Transcriptional variation as a cellular phenotype

How does inter- and Intra-cell type heterogeneity contribute to cellular function?

Every cell in the brain is unique. Gene expression differences between cells of discrete types help define how they integrate and function in the nervous sytem. However, continuous sources of variation across cells, including spatial position, activity state, and responses to injury or inflammation, can have diverse functional consequences for cellular activities.

By measuring the gene expression content of single cells in their native environment we can learn how properties like regional localization, cellular morphology, axonal targets, and integration within the circuitry of the brain, contribute to observable, cell-type-specific changes in the dynamic mammalian nervous system.

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Cell fate specification during neural development

How are different cell types created from a single parental cell type in the developing nervous system?

The staggering diversity of cell types in the mammalian brain and enteric nervous system is established by only a handful of different precursor cell types. Our lab wants to understand how cells know or are instructed to become a particular cell type. This involves cataloging and identifying different cell types and their features, learning how they are integrated with each other during development to form a function nervous system, and identifying patterns of gene and gene networks that regulate choices in cell fate.

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Celltype-specific responses in health and disease

What makes certain cell types more vulnerable to degeneration in the brain?

Neurodegenerative disorders are characterized by the targeted loss of specific cellular populations in the brain. In many cases, different neurodegenerative disorders differ only in the specific neuronal populations or brain regions which are affected. We use single-cell measurements to reconstruct how different neuronal populations respond and succumb to disease-associated variants or conditions. Understanding these processes to learn why different neuronal cell types are selectively vulnerable or spared in neurodegenerative disorders provides insight into potential therapeutic options for these debilitating disorders.

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The Goff Lab supports and welcomes learners of all backgrounds

We believe in open-minded curiosity of our world and that this begins by recognizing and learning how our perceptions and biases can shape this process. We are committed to building a laboratory and training environment that is diverse and inclusive to welcome, and collectively benefit from, unique perspectives on both science and life.

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