member

Research Description

We develop theory and dynamical systems tools, machine learning and data analysis algorithms, and whole brain mapping methods to characterize and understand flexible brain function

Current Projects

Research Description

RESEARCH DESCRIPTION

We investigate molecular underpinnings of brain resilience in aging and neurodegenerative disease – through study of the hormone klotho and research on sex chromosomes. Our research spans discovery at the intersection between mechanisms of aging and neurodegenerative disease. We use a wide variety of techniques to uncover cellular and molecular mechanisms using cellular models, mouse models, and human populations.

The role of cell surface diversity in the assembly of neural circuits

Decoding human genetic disease allows us to develop models of the pathology that can be directly tested with gene correction or targeted drug therapy. Dominant negative mutations are particularly promising therapeutic targets since they are resistant to traditional therapies, yet precise excision of disease-causing allele could provide a cure. We are using patient-derived induced pluripotent stem cells (iPSCs) to model diseases in tissues that are particularly susceptible to dominant negative mutations: cardiomyocytes, motor neurons and retinal pigment epithelial (RPE) cells.

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.

Late Cortical Neuron Development in the Human Brain and Neurodevelopmental Disorders

Cellular and Molecular Dissection of the Breathing Rhythm Generator

Research in my laboratory focuses on the molecular and cellular basis of neural circuit wiring and rewiring, using the mouse retina as a model, with the goal to reconstruct neural circuits and restore physiological functions subject to neurological diseases and neuronal injuries. My previous work addressed how defined subtypes of neurons wire up during retinal development (Duan et al Cell, 2014), and how defined subtypes of retinal ganglion cells mediate axon regeneration in response to injury (Duan et al, Neuron, 2015).