Molecular mechanisms of human neurodegenerative diseases
The main focus of Pandey laboratory is to elucidate the molecular mechanisms of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, and other related motor neurons diseases. Recently, several RNA-binding proteins have been found to be mutated in both sporadic and familial forms of ALS. Disease causing mutations in these RNA binding proteins suggest that underlying defects in RNA metabolism might play an important role in causing motor neuron degeneration in ALS. The Pandey lab developed fly models of ALS that recapitulate several key pathological features of human disease such as neurodegeneration and behavioral defects. He has been utilizing cell biological, genetic and biochemical techniques to understand molecular mechanisms of ALS in drosophila and mammalian neuronal models. The Pandey lab is looking for genetic and small molecule modifiers of ALS in fly and mammalian neuronal models. We expect that these modifiers will not only allow us to understand molecular basis of ALS but also help in developing therapeutic interventions for ALS.
Daigle JG, Krishnamurthy K, Ramesh R, Casci I, Monaghan J, McAvoy K, Godfrey GW, Daniel D, Johnson E, Monahan Z, Shewmaker F, Pasinelli P, Pandey UB. Pur alpha ameliorates FUS toxicity and regulates cytoplasmic stress granule dynamics. Acta Neuropathologica 2016 Jan 4
Scaramuzzino C, Casci I, Parodi S, Lievens PMJ, Milioto C, Polanco MJ, Chivet M, Mishra A, Badders N, Aggarwal N, Grunseich C, Sambataro F, Basso M, Fackelmayer FO, Taylor JP, Pandey UB and Pennuto M. Protein arginine methyltransferase 6 enhances polyglutamine-expanded androgen receptor function and toxicity in spinal and bulbar muscular atrophy. Neuron 2015 Jan 7; 84(7)
Wen X, Tan W, Westergard T, Krishnamurthy K, Shamamandri Markandaiah S, Lin S, Ichida JK, Monaghan J, Pandey UB, Pasinelli P and Trotti D. Antisense Proline-Arginine RAN dipeptides linked to C9ORF72-ALS/FTD form toxic nuclear aggregates that initiate in vitro and in vivo neuronal death, Neuron 2014 Dec 17;84(6)
Shahidullah M, Le Marchand SJ, Fei H, Zhang J, Pandey UB, Dalva MB, Pasinelli P, Levitan IB. Defects in Synapse Structure and Function Precede Motor Neuron Degeneration in Drosophila Models of FUS-Related ALS. J Neurosci. 2013 Dec 11;33(50):19590-8
Daigle JG, Lanson NA, Smith RB, Casci I, Maltare A, Monaghan J, Nichols CD, Kryndushkin D, Shewmaker F, Pandey UB. RNA binding ability of FUS regulates neurodegeneration, cytoplasmic mislocalization and incorporation into stress granules associated with FUS carrying ALS-linked mutations. Human Molecular Genetics 2013 Mar 15;22(6):1193-205.
Lanson NA, Maltare A, King H, Smith R, Kim JH, Taylor JP, Lloyd TE and Pandey UB. A Drosophila model of FUS-related neurodegeneration reveals genetic interaction between FUS and TDP-43. Human Molecular Genetics 2011 Jul 1;20(13):2510-23.
Pandey UB, Nie Z, Batlevi Y, McCray BA, Ritson GP, Nedelsky NB, Schwartz SL, DiProspero NA, Knight MA, Schuldiner O, Padmanabhan R, Hild M, Berry DL, Garza D, Hubbert CC, Yao TP, Baehrecke EH, Taylor JP. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature. 2007 Jun 14; 447(7146):860-4. *Previewed in Neuron and selected for ‘must read paper’ by faculty 1000 biology.
View Dr. Pandey’s full list of publications from Pubmed