Our laboratory conducts both human genetic and basic science research. We are working to uncover the genes involved in brain development and to better understand how their proteins function.
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Basic Science Research Projects >> Human Genetic Research Projects

Our laboratory is interested in the cellular and genetic mechanisms that govern the development of the cerebral cortex, the largest structure of the mammalian brain. The cerebral cortex represents a folded sheet of neurons that wraps around the brain to form its most outer layers. During early embryonic stages, dividing progenitor cells in the proliferative regions deep within the brain give rise to neurons of the cortex. The progenitor cells form post-mitotic cortical neurons in a fixed sequence, which migrate long distances away from the proliferative region and into the cortex before differentiating. Therefore, the steps of mitotic and post-mitotic neuronal development occur in different places and can be studied as discrete processes of proliferation, migration and differentiation. Additionally, we can take advantage of mutations known to systematically disrupt cortical development to investigate the underlying basic biology of the brain.

Somatic mutations cause a variety of human brain diseases, including autism and a continuum of cortical dysplasias (D'Gama et al. 2018, Lim et al. 2017, D'Gama et al. 2015, D'Gama et al. 2014).

Single cell whole genome sequencing can be used to study rates of mutation in the human brain to track human brain development and neurodegeneration (Lodato et al. 2017, Woodworth et al. 2017, Evrony et al. 2016, Lodato et al. 2015, Evrony et al. 2015, Cai et al. 2014, Evrony et al. 2012).

Transcriptional profiling of cerebral cortical cells shows that transcriptomes drive cortical development in humans through classification of neuronal subtypes (Zhang et al. 2016, Johnson & Walsh 2016, Johnson et al. 2015).

Human brain development is regulated by genomic loci that have undergone accelerated evolution in humans and are mutated in some human brain diseases (Doan et al. 2016, Hill & Walsh 2012).

Analysis of the embryonic cerebrospinal fluid proteome was carried out by mass spectrometry on human fetal and embryonic rat CSF to investigate for factors influencing brain development (Lehtinen et al. 2010, Zappaterra et al. 2007).

The role of the apical complex in controlling cell proliferation and cell survival is illustrated by rapid cell death and loss of cerebral cortical development observed when Pals1 is knocked out in neuronal progenitor cells (Kim et al. 2010).

The role of centrosomal proteins in neurogenesis is evidenced by randomized spindle orientation and mitotic arrest in neural progenitor cells of Cdk5rap2 knockout mice (Lizarraga et al. 2017, Hu et al. 2014, Lizarraga et al. 2010).
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