"Membrane trafficking and targeting in Alzheimer’s disease"
Alzheimer’s disease (AD) is the most common form of neurodegenerative disease and prevalent in the aging population. It is estimated that roughly 37 million people around the world will suffer from some form of dementia by 2025. The most extensive European epidemiological studies (Wimo et al. 2003; Ott et al. 1995) shows that 72% of all dementia patients suffer from AD. An estimated 4.5 million Americans have AD. The number of Americans with AD has more than doubled since 1980 and will continue to grow such that by 2050 the number of individuals with Alzheimer’s could range from 11.3 million to 16 million.
There continues to be no cure for AD and basic research continues to fuel efficient drug discovery. By studying the basic biology of Alzheimer’s disease, we aim to develop efficient strategies to inhibit some key processes associated with the disease. A characteristic feature of the disease is the presence of plaques in the brain accompanied by the formation of insoluble tangle-like structures that accumulate inside the brain cells.
A predominant hypothesis suggests that a small peptide that usually accumulates in the plaques clumps together and causes the neurodegeneration observed in the disease. This peptide is produced from another molecule, termed amyloid precursor protein (APP), when two enzymes called ß- and ɣ-secretases act on it to release the peptide. By efficiently inhibiting the production of this peptide, one could develop a therapeutic strategy for Alzheimer’s disease.
By studying how the cells make this peptide and what are the criteria for the enzymes to produce this peptide, recently our lab developed a new inhibitor for the first enzyme, ß-secretase. In the framework of this project, we aim to study how this peptide becomes toxic in the cells and what are the cellular requirements for this toxicity. If one understands the mechanism by which the cell produces the toxic clumps of this peptide, we could develop novel inhibitors to efficiently inhibit this process for the treatment of Alzheimer’s disease.
|June 2009 – present||University of Zurich, Medical Faculty, Co-Director & Assistant Professor, Systems & Cell Biology of Neurodegeneration|
|Nov 2007 – June 2009||Max Planck Institute of Molecular Cell Biology and Genetics, Germany, Principal Investigator, Alzheimer Forschung Initiative project & BMBF-FORMAT project “Membrane intervention and systems biology approaches for AD therapy”|
|July 2003 – Nov 2007||Max Planck Institute of Molecular Cell Biology and Genetics, Germany, Postdoctoral fellow with Kai Simons, M.D., Ph.D.|
|2003-2007||Postdoc Cell Biology and Neurosciences, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
(Cell biology of Alzheimer’s disease)
|2001-2003||PhD Immunology (Natural Sciences), University of Konstanz, Konstanz, Germany. Thesis: Role of Membrane microdomains in Leukocyte polarity and signaling|
|1997-2000||Pre-PhD Molecular Biophysics, Indian Institute of Science, Bangalore, India Folding of Lectins and artificial chaperone assisted folding of proteins|
|1995-1997||MSc Molecular Biology, University of Madras, Madras, India|
|1992-1995||BSc Biochemistry, University of Madras, Madras, India|