Christopher M. Gomez, M.D., Ph.D.

APPOINTMENTS

  • Chair, Department of Neurology
  • Albina Y. Surbis Professor, Commitee on Molecular Medicine/MPMM

EDUCATION

M.D., University of Chicago, 1983

Ph.D., University of Chicago, 1981

CONTACT INFORMATION

The University of Chicago 
AMB S237 (MC 2030)
5841 South Maryland Avenue 
Chicago, Illinois 60637

 cgomez@neurology.bsd.uchicago.edu

Phone:  (773) 702-6390

RESEARCH SUMMARY

Molecular and Genetic Causes of Neurodegenerative Disease

Christopher M. Gomez concentrates his research program on the molecular and cellular mechanisms of neurodegenerative disease, with a particular focus on the means by which genetic mutations in ion channels or other essential proteins lead to dominantly inherited neurodegenerative diseases. In dominantly-inherited neurodegenerative diseases neuronal death arises because the genetic mutation alters, sometimes quite subtly, rather than abolishes the function of the disease protein. Altered function of ion channel molecules, proteins that are critical to neuronal activity, can impair neuronal viability through a variety of mechanisms. His laboratory pursues two primary project avenues, one on the genetics and pathogenesis of the slow-channel syndrome, a model disease of excitatory synaptic degeneration, the other representing a similar focus on genetically-determined spinocerebellar ataxias (SCA). Several forms of SCA are associated with mutations in ion channel genes. He also helps lead the Cooperative Ataxia Group, a national consortium of ataxia specialists devoted to enhancing clinical research in ataxia and launching clinical trials for the SCAs.

The slow-channel syndrome is a chronic, usually congenital neuromuscular disease that causes progressive fatigability and weakness sometimes leading to death through respiratory failure. The disease is due to mutations in the genes that encode the acetylcholine receptor of the neuromuscular junction and thus is passed from parent to offspring. The mutations alter the acetylcholine receptor function making it leaky, which causes the neuromuscular synapse to become overloaded with sodium and calcium ions. The Gomez group has used both patient biopsy material and transgenic mouse models to determine that the degenerative process involves both pre and post synaptic structures and degenerative pathways that include the activation of several cysteine proteases. His group is currently developing therapeutic strategies using genetic approaches to selectively block these degenerative pathways in the muscle fibers.

Spinocerebellar ataxia type 6 (SCA6) is a form of progressive cerebellar ataxia appearing in middle age that gradually leads to total incapacitation due to severe incoordination of all motor functions. Severe imbalance and gait instability progresses to wheelchair confinement. Oropharyngeal and upper limb incoordination disrupt the ability to perform activities of daily living including speaking, eating, and grooming. Erratic eye movements impair vision. The disease is associated with progressive degeneration of the cerebellar Purkinje cells and is due to a mutation in a gene encoding the major calcium channel of the cerebellum. The Gomez group has found that this mutation, which is a type called an expanded polyglutamine (polyQ) tract that is seen in other neurodegenerative diseases, alters the function of calcium channel protein in at least two fashions. First, as with the slow-channel syndrome, the expanded polyQ tract makes the calcium channel leaky, potentially leading to calcium overload of Purkinje cells and activation of degenerative pathways as is seen in that disorder. More importantly, they have discovered that the C terminal portion of the calcium channel that contains the polyQ tract is actually a form of nuclear signaling protein that is cleaved from the channel and transported to the nucleus. C terminal calcium channel proteins that contain the expanded polyQ tract are toxic to neurons and appear to cause damage by disturbing the DNA repair pathways. The Gomez lab is now delineating the normal and pathological actions of the calcium channel C terminus using biochemical cellular and genetic approaches.

Research Papers in PubMed