Dr. Li Gan is the principal investigator for project 1. Dr. Gan is a senior investigator at Gladstone Institutes and a professor at the University of California, San Francisco. Dr. Gan’s research has combined biochemical and functional approaches to dissect tau toxicity for the past decade. She will extend her discovery of the role of tau acetylation to tau degradation and synaptic toxicity.

Dr. Ken Kosik is the principal investigator for project 2. Dr. Kosik, a professor at the University of California, Santa Barbara, has made important discoveries in Tau pathobiology and stem cell biology. At the beginning of his career, Dr. Kosik was among the first to describe tau protein in Alzheimer neurofibrillary tangles. Those early studies led to the cloning of human tau, the first description of developmentally-regulated tau splicing, the role of tau in neuronal polarity, and the first identification of the tau E3 ligase. Dr. Kosik has also made important discoveries in stem cell biology using system-based approaches.

Dr. Ana Maria Cuervo is the principal investigator for project 3. Dr. Cuervo is a professor at Albert Einstein College of Medicine and a world expert in autophagy. Dr. Cuervo’s lab identified the molecular machinery that mediates translocation of substrates into lysosomes via chaperone-mediated autophagy (CMA). She also discovered a new type of autophagy, endosomal microautophagy (e-Mi), which represents a new site of interaction between endocytic and autophagic pathways, and a connection between autophagy and exosome biogenesis and extracellular release.

Dr. Nevan Krogan is a senior investigator at the Gladstone Institutes and the director of the Quantitative Biosciences Institute at the University of California, San Francisco. He also oversees the Mass Spectrometry technology center at Gladstone. Dr. Krogan’s laboratory focuses on the development of novel mass spectrometry¬–based approaches, genetic interaction screening platforms, and computational tools for data analysis. His team’s findings have provided unprecedented insights into the function, structure, and mechanisms of many molecular networks and pathways. Using an affinity purification-MS (AP-MS) strategy, they comprehensively characterized HIV-human protein-protein interactions (PPIs). Additionally, they developed a new algorithm, MIST, for scoring PPIs. Apart from PPIs, the lab pioneered the characterization of multiple post-translational modifications (PTMs) in a global, unbiased manner. They also developed other new computational tools for studying PTMs. One example is PTMFunc, which prioritizes PTMs by their likelihood of being functionally important based on location at protein-protein interfaces, evolutionary conservation, and proximity to other regulated modifications.

Dr. Martin Kampmann heads the CRISPRi/a technology (CRISPR core). Dr. Kampmann is an assistant professor at the University of California, San Francisco. Dr. Kampmann’s lab is at the forefront of developing technologies to perturb gene function in a wide range of biological systems. Dr. Kampmann co-developed a genetic screening platform that exploits catalytically dead Cas9 (dCas9) to recruit transcriptional repressors or activators to endogenous genes to enable inducible and reversible repression (CRISPRi) and activation (CRISPRa) of genes in human cells, enabling genome-wide loss- and gain-of-function screens. This screening platform is based on a quantitative framework for massively parallel screens they had previously developed for RNA interference-based screens. Importantly, CRISPRi overcomes the problem of off-target effects that has plagued RNAi-based approaches, resulting in high specificity while maintaining high sensitivity.

Dr. Lea T. Grinberg heads the Human Biology Validation core (Human core). Dr. Grinberg is a neuropathologist with extensive expertise in neuropathology and brain banking. Her research focuses on early stages of neurodegenerative diseases in humans and method development. To lead the core, Dr. Grinberg is joined by Dr. Bruce Miller who is the director of the UCSF/Memory and Aging Center (MAC), principal investigator of the NIH-funded UCSF Alzheimer’s Disease Research Center, and director of the project on frontotemporal dementia (FTD) called “Frontotemporal Dementia: Genes, Images and Emotions” since 2002. Dr. Miller’s interest in FTD dates back to the 1980s and he oversees comprehensive assessment of patients, as well as the collection of bio-specimens and postmortem human tissue banked at the MAC.

Dr. Giovanni Coppola heads the Data Coordination core (Data core). Dr. Coppola is an associate professor at the University of California, Los Angeles. The Coppola lab specializes in web-based databases and handling of large datasets. As director of the NINDS-funded UCLA Informatics Center for Neurogenetics and Neurogenomics (ICNN), the UCLA Semel Center for Informatics and Personalized Genomics, and the Functional Genomics Core for two foundations (the Adelson Research Medical Foundation and the Tau Consortium), Dr. Coppola is involved in large-scale DNA and RNA sequencing projects and is developing integrative analytical methods for multi-dimensional high-throughput data. The Coppola lab constitutes the Genetics core for the previously mentioned project at UCSF and the Genetics core for the Frontotemporal Lobar Degeneration Clinical Research.