Gender	Female
E-mail	laurie.ozelius@mssm.edu
Education and Training	Ph.D, Harvard Medical School
	Sc.B, Brown University

E-mail: laurie.ozelius@mssm.edu
Tel: (212) 659-6753
Fax: (212) 849-2508
Mailing Address:
One Gustave L. Levy Place, Box 1498, New York, NY 10029
Location:
Icahn Medical Institute, 1425 Madison Avenue, Rm. 14-20B

Education and Training	Ph.D, Harvard Medical School
	Sc.B, Brown University

Specific Clinical/Research Interests: Genetics of Movement Disorders, Parkinson's Disease, Dystonia, Basal Ganglia, Brain, Linkage Analysis, Association Studies, Pentrance, Haplotype, Molecular Biology

Summary of Research Studies
My lab is focused on finding genes involved in movement disorders, particularly hereditary dystonia and Parkinson's disease (PD). Dystonia is characterized by involuntary twisting and repetitive movements due to loss of motor control in different body parts. Hereditary cases do not appear to have any associated neuropathology, but secondary dystonias implicate dysfunction of the basal ganglia in the brain. There are several clinically and genetically distinct subtypes of hereditary dystonia, most of which are inherited as autosomal dominant traits with reduced penetrance (i.e. individuals can carry the disease gene but not express the trait), resulting from over 15 different genes. 

We identified a gene (DYT1) for the early onset form of dystonia and are generating various mouse models for this disease. In addition, we are interested in finding genes that influence the penetrance of this disorder. We have identified mutations in the epsilon sarcoglycan for myoclonus-dystonia and are pursuing genotype:phenotype correlations and functional studies. We also identified the ATP1A3 gene on chromosome 19 as being mutated in rapid onset dystonia parkinsonism and are beginning initial characterization. We are working with a large Mennonite family linked to the DYT6 locus on chromosome 8 with positional cloning and mutational analysis ongoing in this region. Finally, we are performing genome scans in several large families with later onset dystonia and pursing candidate gene and whole genome association studies in focal dystonia patients to find genes and susceptibility loci for these disorders.

Most recently, the lab has started to work on identifying genes involved in PD. The cardinal symptoms associated with PD include rigidity, postural instability, bradykinesia and tremor and the disease is characterized by neurodegeneration of the dopaminergic neurons in the basal ganglia. PD is a complex disease with both genes and environmental factors contributing to disease. To reduce the heterogeneity associated with PD, we are looking for genes in an isolated population concentrating on PD patients of Ashkenazi Jewish (AJ) descent. We identified a founder mutation in the LRRK2 gene that is responsible for 18% of PD among AJs and estimated the penetrance to be only 35%. We are following up these studies by collecting family members that can be used to identify genes influencing penetrance. We are also looking at populations to try and determine the age and origin of the founder mutation and are pursuing whole genome association studies on the other 70% of AJ PD patients to identify other genes involved in their disease.

Identification and the subsequent characterization of the various genes causing dystonia and PD will clarify the underlying mechanisms and the basic pathophysiology of these disorders, and provide the basis for more effective treatments. 

Raymond D, Saunders-Pullman R, de Carvalho Aguiar P, Schule B, Kock N, Friedman J, Harris J, Ford B, Frucht S, Heiman GA, Jennings D, Doheny D, Brin MF, de Leon Brin D, Multhaupt-Buell T, Lang AE, Kurlan R, Klein C, Ozelius L, Bressman S. Phenotypic spectrum and sex effects in eleven myoclonus-dystonia families with epsilon-sarcoglycan mutations. Mov Disord 2008 Mar 15; 23(4): 588-592.

Holtzer R, Ozelius L, Xue X, Wang T, Lipton RB, Verghese J. Differential effects of COMT on gait and executive control in aging [Epub ahead of print]. Neurobiol Aging 2008 Jun 9;.

Risch NJ, Bressman SB, Senthil G, Ozelius LJ. Intragenic Cis and Trans modification of genetic susceptibility in DYT1 torsion dystonia. Am J Hum Genet 2007 Jun; 80(6): 1188-1193.

Brashear A, Ozelius LJ, de Carvalho Aguiar P, Borg M, Frijns CJ, Gollamudi S, Green A, Guimaraes J, Haake BC, Klein C, Linazasoro G, Munchau A, Raymond D, Riley D, Saunders-Pullman R, Tijssen MA, Webb D, Zaremba J, Bressman SB, Dobyns WB. The phenotypic spectrum of rapid-onset dystonia-parkinsonism (RDP) and mutations in the ATP1A3 gene. Brain 2007 Mar; 130(Pt 3): 828-835.

Saunders-Pullman R, Raymond D, Senthil G, Kramer P, Ohmann E, Deligtisch A, Shanker V, Greene P, Tabamo R, Huang N, Tagliati M, Kavanagh P, Soto-Valencia J, Aguiar Pde C, Risch N, Ozelius L, Bressman S. Narrowing the DYT6 dystonia region and evidence for locus heterogeneity in the Amish-Mennonites. Am J Med Genet A 2007 Sep 15; 143A: 2098-2105.

Borges V, Aguiar PD, Ferraz HB, Ozelius LJ. Novel and de novo mutations of the SGCE gene in Brazilian patients with myoclonus-dystonia. Mov Disord 2007; 22: 1208-1209.

Ozelius LJ, Foroud T, May S, Senthil G, Sandroni P, Low PA, Reich S, Colcher A, Stern MB, Ondo WG, Jankovic J, Huang N, Tanner CM, Novak P, Gilman S, Marshall FJ, Wooten GF, Chelimsky TC, Shults CW. G2019S mutation in the leucine-rich repeat kinase 2 gene is not associated with multiple system atrophy. Mov Disord 2007; 22: 546-549.

Ozelius LJ, Senthil G, Saunders-Pullman R, Ohmann , Deligtisch A, Tagliati M, Bressman SB, Klein C, Henick B, Hailpern SM, Lipton RB, Soto-Valencia J, Risch N, Hunt AL. LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews. NEJM 2006; 354: 424-425.

de Carvalho Aguiar P, Sweadner KJ, Penniston J, Zaremba J, Tijssen MJ, Caton M, Linazasoro G, Borg M, Liu L. Mutations in the NA+K+ -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. Neuron 2004; 43(2): 169-175.

Ozelius LJ, Breakefield XO, Page C, Bressman SB, Kramer P, Shalish C, de Leon D, Brin MF, Raymond D, Corey DP, Fahn S, Risch N, Buckler AJ, Gusella JF, Hewett J. The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein. Nature Genetics 1997; 17: 40-48.