Prof. Christian Haass was born in Mannheim at Germany in the year 1960. After his academic education in Biology in RuprechtsKarls University in Heidelberg, he completed his PhD in "cDNA cloning proteasome subunits". In his postdoctoral training he was a fellow in the Laboratory of Prof. D J Selkoe at the Centre for Neurological Diseases at Harvard Medical School in Boston, USA.

 

After an extremely successful 25 yeasr postdoctoral period with three Nature papers, a publication in J. Neuroscience, and two papers in J. Biol. Chem., he became an assistant professor for Neurology (Neuroscience) at Harvard Medical School ( 1 993 -1995). In the summer of 1995, he assumed a new position as an Associate professor (tenure) at the Central Institute for Mental Health, Mannheim/University of Heidelberg. At this time he was one of the youngest professors in Germany. Only three years later, he was recruited to Munich to become the Professor of Biochemistry at the Faculty of Medicine of the Ludwig MaximiliansUniversity of Munich and Director of the Department of Biochemistry at its Adolf-Butenandt-Institute. Dr. Haass' rapid academic advancement is emblematic of his groundbreaking and remarkably productive scientific contributions.

 

Alzheimer's disease     (AD) is currently one of the most threatening health problems, which our aging society is facing. Millions of patients are suffering from this devastating disorder and we must even expect a sharp increase in the number of the patients in the near future due- to steadily increasing life span. Without treatment of AD, the entire health care system around the world will collapse very soon and all modern economies will face one of their strongest challenges in the very near future. Currently no treatment is available. Huge efforts are required to identify targets for an AD slowing therapy. Not surprisingly thousands of scientists are working world-wide on the molecular cellular mechanisms of AD. One of the most brilliant molecular biologists in this field is Prof. Dr. Christian Haass. 

Not resting on his ability in cell biology and biochemistry, Dr. Haass sought out gifted collaborators, such as Dr. Ralf Baumeister, in the area of genetics and began incorporating in vivo bioassays for the function of the presenilins into his research. This led to a number of highly important insights. For example, Haass, Baumeister and colleagues were able to show that wild-type human presenilin fully complements the deficiency of the PS homologue in C. elegans sel-12, but AD-causing missense mutations in human presenilin conferred only partial and incomplete recovery. This turned out to be one of the first in vivo demonstrations thatpresenilin 1 has a direct function in Notch signaling and that this function can be affected by FAD mutations.

 

Then he showed that APP, Notch, and CD44 all undergo a dual cleavage mediated by the same y-secretase complex. This finding was crucial for the proposal of a direct involvement of PS in y-secretase cleavage of APP and other substrates and finally proved that all y-secretasesubstrates are cleaved by the same PS dependent y-secretase activity. Very recently, Dr. Haasscould even demonstrate that this dual cleavage mechanism appears to be a generally used pathway by a family of novel intramembrane proteases, which he just identified in zebra fish. The identification of the dual cleavage mechanism has profound implications on the generation of y-secretase inhibitors, drugs aimed to slow A β generation in human patients. Obviously, such drugs must be designed in a way that they do not prevent physiological processes such as Notch signaling. The development of such drugs would have been impossible without Dr. Haass' crucial findings. 

Based on the work of Dr. Haass' laboratory a completely new family of aspartyl proteases was defined (the GxGD-type aspartyl protease). This knowledge turned out to be extremely important for the development of selective y-secretase inhibitors. In fact, Dr. Haass and his co-workers are just about to identify the sequence requirements within and around this active site motif, which leads to the selective cleavage of Notch or APP. This is of pivotal importance, since Dr. Haass found that y-secretase inhibitors designed to slow A β generation during the disease, all cause severe side effects due to their inhibition of Notch signaling.

 

Atthistime Dr. Haass' work was so strongly recognized thatthe Deutsche Forschungsgemeinschafthonored him with the most prestigious German research award, the Gottfried Wilhelm Leibniz Award. This Award is given to the most successful German scientists in all fields of science. In the same year Dr. Haass also received the Potamkin Award of the American Academy of Neurology as well as the Ernst Jung Award for Medicine. This clearly demonstrates that Dr. Haass became an internationally well accepted as leader in his field.

 

Dr. Haass then made a number of highly important discoveries, which led to the understanding of the molecular composition, assembly, and function of the y-secretase complex. Dr. Haass demonstrated that Nicastrin (Nct) is a crucial component of the y-secretase complex. As the first scientist in AD research he used the RNAi technology to down- regulate expression of disease associated proteins (in that case Nct). This led to the spectacular finding that Nct is absolutely required for y-secretase function and consequently A β production. In addition this paper also provided the first evidence for a coordinated regulation of y-secretase complex components. In that regard Dr. Haass could demonstrate that the down- regulation of Nct was followed by a loss of PS expression. Moreover, in cells which lack PS, Dr. Haass could show that Nct fails to maturate. These findings led to the principal understanding of the regulated complex assembly of y-secretase (PNAS, 2002).

 

The discovery in     1 997 of mutations in the y-nsynuclein as in rare forms of familial Parkinson's disease    (PD) gene led him to develop transgenic mice for this second most common neurodegenerative disorder. He introduced the required methodology into his new lab in Munich and rapidly created several as-expressing mouse lines. He and his colleagues showed that the mice accumulate human as in neuronal cell bodies and swollen neurites. Only two years later Dr. Haass showed that these mice produce typical Lewy bodies in an age and gene-dosage dependent manner. In the same publication Dr. Haass proved his very provocative hypothesis that y-synuclein may also undergo a conformational change during its pathological deposition similar to the prion protein. Based on these findings, he introduced a novel method, which allows the very sensitive detection of y-synuclein associated pathology. Furthermore, this finding provided further evidence for a unifying molecular mechanism of neurodegenerative disorders.

 

Dr. Haass is a frequently asked expert for review articles in major journals. His incisive reviews have appeared in journals such as Cell, Neuron, Current Opinions, Trends in Neuroscience, Science, Nature, Molecular Cell Biology, and Journal of Cell Biology etc. A perusal of Dr. Haass' bibliography will quickly show that he has a remarkable ability to generate numerous parallel experimental studies, execute them meticulously and publish rigorous, elegant data in highly competitive journals. As a result of the number and importance of his contributions, Dr. Haass has become one of the top biomedical scientists in the area of human neurodegenerative disease worldwide.

 

Dr. Haass also "restarted" German and European research into neurodegenerative disorders. In summary, Dr. Haass is an intellectually highly gifted and- methodologically sophisticated scientist who has made major contributions to our growing understanding of the cause and mechanism of Alzheimer's disease and now Parkinson's disease. His research in both fields (Alzheimer as well as Parkinson) will have direct implications for the development of therapeutic approaches. Therefore, Professor Christian Haass is truly worthy of being awarded in Biology of Aging, the Harridan Award for Medical Research Excellence 2005-2006 for his outstanding contributions as an innovative scientist in the study of human neurodegenerative disease.