As part of our virtual 'Special Guest Seminars' series, the UK DRI is delighted to welcome Prof Christian Haass.
Prof Christian Haass
Professor of Biochemistry and Head of the Department of Metabolic Biochemistry at the Biomedical Center (LMU, Munich) – DZNE Coordinator, Munich.
Microglial modulation in neurodegenerative disease – innovative therapies or devilish gambling?
Monday 20 April, 13:00 - 14:00 BST
This event is open to UK DRI researchers and support staff only. Registration and associated Zoom links will be distributed via Centre Manager emails nearer the time of the event.
Prof Haass started to work on Alzheimer's disease (AD) in 1990 at a time, when very little was known about the cellular mechanisms involved. Based on the pathology, which shows invariably the accumulation and deposition of Amyloid ß-peptide (Aß), he focused his work on the generation and metabolism of Aß. Christian Haass hypothesized against the widely accepted general opinion in this field that Aß may be produced from its precursor in a physiologically normal pathway and not necessarily in a pathological process. Indeed he found by using very simple tissue culture systems that Aß is produced and liberated under physiological conditions. This pivotal finding was a major breakthrough for the entire field, since it allowed elucidating the molecular principles behind Aß generation as well as the identification of the enzymes (the so-called secretases) involved in generation and liberation of the peptide and finally the development of selective inhibitors to therapeutically lower Aß production in patients. Christian first concentrated on the cellular mechanisms behind Aß production. Doing so he made a number of major observations: Two enzymes, which he called beta- and gamma-secretase produce Aß, while a third enzyme, alpha-secretase, prevents Aß generation. Moreover, beta-secretase was found to be the rate limiting enzyme and gamma-secretase to be a rather unusual protease cleaving within the hydrophobic environment of a membrane. Using his tissue culture assay he was able to demonstrate how mutations, which cause very aggressive familial variants of AD, affect production of Aß, a finding which provided strong support for a major pathological role of Aß and which was the basis for the amyloid cascade hypothesis.
Current work of the Haass lab supports the idea that TREM2 is protective in AD patients. Based on his fundamental research on TREM2 function Haass in collaboration with Simons (DZNE Munich) and Denali Therapeutics developed a novel therapeutic strategy. With the help of an antibody they stabilize signaling competent TREM2 on the cell surface to boost TREM2 protective functions.
Main contact for enquiries: Dr Giovanna Lalli