not only of economic but also of medical interest. The ageing process brings physiological changes that influence pharmacodynamics and pharmacokinetics. Thus, drug toxicity increases sevenfold during the ageing process from 20 to 79 years. This is mainly caused by an age dependent size reduction and reduced blood flow of the liver by 28% to 44%, which is in turn associated with a reduced metabolism.
With this background, the aim of this work is to look at mono- and multi-medications from an age-physiological perspective. Many elderly patients take several different drugs daily and only little is known about their metabolism, their effects and side-effects with respect to reduced liver functions. For this purpose, we will establish physiologically relevant liver cell models from primary hepatic cells of elderly patients. This will be achieved using the upcyte methodology that was established by Prof. Küpper. Upon “upcyting”, defined proliferation genes will be introduced in primary cells by lentiviral transfer. These cells retain their physiological functions and keep proliferating for about 20 passages without being tumorigenic. These cell models will then be treated with different drugs in mono- and multimedication. The behavior of the cells will be compared to untreated controls as well as to younger liver cell models. The effects of the different drugs will be investigated first in classical 2D culture, and later on in more sophisticated and more relevant 3D culture systems.
I received my Bachelor in Biotechnology in 2019 at the Brandenburg Technical University Cottbus-Senftenberg with the thesis "Development of a method to determine antibiotic sensitivity in bacterial biofilms using fluorescence microscopy" in the Department of Multiparameter Diagnostics under the supervision of Prof. Dr. Peter Schierack During this time, I developed a growing interest in researching new things and further developing already known possibilities. So I decided to continue my Master's degree, also at the BTU, in order to be able to do my own research on my own projects later on. I successfully completed my Master's degree in 2020 with the project "Differentiation of progenitor cells into neutrophil granulocytes for the application of serological diagnostic test systems". Directly afterwards I began my dissertation with a GRS fellowship in the Department of Molecular Cell Biology under the supervision of Prof. Dr. Jan-Heiner Küpper, Prof. Dr. Dirk Roggenbuck and Dr. Sarah Kammerer.
Titel der Dissertation:
Cartilage regeneration using a co-culture model of human primary chondrocytes and osteoblasts
Osteoarthrosis (OA) is the most common age-associated joint disease worldwide, affecting at least 10 million people in Germany alone. It is a degenerative joint disease, which leads to the degradation of cartilage tissue as well as influences adjacent bones, muscles, joint capsules and ligaments. The disease is the leading cause of chronic pain in joints and mobility limitations, especially in the elderly. The resulting limitations can lead to a reduced quality of life with an increased use of medical services, which ultimately results in increased morbidity. Conventional therapies for osteoarthrosis are limited and consist primarily of pain management and muscle strengthening through physical exercises. However, osteoarthrosis cannot be healed and a joint replacement is required.
The aim of the research project is to develop a novel cell-based osteoarthrosis therapy. Since both cartilage and bone are affected in OA, a co-culture model based on the connection and interaction of cartilage- and bone-like microtissues should be developed and established. The source of cartilage (chondrocytes) and bone cells (osteoblasts) are condyles of patients undergoing knee replacement surgery. Initial experiments will focus on the optimisation of the differentiation of chondrocytes and osteoblasts alone in a 3D environment. Further experiments will then establish techniques for the co-culture of both cell types or cell-based microtissues.
Since I am not able to comprehend and unravel the mysteries of the universe, my love for biology and chemistry were the subjects guiding me in school towards the future. Already when working towards my graduation in school, I set my mind on studying Biotechnology and regenerating organs in a lab. In the end, I chose to start my Bachelor in Biotechnology at the University of Applied Sciences in Senftenberg (later Brandenburg University of Technology Cottbus-Senftenberg) because the study programme is highly practice-based. During my practical term and my Bachelor thesis, I was at the research group of Prof. Dr. med. Ingo Kutschka at the University hospital in Magdeburg working on induced pluripotent stem cells to generate heart tissue. Afterwards, I also studied my Master in Biotechnology at the BTU with the focus Cell Biology. During my Master thesis I did not generate any tissues and instead analysed the effects of a substance on the angiogenic process induced by endothelial cells. But as I still wanted to regenerate tissues and someday whole organs, I took the opportunity to join the laboratory of Prof. Ursula Anderer in 2018. After working in the laboratory for nearly two years, I decided to do my dissertation at the research group and received a scholarship from the Graduate Research School in 2019. Besides my passion for Tissue Engineering, I love reading, writing and hiking. And learning more about the mysteries of the universe.