Karl-Herbert Schäfer, MD
Consultant (anatomy), MD, Dr. med., Professor of Biotechnology
|EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)|
|INSTITUTION AND LOCATION||DEGREE
|YEAR(s)||FIELD OF STUDY|
|Humanistisches Knaben-Real-Gymnasium St.Ingbert
|University of Saarland,||1979||Biology|
|Medical School, University of Saarland, Homburg, Germany
|Department of Anatomy, Medical School, University of Saarland, Homburg, Germany||1986-1988||Anatomy/
|Department of Surgery, St. Joseph Hospital, Neunkirchen, Germany
|Department of Anatomy, Medical School, University of Saarland, Homburg, Germany||
Consultant in anatomy, Dr. med,
|Department of Pediatric Surgery, Clinical Hospital Mannheim, University Heidelberg, Germany||1999-2001||Pediatric Surgery|
|University of Applied Sciences Kaiserslautern, Germany||Professor||2001 until now||Biotechnology|
Positions and Employment
1986-1988 Research Assistant Department of Anatomy, University of Saarland, Germany
Principal Investigator: Pedro Mestres, MD
1988-1991 Resident, Department of Surgery, St. Joseph Hospital, Neunkirchen, Germany
1991-1999 Research Assistant Department of Anatomy, University of Saarland, Germany
Principal Investigator: Pedro Mestres, MD
since 1995 Consultant for Anatomy
1999-2001 Resident, Department of Pediatric Surgery, Clinical Hospital Mannheim, University Heidelberg, Germany
since 2001 Full professor of Biotechnology at the University of Applied Sciences Kaiserslautern, Germany
2006-2009 Head of the study course Applied Life Sciences (Bachelor)
since 2009 Head of the study course Applied Life Sciences (Master)
since 2017 Vice President Research and Transfer University of Applied Sciences Kaiserslautern
Other Experience and Professional Memberships
1999-Present Member, German Society of Neurogastroenterology and Motility
1995-Present Member, German Association of Anatomists
2003-2013 Member, Society of Neuroscience
2009-Present Member, Biomedical Engineering Group, UAS Kaiserslautern
2007-Present German Stem Cell Society
since 2002 Ad Hoc Reviews for the German Research Foundation (DFG)
since 2004 Ad Hoc Reviews for the German Assosication of Indurstrial Research (AIF)
since 2006 Research Foundation Flanders-FWO Reviews
since 2006 Member of the Research Centre for Integrated miniaturized Systems (IMS)
since 2012 Accreditation committee for biomedical study courses (ASIIN)
2016 Evaluation of INSERM group, Haut Conseil de l’évaluation de la recherche et de l’enseignement supérieur (HCRES)
Honors and Awards
1999 Nomination Soave Award (Colorectal Club), Stockholm
2003 Novartis Award, Graz Austria (Together with Stefan Holland-Cunz)
2008 Travelling Fellowship German Research Foundation (At the GI Division at the University Stanford)
2013 Nomination, Academic Award of Rhineland Palatinate
2014 Acquisition of a Carl-Zeiss-Foundation Professorship
2015/16 Nomination Teaching Award of Rhineland Palatinate
CONTRIBUTIONS TO SCIENCE
Neural Crest Derived Stem Cells
Based on two scholarship I spent 1992/93 at the University College in London, I started to work on isolated myenteric plexus cultures. In those days I worked with Kristjan Jessen, Rhona Mirsky, Jill Saffrey and Geoff Burnstock. Back in Germany, I started to investigate the role of individual neurotrophic factors, such as bFG, BDNF and later GDNF on the ENS. In one study, we could show that the effect of GDNF on neurite outgrowth in enteric neurons lasts beyond birth, but does decrease with incrasing age. We also investigated the role of the microenvironment, be it the extracellular matrix or the surrounding smooth muscle tissue. In following studies by others, it could be demonstrated, that these smooth muscle effects were based on GDNF secretion. A very important aspect was also the influence of the pathological microenvironment, that is described in more detail in the next paragraph.
Based on the studies from the nineties, where we already realized that there was a great growth potential in the isolatated early postnatal ENS cells, we started to focus on neural crest derived stem cells from the embryonic gut. We could succesfully isolate and expand these cells from both mouse and even human embryonic gut. We have been the first group to describe the generation of both mouse and human enteric neurospheres. These cells have already been transplanted in aganglionic smooth muscle tissue from Hirschsprungs patients. Due to our expertise in the isolation and cultivation of neural crest derived stem cells, I was invited (2008) by PJ Pasricha to perform a scholarship at the University of Stanford to help to establish these techniques in their working group.
Currently, we are developing methods to transplant these cells in a way, that all aganglionic tissue is reached, without the need of many individual injections. This is performed by an intraarterial injection of huge amounts of dissociated enteric neurospheres.
We also recognized the enormous potential of the human ENS as an autologous neural stem cell source. Here, the approach to the adult ENS is more appropriate, but also much harder to achieve. Techniques for the isolation of both postnatal and adult myenteric plexus have been developed for mice and men. We introduced the appendix as an easily accessible part of the gastrointestinal tract, from which we can isolate and expand neural stem cells in appropriate numbers. Based on our work, these approaches are currently used by other groups as well.
Role of the ENS in gastrointestinal diseases
Based on the work on isolated and dissociated myenteric plexus, we were also interested in the impact of gastrointestinal diseases on the ENS. Coming from pediatric surgery, the first focus was on the situation in Hirschsprungs disease. Funded by the German Research Counsel (DFG) we investigated the impact of the pathological microenvironment on both isolated myenteric neurons and neural stem cells. A very important aspect for the use of cellular therapies in Hirschsprungs disease is the the aspect of a peremissive microenvironment of the pathologically altered gut wall. We therefore investigated the smooth muscle compartment in Hirschprungs patients along the gut axis in the areas resected from the diseased children. Here we could demonstrate that there is a changing amount of neurotrophic factors (GDNF), respectively transcription factors (TGF-ß) from the ganglionic to the transition zone and the aganglionic segments. Nevertheless, the situation was never non-permissive, as could be demonstrated by culturing both dissociated myenteric plexus and enteric neurospheres in media, conditioned with protein solutions, derived from the various gut segments in Hirschsprungs disease. So we could pave the way for future cellular therapies, that can only be successful, when the transplanted cells can integrate in the diseased tissue. Based on our work I was approached by different clinical groups to collaborate on the role of enteric glia in Crohns disease or the ENS in pancreatic cancer. Here we developed i.e. new approaches to investigate the mutual interaction between enteric neuronal cells and pancreatic cancer cells, thus demonstrating the importance of the enteric innervation in the propagation of cancer cells.
Currently we are investigating the changes of the ENS due to inflammatory or microbiome alterations. To do so, we stimulate ENS cultures with microbial products, such as LPS or develop co-culture techniques for the ENS and individual bacterial phylae.
Technical improvents in gastrointestinal research
A very important aspect of our current work is based on the embedding of our group into a rather technical and engineering environment. My professorship is placed in the faculty of informatics and microsystem technologies, which allows the close interactions and collaborations to improve both technical equipment and analytical software. This resulted in interesting projects that allowed to establish i.e. microsystems for the simulation of the mucosal barrier in an in-vivo-equivalent way. Micromachined channels were manufactured in polymer sheets, so that pairs of these sheets can be arranged orthogonally with an interposed polycarbonated microporous membrane. This system allows to culture ENS cells on one side of the membrane in the upper channel system, and enterocytes on the opposite side of the membrane in the lower compartment. A very important principle in this approach is the reduction of media volume in which the cells are growing. In contrast to conventional culture systems, released factors by the cells have a much higher impact in autocrine loops on the cultured cells. We currently develop multi organ culture chambers where we apply similar principles. A patent is pending for this system so that I cannot present details.
We also tried already very early to mimick the in vivo situation in vitro, by the use of co-culture systems, or 3D-cultures with extracellular matrix components. The latter led to a much more realistic growth of dissociated myenteric plexus, that rearranged to in-vivo like ganglia. This system could also be used to investigate mutual interactions of different cell types that communicate intensely in vivo, such as nervous tissue and endothelia or, as already mentioned, nervous system and cancer cells.
We are also integrating electrical recordings systems in the culture approaches. These are based either on multielectrode array recordings or impedance measurement systems.