Quasar S. Padiath, PhD

  • Associate Professor, Human Genetics

Phone

412-624-7203

E-mail

qpadiath@pitt.edu

Education & Training

PhD, Indian Institute of Science, Bangalore, India (2001)

Location

4060G Parran Hall Lab Annex

Research Interest Summary

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.

Viviana Lo Martire, Sara Alvente, Stefano Bastianini, Chiara Berteotti, Cristiano Bombardi, Giovanna Calandra-Buonaura, Sabina Capellari, Gary Cohen, Pietro Cortelli, Laura Gasparini, Quasar Padiath, Alice Valli, Giovanna Zoccoli, Alessandro Silvani, Mice overexpressing lamin B1 in oligodendrocytes recapitulate the age-dependent motor signs, but not the early autonomic cardiovascular dysfunction of autosomal-dominant leukodystrophy (ADLD), Experimental Neurology, Volume 301, Part A, 2018, Pages 1-12, ISSN 0014-4886, https://doi.org/10.1016/j.expneurol.2017.12.006.

 

Padiath, Quasar S. “Autosomal Dominant Leukodystrophy: A Disease of the Nuclear Lamina.” Frontiers in Cell and Developmental Biology, vol. 7, 2019, doi:10.3389/fcell.2019.00041.


Concentric organization of A- and B-type lamins predicts their distinct roles in the spatial organization and stability of the nuclear lamina Bruce Nmezi, Jianquan Xu, Rao Fu, Travis J. Armiger, Guillermo Rodriguez-Bey, Juliana S. Powell, Hongqiang Ma, Mara Sullivan, Yiping Tu, Natalie Y. Chen, Stephen G. Young, Donna B. Stolz, Kris Noel Dahl, Yang Liu, Quasar S. Padiath Proceedings of the National Academy of Sciences Mar 2019, 116 (10) 4307-4315; DOI: 10.1073/pnas.1810070116


Genomic deletions upstream of lamin B1 lead to atypical autosomal dominant leukodystrophy Bruce Nmezi, Elisa Giorgio, Raili Raininko, Anna Lehman, Malte Spielmann, Mary Kay Koenig, Rahmat Adejumo, Melissa Knight, Ralitza Gavrilova, Murad Alturkustani, Manas Sharma, Robert Hammond, William A. Gahl, Camilo Toro, Alfredo Brusco, Quasar S. Padiath
Neurol Genet Feb 2019, 5 (1) e305; DOI: 10.1212/NXG.0000000000000305
 

Natural History of Vanishing White Matter. Hamilton EMC, van der Lei HDW, Vermeulen G, Gerver JAM, Lourenço CM, Naidu S, Mierzewska H, Gemke RJBJ, de Vet HCW, Uitdehaag BMJ, Lissenberg-Witte BI; VWM Research Group, van der Knaap MS. Ann Neurol. 2018 Aug;84(2):274-288. doi: 10.1002/ana.25287. Epub 2018 Sep 6.PMID 30014503

 

Rolyan, R, Tyurina, YY, Hernandez, H, Amoscato, AA, Sparvero, LJ, Nmezi, BS, Lu, Y Estécio, MRH, Lin, K, Chen, J, He, R, Gong, R Rigatti, LH, Dupree,J, Bayir, H, Kagan,VE, Casaccia, P, Padiath,QS. Defects of lipid synthesis underlie the age dependent demyelination caused by lamin B1 over expression. J Neurosci, (2015), 35(34):12002-12017.

 

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

 

Link to more publications: 

https://www.ncbi.nlm.nih.gov/sites/myncbi/14SZefWFJoeQV/bibliography/479...