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Overview

We are an interdisciplinary group working on several interrelated questions in neuroscience. We combine computational, theoretical and experimental approaches in this quest. Current efforts are focused on two major themes. The first theme involves using single-cell genomics to gain a deeper understanding the molecular basis of the diversity of neurons across the brain. We use this as a foundation to understand the development and evolution of neural diversity, and its implication for disease pathogenesis. The second theme focuses on using continuum physics to understand ion transport and electrostatic effects near membrane interfaces, and exploring its implications for neuronal signaling. Our work is highly collaborative, and we have active collaborations with experimental neuroscientists, molecular biologists and clinicians.  

Below, we highlight a few ongoing projects and previous work.

Understanding the genomic basis of neuronal diversity

The brain is comprised of diverse types of neurons that vary in form and function. We have pioneered approaches in single-cell genomics to chart the molecular diversity of cell types in the retina, the thin neural film in the eye that initiates vision. In collaboration with neuroscientists, we have also shown that these molecular atlases can be harmonized with morphology and physiology. Our single-cell genomic analyses of the mouse retina can be found in multiple papers over the past several years. For example, Shekhar et al., Cell, 2016 and Tran*, Shekhar* et al., Neuron, 2019 describe comprehensive atlases of retinal bipolar cells and ganglion cells in mice, respectively. Goetz et al., Cell Rep, 2022 describes collaborative work to unify morphology, function and transcriptomics for retinal ganglion cells in mice.  Peng*, Shekhar* et al., Cell, 2019 and Yan et al., Sci. Rep., 2020 describe the classification of the primate retina in macaques and humans. A detailed review of this work is presented in Shekhar and Sanes, Ann. Rev. Vis. Sci., 2021.

The Nature vs. Nurture axis in early neuronal development

A central question in developmental neuroscience is how the diverse types of neurons in the brain are generated, and how they assemble into highly elaborate circuits that govern our sensory perceptions, feelings and memories. We have attempted to address this question in two different parts of the visual system, the retina and the cortex. 

The evolutionary history of neuronal types

Differential vulnerability of neuronal types in degenerative diseases

Spatiotemporal dynamics of diffuse charges near neuronal membranes

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