Sarah Hedtrich is particularly interested in inflammatory and genetic diseases of the human skin and lung, such as ichthyosis, a family of rare skin disorders that affect only a small percentage of the population. “Yet the disorder severely impairs each individual patient’s quality of life,” says Hedtrich. “It is characterized by excessive keratinization of the skin, which results in the formation of scales and the lack of an intact skin barrier against pathogens, making patients prone to frequent infections, especially during childhood. People with the disorder feel disfigured and – especially in the case of newborns – struggle with high water loss through the skin, which can lead to life-threatening situations.” The genetic cause of congenital ichthyosis is a single mutation in the gene for an enzyme that enables cross-linking of the cells in the upper layer of the skin. “There is no causal treatment available, and those with the condition have to use expensive creams and ointments, which adds to the physical burden.”
A gene therapy is in the works
To help change this, Hedtrich wants to develop a gene therapy to replace the faulty gene with a working copy. “We have already identified the gene and can correct the flaw using the CRISPR-Cas gene-editing tool. The only problem is how to get CRISPR-Cas into the diseased skin cells ?” is how Hedtrich describes the biggest challenge. Systemic delivery does not work for skin diseases, which means CRISPR cannot be injected into the bloodstream or swallowed in pill form. “It has to be delivered topically, that is, directly to the affected site. A simple ointment or cream is not however sufficient as a carrier, because the keratinized skin of patients is difficult to penetrate. Jet stream injectors that use air could help here,” says Hedtrich, looking to the future. But this procedure is not far enough along yet. It first has to be tested in a model, but even that is no easy feat.
From 3D skin models to organs-on-chips
“Rodent skin is fundamentally different from human skin, and not just because of the fur,” explains Hedtrich. “So we decided to develop three-dimensional human skin models, which we are building from patients’ cells or healthy donors’ cells.” The scientist is also using so-called tissue engineering to develop bronchial epithelium models in order to provide a human model system for her second research focus, the human lung. “Our goal is to create an organ-on-a-chip that contains blood vessel-like structures, which even simulate blood pressure using special pumps,” she says. “This is because such models are very good at emulating processes in the human organism.” Hedtrich is convinced that this applies not only to diseases of the skin and lung epithelium: “Much of the failure in drug development is due to the fact that results obtained in mice or rats cannot be translated to humans. Using complex human models can help improve translation, and would therefore bring great advantages not only in terms of animal welfare.” Hedtrich would like to use her professorship for exactly this purpose: to develop translational human models.
Professor Christopher Baum, Chair of the BIH Board of Directors and Chief Translational Research Officer of Charité – Universitätsmedizin Berlin, is pleased to welcome the new professor: “Developing alternatives to animal research is taken very seriously at the BIH and Charité. We are committed to reducing or replacing animal testing as much as possible. With her expertise in human organ models, Sarah Hedtrich will be great asset to us.”
Aiming for translation
Hedtrich is delighted to be joining the Berlin Institute of Health: “It’s not always easy for a pharmacologist like myself to gain access to patients. That’s one of the big advantages of the BIH: basic researchers here work closely with physicians at Charité. That makes translation possible, because it brings lab bench discoveries to the bedside.” That perfectly sums up the BIH’s motto: “Turning research into health.” The BIH also will also give her an opportunity to work with experts in related fields – like regenerative medicine, organoids and stem cells – who complement her own expertise.
Hedtrich studied pharmaceutical sciences in Leipzig before earning a doctorate in pharmacology from Freie Universität Berlin (FU). She then held postdoctoral positions at LMU Munich and Tufts University in Boston. From 2013 to 2015 she led a junior research group at the FU’s Institute of Pharmacy, and in 2015 she became an Assistant Professor at the FU. In 2019 she was named an Associate Professor at the University of British Columbia in Vancouver, Canada. Hedtrich is married and has two children, aged 3 and 5.
About the BIH Johanna Quandt Professorships
Stiftung Charité and the BIH have jointly launched the BIH Johanna Quandt Professorships (temporary W2 professorships with a genuine tenure track). The novel professorship scheme targets specifically female scientists in order to provide an impetus for the promotion of equal opportunities in the life sciences. The professorships are filled through an international recruitment process and include a binding option for permanent tenure as a lifetime professorship (genuine tenure track). In addition, the professorships are open to all topics, offering the applicants the opportunity to develop the orientation of their professorships themselves, also beyond the usual biomedical disciplines, and to have an innovative impact on the BIH’s translational mission. Along with the three Johanna Quandt Professors selected in 2017, a total of seven BIH Johanna Quandt Professorships will enrich the life sciences in Berlin by the end of this year (see also the press release by Stiftung Charité from August 31, 2021, at https://www.stiftung-charite.de/infos-presse/presse).