Udai Pandey, PhD

  • Associate Professor, Pediatrics

Phone

412-692-3192

E-mail

udai@pitt.edu

Education & Training

PhD, Sanjay Gandhi Postgraduate Inst of Medical Science (2005)

Campus Address

4401 Penn Ave., Children's Hospital of Pittsburgh

One-Line Research Description

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.

Representative Publications

Casci I, Krishnamurthy K, Kour S, Ramesh N, Anderson EA, Oliver S, Grant R, Gochenaur L, Patel K, Tripathy V, Marrone L, Sterneckert J, Gleixner A, Donnelly C, Ruepp MD, Pasinelli P, Pandey
UB. Muscleblind acts as a modifier of FUS toxicity by modulating stress granule dynamics and SMN localization. Nat Commun. 2019 Dec 6;10(1):5583

 

Mann JR, Gleixner AM, Gomes E, DeChellis-Marks MR, Needham PG. Hurtle B, Portz B, Mauna JC, Calder CB, Copley KE, Wills ZP, Pandey UB, Broadsky, Thathiah A, Shorter J and Donnelly CJ. RNA antagonizes 1 TDP-43 proteinopathy. Neuron 2019; 102; 1-9

 

Reinhardt L, Kordes S, Reinhardt P, Glatza M, Baumann M, Drexker H, Menninger S, Casci I, Zischinsky G, Eickhoff J, Marrone L, Janosch A, Adachi K, Stehling M, Anderson EA, Storch A, Hermann A, Bickle M, Pandey UB, Schöler HR, Nussbaumer P, Klebl B and Sterneckert JA. Dual inhibition of GSK3 and CDK5 efficiently protects motor neurons against dying back pathology in multiple subtypes of ALS. Stem Cell Reports, 2019 Vol. 12; 1–16

 

Marrone L, Drexler H, Wang J, Tripathi P, Distler T, Heisterkamp P, Maharana S, Anderson EN, Kour S, Bhatnagar R, Belgard TG, Tripathy V, Moraiti A, Crippa V, Poletti A, Aronica E, Weis J, Pandey UB, Alberti S, Goswami A and Sterneckert J. FUS pathology in ALS is linked to alterations in multiple ALS-associated proteins and rescued by drugs stimulating autophagy. Acta Neuropathol. 2019 Jul;138(1):67-84

 

Anderson A, Gochenaur L, Singh A, Grant R, Patel K, Watkins S, Wu J, Pandey UB. Traumatic injury induces Stress Granule Formation and enhances Motor Dysfunctions in ALS Models. Hum Mol Genet. 2018 Apr 15; 27(8):1366-1381.

 

Bakthavachalu B, Huelsmeier J, Sudhakaran I, Hillebrand J, Singh A, Petrauskas A, Thiagarajan D, Sankaranarayanan M, Mizoe L, Anderson EA, Pandey UB, Ross E, VijayRaghavan K, Parker R, Ramaswami M. RNP-granules assembly via Ataxin02 disordered domains is required for long-term memory and neurodegeneration. Neuron. 2018 May 16; 98(4):754-766    *Previewed in ‘Neuron’

 

Guo L, Kim HJ, Wang H, Monaghan J, Freyermuth F, Sung JC, O'Donovan K, Fare CM, Diaz Z, Singh N, Zhang ZC, Coughlin M, Sweeny EA, DeSantis ME, Jackrel ME, Rodell CB, Burdick JA, King OD, Gitler AD, Lagier-Tourenne C, Pandey UB, Chook YM, Taylor JP, Shorter J. Nuclear-Import Receptors Reverse Aberrant Phase Transitions of RNA-Binding Proteins with Prion-like Domains. Cell. 2018 Apr19; 173(3):677-692

 

Marrone L, Japtok J, Reinhardt P, Janosch A, Andree A, Lee H, Moebius C, Reinhardt L, Hackmann K, Klink B, Alberti S, Bickle M, Hyman AA, Casci I, Pandey UB, Hermann A, and Sterneckert J. Phenotypic screening using iPSC reporter lines identifies brain-penetrant drugs stimulating autophagy as therapeutics for FUS-ALS. Stem Cell Reports. 2018 Feb 13; 10(2):375-389.

 

Kim SH, Stiles SG, Feichtmeier JM, Ramesh N, Zhan L, Scalf MA, Smith LM, Pandey UB, Tibbetts RS. Mutation-dependent aggregation and toxicity in a Drosophila model for UBQLN2-associated ALS. Hum Mol Genet. 2018 Jan 15; 27(2):322-337

 

Rudich P, Snoznik C, Watkins SC, Monaghan J, Pandey UB, Lamitina T. Nuclear localized C9orf72 associated arginine containing dipeptides exhibit age-dependent toxicity in C. elegans. Hum Mol Genet. 2017 Dec 15; 26(24):4916-4928

 

Ramesh N, Pandey UB, Proteostasis dysfunction in ALS: Autophagy eating its way to prominence. Front Mol Neurosci. 2017 Aug 22; 10:263

 

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.