Opal, Puneet, MD, PhD
Ward 10-332 Chicago
|Areas of Research||
Cell Biology, Molecular Neuroscience, Motor Control, Neurobiology of Disease
|NU Scholar Profile|
|Recent Publications on PubMed|
The long-term goal of my laboratory is to understand the cellular basis of neurodegeneration. We are testing the idea that neurodegeneration results from derangements in relatively few but strategic sub-cellular pathways. By identifying critical components of these pathways one could begin to not only understand the biology of neurodegeneration, but also embark on the design of novel therapeutic agents.
We are currently studying the autosomal dominant disorder Spinocerebellar Ataxia Type 1 (SCA1), a relentless disease that affects cerebellar Purkinje cells and brainstem neurons. This disorder is caused by a polyglutamine expansion in the involved disease protein and is thus similar to a growing number of disorders, including Huntington disease, that share this mutational mechanism. Patients with SCA1 begin to display cerebellar signs characterized by motor incoordination or ataxia in early to mid adulthood. Unfortunately there is no treatment for this disease and patients eventually succumb from the complications of brainstem dysfunction.
Testing the transcriptional hypothesis in SCA1 pathogenesis:
Testing the role of the vascular and angiogenic factor VEGF in SCA1 pathogenesis.
Testing the role of ataxin-1 misfolding and clearance in disease pathogenesis.
In addition to spinocerebellar ataxia, we are also studying genetic parkinsonian and dystonic syndromes.
VEGF ameliorates the ataxic phenotype in spinocerebellar ataxia type 1 (SCA1) mice. Cvetanovic, M., Patel, P., Marti, H.H., Kini A.R., and Opal, P. Nature Medicine. 17(11):1445-7 (2011).
Kular R.K., Gogliotti, R.G., and Opal, P. CPD-1 null mice display a subtle neurological phenotype. PLoS One 5(9). pii: e12649 (2010).
Kular R.K., Cvetanovic M., Siferd S., Kini A.R., Opal, P. Neuronal Differentiation Is Regulated by Leucine-rich Acidic Nuclear Protein (LANP), a Member of the Inhibitor of Histone Acetyltransferase Complex. Journal of Biological Chemistry 284(12):7783-7792 (2009).
Paganoni, S., Seelaus, C.A., Ormond, K.E., Opal, P. Association of Spinocerebellar ataxia type 3 (SCA3) and Spinocerebellar ataxia type 8 (SCA8) microsatellite expansions. Movement Disorders 1, 154-155 (2008).
Bassuk, A.G., Chen, Y.Z., Batish, S.D., Nagan, N., Opal, P., Chance, P.F., and Bennett, C.L. In cis autosomal dominant mutation of Senataxin associated with tremor/ataxia syndrome. Neurogenetics 8, 45-49 (2007).
Cvetanovic, M., Rooney, R.J., Garcia, J.J., Toporovskaya, N., Zoghbi, H.Y., and Opal, P. The role of LANP and ataxin-1 in E4F-mediated transcriptional repression. EMBO Reports 8, 671-677 (2007).
Paganoni, S., Naidech, A.M., and Opal, P. Huntington’s disease presenting as post-surgical psychosis. Movement Disorders 22, 1209-1210 (2007).
Opal, P., Garcia, J.J., McCall, A., Xu, B., Weeber, E.J., Sweatt, J.D., Orr, H.T., and Zoghbi, H.Y. Generation and characterization of LANP/pp32 null mice. Molecular and Cellular Biology 8, 3140-9 (2004).
Opal, P., Garcia, J.J., Propst, F., Matilla, A., Orr, H.T. and Zoghbi, H. Mapmodulin/LANP binds the light chain of microtubule associated protein 1B and modulates neuritogenesis. Journal of Biological Chemistry, 278, 34691-9 (2003).
Opal, P. and Zoghbi, H.Y. The role of chaperones in polyglutamine disease. Trends in molecular medicine 8, 232-236 (2002).
Opal, P., Tintner, R., Jankovic, J., Leung, J., Breakefield, X.O., Friedman, J and Ozelius, L. Intrafamilial phenotypic variability of the DYT1 dystonia. From asymptomatic TOR1A gene carrier status to dystonic storm. Movement Disorders 17, 339-342 (2002).
Cummings, C.J, Sun, Y., Opal, P., Antalffy, B, Mestril, R., Orr, H.T., Dillman, W.H. and Zoghbi, H.Y. Overexpression of inducible HSP70 chaperone suppresses neuropathology and involves motor function in SCA1 mice. Human Molecular Genetics 10, 1511-1518 (2001).