Pedro Gonzalez-Alegre, M.D. (Associate Member)
Assistant Professor, Department of Neurology, University of Iowa

http://www.uihealthcare.com/depts/med/neurology/neurologymds/gonzalez.html

Research Interest    

The major goal of the Gonzalez-Alegre laboratory is to understand the biological basis of disorders caused by dysfunction of the basal ganglia and use that knowledge to develop novel therapies for this group of neurological diseases. Currently, studies in my lab focus on a disease known as DYT1 dystonia, the most common form of inherited dystonia. DYT1 dystonia, a dominantly inherited, incurable disease, is caused by a three-nucleotide deletion in the gene TOR1A that causes the loss of a glutamic acid in the protein torsinA. TorsinA is a AAA protein (ATPases Associated with diverse cellular Activities) that resides primarily in the endoplasmic reticulum. However, our lab and others demonstrated that torsinA carrying the disease-causing mutation accumulates abnormally in the nuclear envelope. Over the next few years, my laboratory will focus on DYT1 dystonia research through the following major projects: 1) Define the biological role of torsinA and its role in DYT1 pathogenesis; 2) Understand how the neuronal protein quality control machinery ?handles? torsinA and the significance of this process in disease pathogenesis; 3) Development of therapeutic RNAi interference for DYT1 dystonia. In addition to enhancing our knowledge on the pathogenesis of dystonia and related disorders, these studies will contribute to exploit RNA interference as a therapy for DYT1 and other incurable neurological diseases.

Selected Publications:

Gonzalez-Alegre P, Miller VM, Davidson B, Paulson H. Toward therapy for DYT1 dystonia: Allele-specific silencing of mutant torsinA. Ann Neurol 2003;53:781-787.

Gonzalez-Alegre P, Paulson HL. Aberrant cellular behavior of mutant TorsinA implicates nuclear envelope dysfunction in DYT1 dystonia. J Neuroscience 2004;24(11):2593-2601.

Gonzalez-Alegre P, Bode N, Davidson BL, Paulson HP. Silencing primary dystonia: lentiviral-mediated RNA interference therapy for DYT1. J Neuroscience 2005;25: 10502-10509.

Miller VM, Paulson HL, Gonzalez-Alegre P. RNA interference in neuroscience: progress and challenges. Cellular and Molecular Neurobiology 2005;25(8):1195-1207.

Rodriguez-Lebron E, Gonzalez-Alegre P. Silencing neurodegenerative disease: bringing RNA interference to the clinic. Expert Review of Neurotherapeutics 2006;6(2):223-233.

Gonzalez-Alegre P. Therapeutic RNA interference for neurodegenerative diseases: from promise to progress. Pharmacol Ther 2007;114(1):34-55.

Gonzalez-Alegre P. The inherited dystonias. Semin Neurol 2007;27(2):151-8.

Gonzalez-Alegre P, Paulson HP. Technology insight: therapeutic RNA interference--how far from the neurology clinic? Nat Clin Pract Neurol 2007;3(7):394-404.

Gordon KL, Gonzalez-Alegre P. Consequences of the DYT1 mutation on torsinA oligomerization and degradation. Neuroscience 2008; 157:588-595.

Martin JN, Bair TB, Bode N, Dauer WT, Gonzalez-Alegre P. Transcriptional and proteomic profiling in a cellular model of DYT1 dystonia. Neuroscience 2009 (in press)

Publications from PubMed