Lawrence Rajendran, M.D.

Co-Director and Velux Stiftung Professor

Systems and Cell Biology of Neurodegeneration | Psychiatry Research

University of Zurich, Switzerland

Prof. Lawrence Rajendran combines systems biology and cell biology approaches to understand the complexity of neurodegenerative diseases and is a renowned expert in the cell biology of Alzheimer’s disease. He studied the mechanisms by which cells regulate the production of the amyloid b (Ab) peptide, a central molecule in the pathogenesis of Alzheimer’s disease. Particularly, he studied the involvement of lipids and membrane trafficking in Ab metabolism and using biochemical, genetic and cell biological tools. He identified Rab5/EEA-1positive early endosomes to be the organelles responsible for Ab production. In addition, he discovered a novel exosomal pathway through which the Ab peptides could exit the cell to accumulate in the form of amyloid plaques. The identification of the secretory vesicle route for amyloid secretion aids now in the understanding of how amyloids can spread in the brain. He is also the founding member of the International Society for Extracellular Vesicles. Two years after identifying the subcellular organelle responsible for Ab production, he showed that b-secretase, the rate-limiting enzyme in Ab production, can be efficiently inhibited if a soluble b-secretase inhibitor is targeted to the endosomes via membrane anchoring. This work provided key insights into designing effective drugs for membrane-associated targets. 

With the Cure Alzheimer Fund grant, Rajendran aims at developing APP-specific b-secretase inhibitors for effective, side-effect-free treatment for Alzheimer’s disease. In the last few years, he has expanded his research with an aim of quantitatively mapping the human genome in the light of Alzheimer’s disease. He recently showed that the late-onset AD genes differ fundamentally from the early onset mutations in their influence on Ab metabolism. 

He received several awards and honors for his work. His honors include the German Neuroscience Society's Schilling's prize, the Breuer Award, the National Medal of Honor and the President’s Prize by the Govt. of Panama, German Alzheimer’s Hirnliga’s Steinberg-Krupp Prize, Outstanding Young Investigator award of the Alzheimer’s Drug Discovery Foundation, The Boehringer Ingelheim Apopis Prize, European Neuroscience Society Award and a University gold medalist in both Bachelors and Masters. Rajendran featured in the 2009 World's top 100 Scientists. Rajendran has published in many high-ranking journals and serves in many important scientific advisory boards and steering committees including the Zurich Neuroscience Center and the AD/PD Scientific Advisory Board. He is the founder of the Facebook platform for the ISEV. He was an Associate Editor at the Journal of Alzheimer’s disease, Journal of Extracellular Vesicles and Frontiers in Alzheimer’s disease and the Editor in Chief of Neurodegenerative Diseases. On the social work front, Rajendran is the founder of Raise.Rural, a non-profit organization that provides research opportunities for students from the rural parts of the world. 

Funded Research

Project Description Researchers Funding
Development of an APP-specific B-secretase inhibitor for Alzheimer’s disease therapy

Developments of disease-modifying therapeutics that can slow or ultimately halt disease progression are urgently needed for treating Alzheimer’s disease (AD). Till date all anti-amyloid measures to treat AD have failed. This is often construed as amyloid being the wrong target but most of the amyloid-reducing approaches including targeting the amyloid producing enzymes have side effects. An attempt to develop a specific therapy with minimum mechanism-based side effects is proposed here.

2014
$100,000