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Research Topic

Degeneration, dysfunction, injury and repair of the nervous system

Mission Statement

The Baas Laboratory focuses on the underlying mechanisms of neurodegeneration and dysfunction of the nervous system, resulting from degenerative diseases, developmental disorders and injury, with the goal of developing therapies for prevention, treatment and repair. Rather than focusing on just one type of disease, disorder or injury, we focus on a common downstream target that goes awry across almost all of them. By focusing downstream, we can gain mechanistic insights and develop therapies that can broadly apply across maladies. This enables each lab member to have a distinctive project while keeping everyone on a unified mission. Specifically, the downstream target we study is the microtubule – a cytoskeletal structure that is critically important for all aspects of the architecture, intracellular transport and mobility of neurons and other cells of the nervous system.

Research

Project 1. Neurodevelopmental Disorders

As neurons develop from mitotic precursors, they undergo a migratory journey to their final locations in the brain or elsewhere in the body. Axons develop with growth cones heralding their journey to their targets, and dendrites form as well. Both axons and dendrites undergo extensive branching, pruning and remodeling. All of these events are microtubule-based, with the relevant proteins and pathways vulnerable to disorders such as autism. For over 30 years, we have worked to elucidate the mechanisms, proteins and pathways of neurodevelopment to enable us to have unique insights into such neurodevelopmental disorders that we are now studying.

Project 2. Hereditary Spastic Paraplegia

Hereditary spastic paraplegia (HSP) is (usually) an adult-onset disease that most often arises due to autosomal dominant mutations of the SPAST gene, which encodes for a microtubule-severing protein called spastin. The patients have a pronounced gait deficiency and eventually become confined to a wheelchair, due to corticospinal degeneration. Our focus on microtubules has provided us unique insights into the etiology of the disease, which we are studying with various experimental models. In the past we have used cultured rodent neurons and Drosophila , but now we are using a mouse model for HSP that we have developed that displays the hallmark characteristics of the disease. We are conducting behavioral, anatomical and histochemical studies, pursuing molecular mechanisms, and are now poised to begin testing therapies. We also have developed human induced pluripotent cell lines (hiPSC) from patients with the disease, which we are differentiating into neurons, for further analyses of mechanisms and potential therapies.