Gilbert Di Paolo, Ph.D.
Distinguished Scientist and Executive Director
Discovery Biology
Denali Therapeutics, Inc.
Dr. Gil Di Paolo received a Ph.D. in Biology from the University of Lausanne in 1998, studying the role of microtubule regulators, stathmin and SCG10/Stathmin-2, in neuronal differentiation and survival in the lab of Dr. Gabriele Grenningloh at the Glaxo Institute for Molecular Medicine in Geneva. Gil subsequently conducted his postdoctoral studies at Yale University in the lab of Dr. Pietro De Camilli, where he discovered novel roles for phosphoinositide signaling in regulation of clathrin-mediated endocytosis and synaptic vesicle trafficking at mammalian synapses. In 2005, he obtained a Faculty appointment at Columbia University Medical Center and at the Taub Institute for Research on Alzheimer’s Disease and The Aging Brain, where he revealed a role for phosphoinositide and phospholipase signaling in the synaptotoxic actions of Ab and autophagy. He then moved to Denali Therapeutics Inc. in 2016 to pursue his translational research on the role of lipid and immunometabolism dysregulation as well as endolysosomal dysfunction in neurodegenerative disorders. His team discovered a role of TREM2 and APOE in cholesterol metabolism and inflammation. They co-developed a brain-penetrant agonist clinical candidate antibody to TREM2 (DNL919) to enhance microglial functions in AD, identified novel lysosomal functions for progranulin and co-developed a brain penetrant progranulin biotherapeutic (DNL593) for GRN-associated frontotemporal dementia, which is currently in clinical development.
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