BBS Faculty Member - Corey Harwell

Corey Harwell

Department of Neurobiology

Harvard Medical School
Armenise Building 345
200 Longwood Avenue
Boston, MA 02115
Tel: 617-432-5529
Email: corey_harwell@hms.harvard.edu



The goal of our research is to understand the cellular and molecular mechanisms that regulate the cellular diversity of the cortex and the precision of it network connections.

The cortical network is composed of a diverse array of neuronal subtypes, which work together to regulate many of our most complex behaviors and cognitive functions. One major focus in the lab is to understand how this diversity is achieved and identify the key molecular programs that influence the fate decisions of progenitor cells. Once cells have decided their fate, they must navigate a sea of potential synaptic partners to form precise connections. We are also interested in understanding the cellular and molecular events that guide the assembly of cortical circuitry. It has become clear that perturbations in either the production of diverse neuronal cell types or the assembly of the circuit can lead to a variety of cognitive disorders including intellectual disability, schizophrenia and autism spectrum disorder. Gaining a better understanding of the important molecular pathways that guide cortical circuit development may one day lead to new therapies for many of these disorders.

Current projects in the lab are focused on:

1.
Understanding the cellular mechanisms underlying inhibitory interneuron diversity. Inhibitory interneurons are amongst the most diverse neuronal cell types in the brain, in both form and function. Using retroviral lineage tracing we found that multiple subtypes of interneurons are derived from the same mother progenitor. We are currently using a combination of retroviral lineage tracing, and time-lapse imaging to understand how the proliferative behavior of interneuron progenitors regulates the production of diverse cell types

2.
Understanding the role of Sonic Hedgehog signaling in cortical circuit development and function. We have previously shown that cell type specific expression of Sonic Hedgehog (SHH) signaling components regulates synapse formation between distinct subsets of neurons. Utilizing genetics anatomy and electrophysiology we are currently focused on understanding the precise cellular interactions that are regulated by SHH signaling which function guide synaptic specificity during circuit formation.



Last Update: 4/3/2015



Publications

Putz U*, Harwell C*, Nedivi E (2005) “Soluble CPG15 expressed during early development rescues cortical progenitors from apoptosis”, Nature Neuroscience 8(3): 322-331. (*co-first authors) PMID: 15711540

Harwell C, Burbach B, Svoboda K, Nedivi E (2005) “Regulation of cpg15 expression during single whisker experience in the barrel cortex of adult mice”, Journal of Neurobiology 65(1):85-96. PMID: 16010668

Ihrie R, Shah J,
Harwell C, Levine J, Guinto C, Lezameta M, Kriegstein A, Alvarez-Buylla A. (2011) “Sonic Hedgehog Regulates the Positional Identity of Neural Stem Cells in the Adult Brain", Neuron 71(2):250-62. PMID: 21791285

Harwell C, Parker P, Gee S, Okada A, McConnell S, Kreitzer A, Kriegstein A (2012) “Sonic Hedgehog Expression in Corticofugal Projection Neurons Directs Cortical Microcircuit Formation” Neuron 73(6):1116-26. PMID: 22445340



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