Virus-like Intercellular Signaling Underlying Autoimmune Neurological Disorders

2023 Scientific Innovations Award
Jason Shepherd, Ph.D.
University of Utah

Dr. Shepherd’s lab discovered that a brain gene critical for memory and cognition, Arc, has biochemical
properties like retroviruses such as HIV. Arc protein can form virus-like protein capsids that shuttle
RNA and proteins cell-to-cell. Other human genes have predicted similarities, but it remains
unknown if these genes have also retained virus-like properties. They found that another family of
genes that are also expressed in the brain can form capsids. These paraneoplastic Ma antigen
(PNMA) genes sometimes cause neurological disorders when abnormally expressed in certain
kinds of cancers due to an autoimmune response. It is unclear how or why these proteins activate
the immune system to generate self-antibodies. The aim of this project is to test whether abnormal
expression of PNMA virus-like capsids outside the brain are the cause of auto-antibody production
and the resulting neurological symptoms. This project will uncover new signaling pathways in the
brain and reveal the causes of some autoimmune neurological disorders.

Other Awards

Chaolin Zhang, Ph.D., Columbia University
Human-specific Alternative Splicing, Brain
Development, and Ciliopathies
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Yuki Oka, Ph.D., California Institute of Technology
Molecular Mechanisms of Osmolality Sensing in the Mammalian Brain
Animals constantly detect and process sensory signals to react appropriately. External sensory information (e.g., light and sound) serves as prominent environmental cues to guide behavior. On the other hand, our…
Angelique Bordey, Ph.D., Yale University
The Role of Ribosomes in Synaptic Circuit Formation and Socio-Communicative Deficits
Dr. Bordey and her lab’s proposal aims at identifying a molecular mechanism responsible for autism-like socio-communicative defects in the developmental disorder, tuberous sclerosis complex (TSC). TSC is a genetic disorder…
Adam E. Cohen, Ph.D., Harvard University
To spike or not to spike? Mapping dendritic computations in vivo.
The brain is made of neurons, and neurons convert synaptic inputs to spiking outputs. How does a neuron decide when to spike?