Udai Pandey, PhD

  • Associate Professor of Pediatrics, Human Genetics & Neurology

    Education & Training

  • Graduate School - Sanjay Gandhi Postgraduate Institute of Medical Sciences, India – PhD – Medical Genetics
  • Post-Doctoral Fellowship – University of Pennsylvania – Neurology
  • Post-Doctoral Fellowship – St. Jude Children’s Research Hospital – Developmental Neurobiology
Research Grants

NIH Grants:  R21, R01

Research Summary

Dr. Pandey’s laboratory is interested in understanding the molecular mechanisms of human neurological diseases such as amyotrophic lateral sclerosis (ALS) and traumatic brain injury. We have been using mammalian neuronal cells, Drosophila and patient-derived iPSC lines to examine the contribution of pathogenic mutations that lead to ALS pathogenesis. Several RNA-binding proteins have been implicated in human neurodegenerative diseases, such as polyglutamine expansion diseases and ALS. TDP-43, FUS, Matrin-3, VCP, and other RNA-binding proteins have been linked to ALS and suggest that defective RNA metabolism is central to ALS pathogenesis. The Pandey lab developed cellular and Drosophila models of ALS by expressing human and fly versions of disease-causing genes that regulate RNA metabolism. These models recapitulate several key features of the human disease, including neuromuscular junction defects, cytoplasmic accumulation of mutant protein, and behavioral defects. The Pandey lab is now performing genetic and small molecule screens to identify modifiers of neurodegenerative phenotypes in vivo. Discovery of these modifiers will enhance our understanding of mechanisms of ALS and will help in identifying new pathways for therapeutic drug development. The Pandey lab provides an exciting environment for training the next generation of physician-scientists and scientists interested in studying the molecular pathogenesis of human neurodegenerative diseases.

Representative Publications
  1. 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. Nature Communications (In Press)
  2. 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
  3. 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
  4. 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.
  5. 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’
  6. 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
  7. 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.
  8. 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
  9. 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):4916-492
  10. Ramesh N, Pandey UB, Proteostasis dysfunction in ALS: Autophagy eating its way to prominence. Front Mol Neurosci. 2017 Aug 22; 10:263
  11. 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.