Assistant Professor of Neurology
Phone: (412) 648-3299
e-mail: estevezm@upmc.edu

Specialized Areas of Interest

Neurodegeneration; migraine.

Biography

The primarily focus of the lab of Miguel Estevez, MD, PhD, is on using the invertebrate, Caenorhabditis elegans, to model human neurologic diseases. For example, human clinical genetics led to the identification of mutations in a P/Q-type calcium channel gene as the cause of a rare dominant form of migraine called Familial Hemiplegic Migraine. Loss of function mutations in the C. elegans ortholog of this calcium channel gene, unc-2, cause the animals to exhibit lethargic behavior and have convulsions under mild thermal stress. Using populations of animals with a loss of function mutation in this C. elegans calcium channel gene we have begun to identify signaling partners associated with this calcium channel subtype by screening for novel gene mutations that restore the mutant strain’s ability to move normally or prevent convulsions.

Our investigations have thus far produced evidence suggesting the calcium channel acts as a neural activity dependent regulator of Insulin and TGF-beta signaling pathways that control the rate of synthesis of the migraine and epilepsy related neurotransmitter Serotonin. Interestingly, dysfunction in the human P/Q-type Ca2+ channel leads to unilateral head pain that responds to serotonergic receptor agonists, and loss of function mutations in the C. elegans P/Q-type Ca2+ channel gene leads to unilateral loss of serotonin production in a pair of neurons that help gauge the intensity of environmental stimuli. These findings provide novel insights that point to possible novel targets for therapeutic intervention that could be exploited in the future. Other projects currently underway include the genetic analysis of a C. elegans model of motor neuron diseases like amyotrophic lateral sclerosis and a C. elegans model of Abeta induced neurotoxicity in Alzheimer's disease.

Dr. Estevez's publications can be reviewed through the National Library of Medicine's publication database.

Board Certifications

Neurology

Hospital Privileges

Veterans Administration Hospital

Professional Organization Membership

American Academy of Neurology
Genetics Society of America
Society for Neuroscience