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Tobias Huber – interested in biology and life

Prof. Dr. Tobias Huber’s specific and major interest concerns the most hidden structures of the human body of all things. Huber and his team at the Freiburg University Medical Centre are investigating the structure, genetics and function of the kidneys, which are the most important natural filtering organs in the human body. Working with researchers from the BIOSS cluster of excellence, Huber identified a signalling pathway which has been shown to cause diabetic nephropathy, and also came up with solutions to reverse the situation. He has been awarded numerous prizes, including recently, the American Society of Nephrology Young Investigator Award.

Kidney expert Prof. Dr. Tobias Huber © private

Tobias Huber was born in Waldkirch in 1971. As a child, he already had a keen interest in biology. He used to breed amphibians, butterflies and other insects and owned several aquariums. He spent his time observing badger setts and foxholes from homemade hides while his contemporaries were playing football. “I’ve always enjoyed being out in the countryside; we lived close to a forest, so I did not have to go very far to do what I enjoyed most; I was extremely interested in natural living things,” said Prof. Huber who is now a medical doctor and kidney specialist. 

During his community service period in the surgical emergency department at the Freiburg University Medical Centre, Huber decided to study medicine. He loved working with patients and this led to his decision to focus on a hospital career. “I was extremely interested in science, but I was equally thrilled by how scientific findings could be used for the benefit of patients,” Huber says. He spent some of his study period in the USA and in Austria (Vienna), but in the end he decided to return to Freiburg. He is still an active researcher and doctor, doing basic science, but always with a focus on the application of findings to patients. 

Huber regards the fact that he ended up in the field of nephrology as one of life’s coincidences, as it was basically the fascination for the spirit of his former mentors, Prof. Dr. Hermann Pavenstädt and Prof. Dr. Rainer Greger, that drew him towards this subject. “It could have been any other subject,” said Huber pondering why he chose nephrology of all subjects, “and meeting the scientists who became my mentors is what got me interested in kidneys.”

A foster child of the German Research Foundation

During his doctoral thesis, Huber cultivated podocytes, highly specialised renal filter cells, in order to study them using the patch clamp technique. In addition, he succeeded in identifying angiotensin surface receptors. Angiotensin receptor blockers are nowadays used for preventing kidney failure in people with diabetes, to name but one example.

In 1999, Huber joined Prof. Dr. Gerd Walz in the Department of Nephrology at the Freiburg University Medical Centre as an assistant doctor, where he started to use molecular biology methods for the analysis of the podocytes and their long, regularly spaced interdigitating foot processes that are connected through the slit diaphragm through which the blood is pressed into the kidneys. In addition to exploring these structures, Huber cloned new genes of the Neph-Nephrin family which encode proteins of the renal filter. These proteins do not only have a structural function and are needed for the maintenance of the complex glomerular architecture, they also transduce signals that prevent cells from dying.

Huber was awarded an Emmy Noether grant by the German Research Foundation (DFG), which enabled him to spend some time at Washington University in St. Louis (USA) where he obtained further insights into renal function on a different level. “I was then able to take my insights into renal function to the next level. Instead of using molecular biology methods, I started to use animal models in the form of transgenic mice.” At the age of 35, Huber was awarded a DFG grant to establish an Emmy Noether research group and he returned to Freiburg to establish his own research group. He was later also awarded a Heisenberg scholarship and in February 2013 a Heisenberg professorship. “I am a foster child of the German Research Foundation,” said Huber laughing. “I have practically gone through the DFG’s four excellence programmes one after the other,” Huber continued. He is convinced that this was the key to his success. All his positions have been financed with third-party funds, which gave him the independence and flexibility he needed for carrying out research whilst undergoing specialist training to become a nephrologist.

The Achilles heel of many kidney diseases

Diabetic nephropathy is triggered by the mTOR signalling pathway in patients suffering from diabetes mellitus. © Prof. Dr. Tobias Huber, Freiburg University Medical Centre
Huber has been focussing on the renal filtration system, its composition, function and defects for around 15 years now. Every kidney has around one million filtering units known as renal corpuscles. The blood is filtered in the glomerulus, a tuft of capillaries that are lined with podocytes. Substances that are no longer needed enter the ureter and are excreted in the urine. The long foot processes of the podocytes wrap around the glomerular capillaries and interdigitate with those of adjacent podocytes, forming filtration slits through which the blood is pressed into the kidneys. The filtration slits are made up of nephrins, transmembrane proteins that are necessary for the proper functioning of the renal filtration barrier. “When a structure is as complex and differentiated as the renal filter, then its cells are usually no longer able to divide,” Huber says, going on to add, “and this inability to replenish the cell pool is what makes this structure the Achilles heel of many kidney diseases.” Huber and his co-workers, who are all as enthusiastic as Huber, have identified numerous regulatory mechanisms that lead to the development and maintenance of such structures. One of these regulatory mechanisms is the mTOR (mammalian target of rapamycin) signalling pathway which plays a crucial role in the pathogenesis of diabetic nephropathy. This disease develops from longstanding diabetes mellitus, and is the most frequent cause of kidney failure and therefore a prime indication for dialysis. Podocytes regulate their size by way of the mTOR signalling pathway. If one of these specialised cells becomes defective, mTOR signalling triggers other podocytes to grow, expand and close the gap. This pathway is deregulated (i.e. hyperactive) in patients with diabetes, which leads to unlimited growth and loss of podocytes. “When the cells have grown to a specific size, they dedifferentiate and eventually fall off,” said Huber explaining the underlying mechanism. “These podocytes will not be replaced by new ones, but by connective tissue structures, which leads to the progressive scarring of the filter.”

“We want to find solutions”

Huber’s team of researchers works well together. © Prof. Dr. Tobias Huber, Freiburg University Medical Centre

Huber’s team is specifically focused on analysing structures that are invisible in vivo, establishing systems that advance our understanding of complicated organs and finding starting points for new therapies. The researchers have already achieved some success in the therapy of diabetic nephropathy, at least in the mouse model. “We were able to interrupt the mTOR signalling pathway with rapamycin; this prevented experimental mice from developing the disease,” said Huber. However, rapamycin has many adverse effects. This is due to the fact that rapamycin interferes with the pathway very early on. Huber’s team is therefore looking for more subordinate targets. 

Huber calls for an open research community and is not afraid of competition. He believes that people who do not disclose data before they are published have an exaggerated sense of their own importance. “Isn’t it research that counts, obtaining the results that are for the benefit of the patients?” says Huber.

Further information:

Prof. Dr. Tobias Huber
Department of Nephrology and General Medicine
Freiburg University Medical Centre
Hugstetterstr. 55
79106 Freiburg
Tel.: +49 (0)761/ 270-35590
Fax.: +49 (0)761/270-32700
E-mail: tobias.huber(at)uniklinik-freiburg.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/tobias-huber-interested-in-biology-and-life