Neurodegeneration, Systems Biology, Bioinformatics, Transcriptomics, Epigenetics, Genetics, Alzheimer's disease, Therapeutics, Aging
American Federation of Aging Research (AFAR) Young Investigator Award
John Spice Award in Aging
The human brain changes at the molecular and cellular level with aging, and these molecular changes reflect either healthy or degenerative behavioral and cognitive function. Degeneration at the cognitive level, known as dementia, is seen in a large proportion of the American population and dementia associated with neurodegenerative diseases like Alzheimer’s disease (AD) exacts a large societal and financial burden. There is an immediate need to understand what leads to degeneration and develop novel therapies for dementia.
My long-term research interests lie in comprehensive understanding of the role of transcriptional and regulatory pathways in neurodegenerative diseases. The lab is focusing on studying the expression patterns of coding and non-coding genes during the progression of the disease. We then integrate the data with multiscale high dimensional data from proteomics, epigenomics and genomics to gain insights into the molecular mechanisms of neurodegenerative diseases like Alzheimer's disease (AD), Fronto-temporal dementia (FTD) and Progressive Supranuclear Palsy.
Our initial studies are focussing on the use of several mouse models of AD and FTD and generating transcriptional profiles of mRNA, long non-coding RNA (lincRNA) and microRNA (miRNA) using high-throughput RNA -sequencing as well as open-chromatin region using ATAC-seq. The goal is to use RNA sequencing information to quantify the abundance of gene products and their structures (isoforms) to discover differences using traditional differential expression methods and co-expression network analysis (using WGCNA). We are integrating information from post-mortem patient tissues and iPSCs derived cells with the transgenic mice data to delineate underlying common mechanisms. We employ statistical and computational deep-learning algorithms to unravel hidden biological relationships. We are using state-of the art single cell and single nuclear sequencing to profile brain cell-type heterogeneity and understand the changes happening in distinct cell-types. We will be using unbiased systems biology approaches to unravel novel regulators of neurodegeneration and are particularly interested in identifying key molecular targets so that effective therapeutics could be developed.
Selected Publications (more complete list at: https://www.ncbi.nlm.nih.gov/myncbi/1rO9tZA6LkMkr/bibliography/public/)
Swarup V, Hinz FI, Noguchi K, Toyoshiba H, Oda A, Hirai K, Kondou S, Rexach J, Sarkar A, Seyfried NT, Trojanowski JQ, Lah JJ, Levey AI, Geschwind DH Identification of evolutionarily conserved gene networks that mediate tau-induced neurodegenerative dementia, Accepted, Nature Medicine, 2018
Seyfried NT, Dammer EB, Swarup V, Nandakumar D, Duong DM, Yin L, Deng Q, Nguyen T, Hales CM, Wingo T, Glass J, Gearing M, Thambisetty M, Troncoso JC, Geschwind DH, Lah JJ, Levey AI. A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease. Cell Syst. 2017 Jan 25;4(1):60-72.e4. doi: 10.1016/j.cels.2016.11.006. Epub 2016 Dec 15. PubMed PMID: 27989508; PubMed Central PMCID: PMC5269514.
Parikshak NN**, Swarup V**, Belgard TG**, Irimia M, Ramaswami G, Gandal MJ, Hartl C, Leppa V, Ubieta LTU, Huang J, Lowe JK, Belncowe BJ, Horvath S, Geschwind DH (2016). Genome-wide changes in lncRNA, splicing and regional gene expression patterns in autism. Nature 540(7633):423-427. PMID: 27919067 **Authors contributed equally
Seyfried NT, Dammer EB, Swarup V, Nandakumar D, Duong DM, Luming Y, Qiudong D, Nguyen T, Chadwick HM, Wingo T, Glass J, Gearing M, Thambisetty M, Troncoso JC, Geschwind DH, Lah JJ, Levey AI (2016) A Multi-Network Approach Identifies Protein-specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease. Cell Systems, Dec 14. pii: S2405-4712(16)30370-2. PMID: 27989508
Swarup V, Geschwind DH (2013). Alzheimer's disease: From big data to mechanism. Nature. 500(7460): 34-5. PMID: 23883924
Swarup V**, Audet JN**, Phaneuf D, Kriz J, Julien JP (2012). Abnormal Regenerative Responses and Impaired Axonal Outgrowth after Nerve Crush in TDP-43 Transgenic Mouse Models of Amyotrophic Lateral Sclerosis. Journal of Neuroscience. 32(50): 18186-95. PMID: 23238732. **Authors contributed equally
Lalancette-Hebert M, Swarup V, Beaulieu JM, Bohacek I, Abdelhamid E, Weng YC, Sato S, Kriz J (2012). Galectin-3 is required for resident microglia activation and proliferation in response to ischemic injury. Journal of Neuroscience. 32(30): 10383-95. PMID: 22386271
Swarup V, Phaneuf D, Dupré N, Petri S, Strong M, Kriz J, Julien JP (2011). Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor ?B-mediated pathogenic pathways. Journal of Experimental Medicine. 208(12): 2429-47. PMID: 22084410
Swarup V, Phaneuf D, Bareil C, Robertson J, Rouleau GA, Kriz J, Julien JP (2011). Pathological hallmarks of amyotrophic lateral sclerosis/frontotemporal lobar degeneration in transgenic mice produced with TDP- 43 genomic fragments. Brain. 134(Pt 9): 2610-26. PMID: 21752789.
Swarup V, Julien JP. (2011) ALS pathogenesis: recent insights from genetics and mouse models Prog Neuropsychopharmacol Biol Psychiatry. 2011 Mar 30;35(2):363-9.
Ghosh, J, Swarup, V, Saxena, A, Das, S, Hazra, A, Paira, P, Banerjee, S, Mondal, N. B, Basu, A. (2008) Therapeutic effect of a novel anilidoquinoline derivative, 2-(2-methyl-quinoline-4ylamino)-N-(2-chlorophenyl)-acetamide, in Japanese encephalitis: correlation with in vitro neuroprotection. International journal of antimicrobial agents, 32, 349-354.
Swarup, V, Ghosh, J, Das, S and Basu, A. (2008) Tumor necrosis factor receptor-associated death domain mediated neuronal death contributes to the glial activation and subsequent neuroinflammation in Japanese encephalitis. Neurochemistry international, 52, 1310-1321.
Swarup, V, Ghosh, J, Mishra, M. K. and Basu, A. (2008) Novel strategy for treatment of Japanese encephalitis using arctigenin, a plant lignan. Journal of antimicrobial chemotherapy, 61, 679-688.
Swarup, V, Das, S, Ghosh S, Basu, A (2007) Tumor necrosis factor receptor-1-induced neuronal death by TRADD contributes to the pathogenesis of Japanese encephalitis. Journal of neurochemistry, 103, 771-783.
Swarup, V, Ghosh, J, Ghosh, S, Saxena, A and Basu, A. (2007) Antiviral and anti-inflammatory effects of rosmarinic acid in an experimental murine model of Japanese encephalitis. Antimicrobial agents and chemotherapy, 51, 3367-3370.
Swarup, V, Ghosh, J., Duseja, R., Ghosh, S. and Basu, A. (2007) Japanese encephalitis virus infection decrease endogenous IL-10 production: correlation with microglial activation and neuronal death. Neuroscience letters, 420, 144-149.
American federation of Aging Research
Adelson Medical Research Foundation
Interdepartmental Neuroscience Program
Mathematical and Computational Biology
Institute for Memory Impairments and Neurological Disorders