Introducing Dr Dr Hans Zempel

The research team led by Dr. Hans Zempel has made notable advances in several key areas of tauopathies and neurodegeneration:

• Tau Sorting Mechanisms: Dr. Zempel’s team has explored how Tau is targeted to axons under normal conditions and how this process is disrupted in disease. Theresearch examines various hypotheses, including preferential targeting via specific transport mechanisms, selective compartment specific degradation, and compartment-specific post-translational modification (DOI: 10.1016/j.neuroscience.2021.01.041; DOI: 10.1101/2024.06.28.601286)
• Tau Mislocalization and Neurodegeneration: Dr. Zempel’s research has shed light on the effects of Tau mislocalization on neuronal polarity and microtubule stability. His work highlights the role of Tau missorting and spastin-induced microtubule disruption in neurodegenerative diseases such as Alzheimer’s disease and hereditary spastic paraplegia (DOI: 10.4103/NRR.NRR-D-23-01742).
• Mitochondrial Dynamics and Tau Pathology: His team has investigated the relationship between mitochondrial function and Tau pathology, demonstrating how a cluster of mitochondria at the axon initial segment (AIS) regulates Tau trafficking. This breakthrough provides new insights into how mitochondrial dysfunction contributes to tau mislocalization in Alzheimer’s disease (DOI: 10.1007/s00018-022-04150-3).
• Genetic Factors in Tauopathies: Zempel’s work explores genetic predispositions and variants associated with both primary and secondary tauopathies, helping to uncover the genetic underpinnings of neurodegenerative disorders (DOI: 10.1016/j.neuroscience.2021.01.041, DOI: 10.1016/j.neuroscience.2021.01.041).
• Methodological Contributions: Beyond groundbreaking discoveries, Dr. Zempel and his research team have developed advanced methodologies for studying tau in human neurons, including optimized protocols for cultivating and differentiating human-induced pluripotent stem cell (iPSC)-derived glutamatergic neurons (DOI: 10.1007/978-1-0716-3629-9_29, DOI: 10.1515/biol-2022-1010).
• Model Systems and Experimental Approaches: His team has developed human iPSC-derived neurons devoid of Tau for studying tauopathies and mitochondrial dysfunction. They employ cutting-edge technologies, including: Lentiviral transduction; Advanced microscopy techniques (e.g., calcium imaging, photoconversion/optogenetics, and STED-nanoscopy); Omics approaches (e.g., RNA-seq, proteomics) to investigate disease mechanisms and test potential therapeutic approaches (DOI: 10.1002/alz.14403, DOI: 10.1007/s00018-022-04150-3, DOI: 10.1101/2024.06.28.601286, DOI: 10.1515/biol-2022-1010).
• Gene Editing and Gene Therapy: The team has used CRISPR-edited iPSCs to create cellular models that closely mimic tauopathies and mitochondrial dysfunction. They successfully knocked out MAPT and knocked down POLG, resulting in decreased mitochondrial function, closely resembling patient conditions. Their viral transduction methods and AAV vector development are paving the way for gene therapy trials (DOI: 10.1002/alz.14403).
• Clinical and Translational Research: Dr. Zempel’s team has secured regulatory approvals for two animal studies testing AAV-based therapies and ethics approval for a patient study focused on mitochondriopathies.

In summary
Dr. Zempel’s comprehensive research provides valuable insights into the molecular mechanisms of tauopathies, paving the way for potential therapeutic strategies targeting Tau mislocalization and related neurodegenerative processes. His lab’s recent advancements in gene therapy, particularly through the development of AAV-based vectors, position him as a leader in translating laboratory findings into clinical solutions for neurodegenerative diseases.

Dr. Hans Zempel’s academic journey began at the Freie Universität Berlin (FU)and Charité in Berlin, where he studied Biochemistry and Biophysics. He completed his MSc in Biochemistry in 2006. 

During his studies, he gained valuable laboratory experience through multiple international research projects. This included a six-month MSc/Diploma thesis in Biochemistry/Biotechnology at FU Berlin and Charité, as well as three-month research projects in France at the École Nationale Supérieure de Chimie de Montpellier, focusing on protein and lipid biochemistry, and in Chile at the Universidad de Santiago de Chile, where he worked on neurochemistry.

Between 2005 and 2006, Dr. Zempel expanded his academic horizons by studying at Kyoto University in Japan under a full scholarship. There, he attended courses in Biophysics, Genetics, and Japanese language and culture. He then continued his education at Tokyo Medical and Dental University from 2006 to 2008, completing the third and fourth years of the clinical medicine curriculum. During this time, he also conducted research at the Tokyo Metropolitan Institute of Aging for six months, furthering his interest in neurodegenerative diseases.

From 2008 to 2010, Dr. Zempel pursued his PhD in Structural Molecular Biology at the Max-Planck Unit for Structural Molecular Biology in Hamburg, where his work resulted in four published papers. He continued his doctoral research at the University of Hamburg and the Max-Planck Group for Structural Molecular Biology, ultimately completing his PhD thesis in Biochemistry in December 2013, graduating with summa cum laude distinction (grade 1.0).

Following his PhD, Dr. Zempel joined the German Center for Neurodegenerative Diseases (DZNE) in Bonn, where he held both PhD and postdoctoral positions from 2010 to 2017. During this period, he also pursued clinical medicine studies at the University of Bonn (2015-2018). He undertook extensive clinical training through rotations and traineeships, including seven months in Neurology at the University of Liège(Belgium), four months in Surgery at the University of Würzburg/Ansbach, and four months in Internal Medicine at the University of La Laguna (Spain).

In August 2018, Dr. Zempel earned his Medical Approbation from the University of Bonn and later received his MD (Dr. med.) in 2019 with distinction. During the same period, from April to August 2018, he served as Chief Scientific Officer at MedXact Technology Ltd. (now Juniper Medical Computing), a start-up incubated within EF in Berlin/London.

Since 2020, Dr. Zempel has been leading a research group at the Institute for Human Genetics at the Faculty of Medicine, University of Cologne, and the University Hospital Cologne. In 2022, he was appointed Group Leader as part of the Career Advancement Program (CAP) at the Center for Molecular Medicine Cologne (CMMC).

Throughout his career, Dr. Zempel has received numerous prestigious awards, including the 2022 Alzheimer Research Initiative Grant, the 2015 Steinberg-Krupp-Alzheimer-Research Award, and the Otto-Hahn-Medal for his exceptional PhD work from the Max-Planck society. He has also been recognized for his research with several other accolades, including the Nikon Young Scientist Award in 2014 and multiple scholarships throughout his academic career.

In addition to his research, Dr. Zempel has contributed to the scientific community by co-organizing the 8th Symposium of the Institute of Human Genetics at the University of Cologne and serving as a guest editor for the journal Cells. He is also an active reviewer for high-impact journals such as Science, Nature, Nature Neuroscience and other Nature Journals, and EMBO Journal.

Dr. Zempel and his team have successfully acquired six major grants, totaling over €1.5 million, to support his research. These include grants from the EKFS, DFG, AFI, and JMF, as well as several smaller grants and PhD stipends.

Since 2019, Dr. Zempel has mentored numerous students, helping them secure stipends for Master's and MD theses and supporting five doctoral candidates. His team has won multiple awards, including publication prizes, travel awards, and poster prizes.