Gene identification and molecular mechanisms underlying neurodegenerative and demyelinating disorders
The major focus of the Padiath lab is to understand the molecular mechanisms underlying various neurological diseases with an emphasis on disorders of myelin that are known as leukodystrophies. This work involves the use of clinical based population and family studies to identify disease causing genes and the development of animal and cell culture models to elucidate disease mechanisms.
Presently, we are studying the genetic basis of the adult onset demyelinating disorder, Autosomal Dominant Leukodystrophy (ADLD). We have previously shown that ADLD is caused by duplications of the nuclear lamina protein, Lamin B1. Using mouse, fly and cell culture models we have generated, we aim to understand how Lamin B1, a nuclear structural protein that is ubiquitously expressed, regulates a distinct process such as myelination.
We hope that by studying mechanisms of demyelinating diseases such as ADLD, we will discover novel pathways that regulate myelin formation and maintenance. These pathways can help identify therapeutic targets that may have relevance not only for the treatment of leukodystrophies but also for common demyelinating diseases such as Multiple Sclerosis.
Harshvardhan Rolyan, Yulia Y. Tyurina, Marylens Hernandez, Andrew A. Amoscato, Loius J. Sparvero, Bruce S. Nmezi, Yue Lu, Marcos R. H. Estécio, Kevin Lin, Junda Chen, Rong-Rong He, Pin Gong, Lora H. Rigatti, Jeffrey Dupree, Hülya Bayir, Valerian E. Kagan, Patrizia Casaccia, Quasar S. Padiath. Defects of lipid synthesis are linked to the age dependent demyelination caused by Lamin B1 over expression. J. Neurosci (in press).
Amy Pizzino, Tyler Pierson, Yiran Guo, Guy Helman, Sebastian Fortini, Kether Guerrero, Sulagna Saitta, Jennifer Murphy, Quasar Padiath, Yi Xie, Hakon Hakonarson, Jun Wang, Tara Funari, Michelle Fox, Ryan Taft, Marjo S. van der Knaap, Genevieve Bernard, Raphael Schiffmann, Cas Simons, Adeline Vanderver TUBB4A de novo mutations cause isolated hypomyelination. 2014;83(10):898-902.Neurology.
Elisa Giorgio#, Harshvardhan Rolyan#, Laura Kropp, Anish B Chakka, Svetlana Yatsenko, Eleonora Di Gregorio, Daniela Lacerenza, Giovanna Vaula, Flavia Talarico, Paola Mandich, Camilo Toro, Eleonore E Pierre, Pierre Labauge, Sabina Capellari, Pietro Cortelli, Filippo P Vairo, Diego Miguel, Danielle Stubbolo, Lourenco C Marques, William Gahl, Odile Boespflug-Tanguy, Atle Melberg, Sharon Hassin-Baer, Oren S Cohen, Rastislav Pjontek, Armin Grau, Thomas Klopstock, Brent Fogel, Inge Meijer, Guy Rouleau, Jean-Pierre L Bouchard, Madhavi Ganapathiraju, Adeline Vanderver, Niklas Dahl, Grace Hobson, Alfredo Brusco, Alessandro Brussino, Padiath QS Analysis of LMNB1 Duplications in Autosomal Dominant Leukodystrophy Provides Insights into Duplication Mechanisms and Allele Specific Expression Levels. Human Mutation 2013;34(8):1160-71.
Padiath, Q.S., Saigoh, K., Schiffmann, R., Asahara, H., Yamada, T., Koeppen, A., Hogan, K., Ptacek, L.J. & Fu, Y.H. Lamin B1 duplications cause autosomal dominant leukodystrophy. Nat Genet 38, 1114-23 (2006).
Xu, Y*., Padiath, Q.S*., Shapiro, R.E., Jones, C.R., Wu, S.C., Saigoh, N., Saigoh, K., Ptacek, L.J. & Fu, Y.H. Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome. Nature 434, 640-4 (2005). *- Equal Contribution