Tom Lloyd MD, Ph.D
Assistant Professor of Neurology and Neurosciencetlloyd4@jhmi.edu
Telephone Number: 410-955-2227
Fax Number: 410-502-5459
John G. Rangos, Sr. Building
855 N. Wolfe Street
Baltimore, MD 21205
Neuronal intracellular transport in development and disease
Motor neurons are the largest (and longest!) cells in the body, and intracellular organelles and other molecular complexes must be transported bidirectionally to distinct regions of the axon, dendrite, or synapse. While many of the molecular motors that transport organelles such as mitochondria and synaptic vesicles along axons are known, little is known about how this transport is regulated. Given the complexity and importance of this process, it’s not surprising that disruption of axonal transport has been implicated in many neurological diseases, including motor neuron degenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Charcot-Marie-Tooth (CMT) disease.
Our goal is to understand how axonal and synaptic transport is regulated, and how these processes are disrupted in neurodegenerative disease. Our primary model organism is Drosophila due to the tremendous power of the fruitfly in performing genetic screens. We are currently performing both forward and reverse genetic approaches to identify and characterize novel regulators of axonal transport and modifiers of neurodegeneration. For example, we have introduced disease-associated mutations in dynactin, a protein complex that regulates the dynein retrograde motor, and we are studying the mechanisms whereby mutations disrupt intracellular transport and cause motor neuron degeneration. Finally, phenotypic characterization of motor neuron degenerative disease models including FUS and TDP-43 are underway to better understand how mutant proteins cause disease. In collaboration with other investigators of the Robert Packard Center for ALS Research at Johns Hopkins and the Brain Science Institute, we hope to translate insights learned from fly models of ALS into new therapeutic targets for disease.