The Lloyd Lab

Welcome to the Lloyd Lab at the Johns Hopkins School of Medicine!

Diseases

  1. Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease affecting primarily motor neurons, leading to paralysis and death within 3-5 years. Since 2003, many new ALS genes have been identified that implicate RNA metabolism, autophagy, and the cytoskeleton in disease pathogenesis. We are studying these ALS genes and cellular processes using Drosophila and human iPS (induced pluripotent stem cell) models.

    The most common genetic cause of ALS is a GGGGCC repeat expansion in the C9orf72 gene. Using Drosophila and iPS models, we have found that disruption of nuclear import is an early and fundamental event in the pathogenesis of ALS and other neurodegenerative diseases.

  2. Charcot-Marie-Tooth Disease (CMT) is an inherited, genetically heterogeneous disease causing degeneration of motor and/or sensory axons, causing slowly progressive peripheral neuropathy. Over 130 genes are now known to cause different forms of CMT, and many of these genes regulate organelle trafficking events within neurons. We can quickly study the effects of CMT mutations in Drosophila models to understand how mutations cause disease.

    Using a Drosophila model of CMT type 2C, caused by mutations in the TRPV4 gene, we have found that TRPV4-mediated neuropathy is caused by increased calcium leading to a block in axonal transport of mitochondria.

  3. Inclusion Body Myositis (IBM) is the most common acquired muscle disease in adults over the age of 50 years old. Interestingly, there are many pathological similarities between IBM and ALS (for example, TDP-43 accumulations in muscle of IBM patients resemble the TDP-43 accumulations seen in motor neurons in ALS). Furthermore, there are some genes such as Valosin Containing Protein (VCP) that when mutated can cause IBM in some family members, and ALS or CMT in others. We use Drosophila and mouse models, and human tissues, to study the underlying cause of this degenerative muscle disease.