Systematic elucidation of cellular networks controlling proteinopathy in Alzheimer’s disease

The goal of this research project is to combine three powerful and innovative technologies to the study of gene combinations and drugs that control the formation of plaques and tangles in Alzheimer's disease, with the long-term goal of understanding the network of genes controlling all aspects of Alzheimer's disease. The project will take a big data approach to the problem, and use techniques including: 1) computational analysis of an unprecedented “big data” set of 360,000 triple-screened drug compounds, 2) the massively parallel functional interrogation of all human genes and hundreds of thousands of gene combinations, and 3) high throughput behavioral analysis of gene and drug effects in a novel zebrafish model of Alzheimer's disease.

Affiliated Investigators

Martin Kampmann, Ph.D.

University of California, San Francisco

Dr. Martin Kampmann is an Assistant Professor in the Department of Biochemistry & Biophysics and the Institute for Neurodegenerative Diseases at the University of California, San Francisco. He spearheaded the development of a functional genomics platform that makes it possible to robustly identify human genes relevant to a cellular process of interest, and to elucidate cellular pathways and networks using systematic genetic interaction maps. The focus of Dr. Kampmann's research is the network maintaining the functional state of cellular proteins, termed the proteostasis network. Dr. Kampmann aims to elucidate how the proteostasis network is challenged and rewired in diseases, especially cancer and neurodegenerative diseases. Identification of proteostasis factors that control formation, spread, and clearance of protein aggregates associated with neurodegenerative diseases will shed light on the disease mechanisms and reveal potential therapeutic targets. Dr. Kampmann has recently been awarded a Pathway to Independence Award by the National Institutes of Health.

Michael Keiser, Ph.D.

University of California, San Francisco

Dr. Michael Keiser is an Assistant Professor in the Department of Pharmaceutical Chemistry and the Institute for Neurodegenerative Diseases at the University of California San Francisco, with a joint appointment in the Department of Bioengineering & Therapeutic Sciences. He led development of a new systems pharmacology platform to predict unexpected drug activities and side effects, the Similarity Ensemble Approach. His lab investigates how small molecules strike “chords” of multiple targets at once to perturb cellular and disease networks. A major focus of this work is on the discovery of chords for neurodegenerative diseases, where therapeutics acting through polypharmacology may enable entirely novel treatment routes. Previously, Dr. Keiser co-founded a start-up company, after training at UCSF and Stanford University. Dr. Keiser has recently been selected for a Glenn Award for Research in the Biological Mechanisms of Aging.

David Kokel, Ph.D.

University of California, San Francisco

Dr. David Kokel is an Assistant Professor in the Department of Physiology and the Institute of Neurodegenerative Diseases at the University of California San Francisco.  He developed a platform for combining high throughput behavioral phenotyping with large-scale chemical screening in zebrafish.  A major goal of Dr. Kokel’s research is to discover novel neuroactive compounds and understand their effects on the brain and behavior.  Before joining UCSF, Dr. Kokel was an assistant Professor at Harvard Medical School.