The Lloyd Lab

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

Welcome!

The Lloyd Lab in the Department of Neurology at the Johns Hopkins School of Medicine studies the molecular underpinnings of neuromuscular diseases, including Amyotrophic Lateral Sclerosis (ALS), Charcot-Marie-Tooth Disease (CMT), and Inclusion Body Myositis (IBM). To do so, we utilize fruit fly and human cellular models of disease to better understand the cellular mechanisms of these diseases and to find novel treatments.

Lab Overview

Our laboratory is interested in understanding the fundamental molecular and cellular processes that underlie degenerative diseases of the neuromuscular system. The critical cell of the peripheral neuromuscular system is the motor neuron, a nerve cell that has its cell body and dendrites (synaptic inputs) in the spinal cord and sends long axons to the periphery to form synapses on muscle cells at the neuromuscular junction (NMJ). Perhaps due to their large size (human motor axons can have axons as long as 1 meter) and inability of cells to divide after birth, motor neurons are particularly vulnerable to degeneration with aging, and the mechanisms regulating neuron and muscle maintenance with aging are poorly understood. We are particularly interested in understanding how intracellular trafficking is disrupted in these degenerative diseases, as these processes are implicated in inherited and sporadic neurodegenerative and myodegenerative diseases.

In particular, we study:

  1. Axonal transport – the process of moving various cargo such as mitochondria and vesicles to and from the cell body to the synapse. Mutations in dynactin, a critical regulator of retrograde axonal transport, and TRPV4 cause distinct neurodegenerative diseases including inherited motor neuropathies.
  2. Autophagy – the process by which cells degrade misfolded protein aggregates and damaged organelles via transport to the lysosome. Several ALS genes are known to regulate this process, and the mechanisms of autophagy at the neuromuscular junction are poorly understood.
  3. Nucleocytoplasmic transport – we and others have shown that shuttling of proteins and RNA molecules in and out of the nucleus is a critical process for neuronal maintenance disrupted in neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) (Zhang et al, Nature, 2015; Zhang et al, Cell, 2018), and Hungtington’s Disease (Grima et al, Neuron 2017). Importantly, modulation of nucleocytoplasmic transport may be a therapeutic target for neurodegenerative diseases, and we are working with Biogen to test this hypothesis.