Jeremy Willsey, PhD

The Willsey lab aims to elucidate the pathobiology underlying neurodevelopmental disorders such as autism, tourette disorder, epileptic encephalopathies, and intellectual disability. To accomplish this, we focus on two main areas. First, gene discovery, as genes are the puzzle pieces we need to advance our understanding. Second, systems biological approaches that assemble these puzzle pieces, in a hypothesis-free manner, into testable hypotheses about the pathogenesis of these disorders. Our ultimate goal is a precise and (clinically) actionable understanding.

Current Projects

Psychiatric Cell Map Initiative. The Willsey lab is one of the founding members of the PCMI. Through collaborations with many other labs at UCSF and beyond, we are systematically mapping the networks and functional pathways underlying neurodevelopmental disorders, with the ultimate goal of translating the exciting gene discoveries in neurodevelopmental disorders to an actionable understanding of the underlying neurobiology. We have recently secured funding for this broad project from the NIMH and the Weill Institute for Neurosciences. Relevant Publications: Willsey et al., 2018 (in press at Cell).

Gene expression profiling of IPSC derived neurons in Autism Spectrum Disorder. As part of a recently funded NIMH R01, we are profiling gene expression signatures in excitatory and inhibitory neurons derived from patients with idiopathic autism and comparing them to neurons derived from matched controls in order to identify dysregulated molecular pathways.

Functional Genomics of Human Brain Development. The lab is involved in several grants tied to the PsychENCODE consortium. Broadly, these grants aim to build high resolution maps of human gene and protein expression profiles, as well as functional genomic elements, across brain regions, cell types, and developmental time periods. This is essential for understanding human neurodevelopment and for clarifying when, where, and what cell types are relevant to the etiology and treatment of neuropsychiatric disorders. Relevant Publications: PsychENCODE 2015 Marker Paper.

Leveraging genetic associations in autism to identify therapeutic targets. While, remarkable progress has been made in defining the human genetics of autism, its pathological underpinnings remain enigmatic and no definitive therapy has been developed. Along with the Shoichet and von Zastrow labs, we aim to move beyond the genetic architecture of autism to understand its molecular pathophysiology, and so define targets for drug treatment using a pioneering genomic-proteomic-chemical approach. This work was recently funded by a QBI Bold and Basic Award.

Gene discovery in Tourette disorder. The Willsey lab leads the TIC Genetics gene discovery efforts. This consortium leverages multiple genome-wide approaches for identifying rare, large effect size variants, focusing both on identifying highly penetrant genetic variants segregating in multiply affected pedigrees and on de novo mutations identified in simplex families. We have recently been awarded a multi-site R01 that aims to recruit 1,000 additional parent-child simplex trios, sequence these families, identify additional high confidence TD genes, and begin the process of leveraging these molecular clues to elaborate the biological basis of TD, while making all the collected biomaterials, clinical and genomic data rapidly available to the broad scientific community. Relevant Publications: Georgitsi et al., 2016; Willsey et al., 2017; Wang et al., 2018 (under review).

Gene Discovery in Neurodegenerative Disorders. We are conducting pilot whole exome sequencing of brain tissue from patients with confirmed cases of Multiple Systems Atrophy (MSA). We hope to report on these findings later this year.

Lab Members

Lab Website

Academic community service and committee membership:

NS NSF Mentor, NS Retreat co-chair, Tetrad, BMI