Ranjan  Dutta,  Ph.D.

Ranjan Dutta, Ph.D.

Assistant Staff

Assistant Professor, Molecular Medicine, CCLCM-CWRU

Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195


Significant progress have been made in understanding the relapse-remitting phase of multiple sclerosis (MS). Less progress has been made, however, in deciphering the progressive phase of the diseae. Development of therapeutic strategies will require understanding the pathogenesis of this progressive phase. It is now accepted that demyelination and associated neuronal and axonal degeneration are responsible for the irreversible neurological disability that most MS patients endure. Our research uses postmortem tissues derived from MS brains, animal models of MS, and genomic tools to unravel mechanisms underlying demyelination, remyelination, and axonal and neuronal loss in MS. We usually start with finding clues from MS brain tissues and then trying to mimic these changes in animal models and in vitro experiments.

Lay Summary

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and is the major cause of atraumatic neurological disability in young adults in North America and Europe.  Although existing therapeutic options are helpful during the initial relapse-remitting phase of MS, there are few available options for the progressive phase of the disease.  Our research is primarily directed towards understanding the molecular changes underlying the progressive neurological disability experienced by MS patients.

Selected Publications:

Rai NK, Singh V, Li L, Willard B, Tripathi A, Dutta R. (2021) Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains. Front Neurol. 12:779003. PMID: 35002930; PMCID: PMC8740228

Baltan S, Sandau US, Brunet S, Bastian C, Tripathi A, Nguyen H, Liu H, Saugstad JA, Zarnegarnia Y, Dutta R. (2021) Identification of miRNAs That Mediate Protective Functions of Anti-Cancer Drugs During White Matter Ischemic Injury. ASN Neuro. 13:17590914211042220. PMID: 34619990; PMCID: PMC8642107

Tripathi A, Pandit I, Perles A, Zhou Y, Cheng F, Dutta R. (2021) Identifying miRNAs in multiple sclerosis gray matter lesions that correlate with atrophy measures. Ann Clin Transl Neurol. 8(6):1279-1291. PMID: 33978322; PMCID: PMC8164853

Baltan S, Jawaid SS, Chomyk AM, Kidd GJ, Chen J, Battapady HD, Chan R, Dutta R, Trapp BD. (2021) Neuronal hibernation following hippocampal demyelination. Acta Neuropathol Commun. 9(1):34. PMID: 33648591; PMCID: PMC7923530

Factor DC, Barbeau AM, Allan KC, Hu LR, Madhavan M, Hoang AT, Hazel KEA, Hall PA, Nisraiyya S, Najm FJ, Miller TE, Nevin ZS, Karl RT, Lima BR, Song Y, Sibert AG, Dhillon GK, Volsko C, Bartels CF, Adams DJ, Dutta R, Gallagher MD, Phu W, Kozlenkov A, Dracheva S, Scacheri PC, Tesar PJ, Corradin O. (2020) Cell Type-Specific Intralocus Interactions Reveal Oligodendrocyte Mechanisms in MS. Cell 181(2):382-395.e21. PMID: 32246942

Bhargava P, Smith MD, Mische L, Harrington EP, Fitzgerald KC, Martin KA, Kim S, Reyes AAA, Gonzalez-Cardona J, Volsko C, Tripathi A, Singh S, Varanasi K, Lord HN, Meyers KR, Taylor M, Gharagozloo M, Sotirchos ES, Nourbakhsh B, Dutta R, Mowry E, Waubant E, Calabresi PA. (2020)Bile acid metabolism is altered in multiple sclerosis and supplementation ameliorates neuroinflammation. J Clin Invest. 130(7):3467-3482. PMID: 32182223

Sarn N, Jaini R, Thacker S, Lee H, Dutta R, Eng C. (2020) Cytoplasmic-predominant Pten increases microglial activation and synaptic pruning in a murine model with autism-like phenotype. Mol Psychiatry. 2020 Feb 13.PMID: 32055008

Tripathi A, Volsko C, Garcia JP, Agirre E, Allan KC, Tesar PJ, Trapp BD, Castelo-Branco G, Sim FJ, Dutta R. (2019) Oligodendrocyte Intrinsic miR-27a Controls Myelination and Remyelination. Cell Rep. 29(4):904-919.e9. PMID: 31644912; PMCID: PMC6874400

Dutta R, Mahajan KR, Nakamura K, Ontaneda D, Chen J, Volsko C, Dudman J, Christie E, Dunham J, Fox RJ, Trapp BD. (2019) Comprehensive Autopsy Program for Individuals with Multiple Sclerosis. J Vis Exp. 2019 Jul 19;(149). PMID: 31380830

Kirby L, Jin J, Cardona JG, Smith MD, Martin KA, Wang J, Strasburger H, Herbst L, Alexis M, Karnell J, Davidson T, Dutta R, Goverman J, Bergles D, Calabresi PA. (2019) Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination. Nat Commun. 10(1):3887. PMID: 31467299; PMCID: PMC6715717

Kremer D, Gruchot J, Weyers V, Oldemeier L, Göttle P, Healy L, Ho Jang J, Kang T Xu Y, Volsko C, Dutta R, Trapp BD, Perron H, Hartung HP, Küry P. (2019) pHERV-W envelope protein fuels microglial cell-dependent damage of myelinated axons in multiple sclerosis. Proc Natl Acad Sci USA. 116(30):15216-15225. PMID: 31213545; PMCID: PMC6660731

Singh V, Tripathi A, Dutta R. (2019) Proteomic Approaches to Decipher Mechanisms Underlying Pathogenesis in Multiple Sclerosis Patients. Proteomics. 19(16):e1800335. PMID: 31119864; PMCID: PMC6690771

Tripathi A, Volsko C, Datta U, Regev K, Dutta R. (2019) Expression of disease-related miRNAs in white-matter lesions of progressive multiple sclerosis brains. Ann Clin Transl Neurol. 6(5):854-862. PMID: 31139683; PMCID: PMC6530016

Lee H, Thacker S, Sarn N, Dutta R, Eng C. (2019) Constitutional mislocalization of Pten drives precocious maturation in oligodendrocytes and aberrant myelination in model of autism spectrum disorder. Transl Psychiatry. (9) 13-25. PMID: 30664625; PMCID: PMC6341090

Kremer D, Akkermann R, Küry P, Dutta R. (2018) Current advancements in promoting remyelination in multiple sclerosis. Mult Scler. (25) 7-14. PMID: 30270725; PMCID: PMC6389436

Bastian C, Quinn J, Tripathi A, Aquila D, McCray A, Dutta R, Baltan S, Brunet S. (2018) CK2 inhibition confers functional protection to young and aging axons against ischemia by differentially regulating the CDK5 and AKT signaling pathways. Neurobiol Dis. (18)30149-9. PMID: 29944965

Savarin C, Dutta R, Bergmann CC. (2018) Distinct Gene Profiles of Bone Marrow-Derived Macrophages and Microglia During Neurotropic Coronavirus-Induced Demyelination. Front Immunol. 9:1325. PMID: 29942315; PMCID: PMC6004766

Dutta R, Trapp BD. (2018) Much, if not all, of the cortical damage in MS can be attributed to the microglial cell - No. Mult Scler. 24(7):897-899. PMID: 29754529; PMCID: PMC5995597

Jawaid S, Kidd GJ, Wang J, Swetlik C, Dutta R, Trapp BD. (2018) Alterations in CA1 hippocampal synapses in a mouse model of fragile X syndrome. Glia 66(4):789-800. PMID: 29274095; PMCID: PMC5812820

Chomyk AM, Volsko C, Tripathi A, Deckard SA, Trapp BD, Fox RJ, Dutta R. (2017) DNA methylation in demyelinated multiple sclerosis hippocampus. Sci Rep. 7(1):8696. PMID: 28821749; PMCID: PMC5562763

Bai CB, Sun S, Roholt A, Benson E, Edberg D, Medicetty S, Dutta R, Kidd G, Macklin WB, Trapp B. (2016) A mouse model for testing remyelinating therapies. Exp Neurol. 283(Pt A):330-40. PMID: 27384502; PMCID: PMC5207347

Morris JK, Chomyk A, Song P, Parker N, Deckard S, Trapp BD, Pimplikar SW, Dutta R. (2015) Decrease in levels of the evolutionarily conserved microRNA miR-124 affects oligodendrocyte numbers in Zebrafish, Danio rerio. Invert Neurosci. 15(3):4. PMID: 26159098

Kremer D, Küry P, Dutta R. (2015) Promoting remyelination in multiple sclerosis: current drugs and future prospects. Mult Scler. 21(5):541-549. PMID: 25623245

Chen Z, Jalabi W, Hu W, Park HJ, Gale JT, Kidd GJ, Gossman ZC, Farabaugh KT, Erokwu C, Chen JT, Dutta R, Trapp BD. (2014) Microglial displacement of inhibitory synapses provides neuroprotection in the adult brain. Nat Commun. 5:4486-89. PMID:25047355; PMCID: PMC4109015

Huynh JL, Garg P, Thin TH, Yoo S, Dutta R, Trapp BD, Harotounian H, Zhu J, Donovan MJ, Sharp AJ, Casaccia P. (2014) Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains. Nat Neurosci. 17(1):121-30. PMID:24270187; PMCID: PMC3934491

Dutta R, Trapp BD. (2014) Relapsing and progressive forms of multiple sclerosis: insights from pathology. Curr Opin Neurol. 27(3):271-8. PMID:24722325; PMCID: PMC4132635

Dutta R, Chomyk AM, Chang A, Ribaudo MV, Deckard SA, Doud MK, Edberg DD, Bai B, Li M, Baranzini SE, Fox RJ, Staugaitis SM, Macklin WB, Trapp BD. (2013) Hippocampal demyelination and memory dysfunction are associated with increased levels of the neuronal microRNA miR-124 and reduced AMPA receptors. Ann Neurol. 73(5):637-45. PMID: 23595422; PMCID: PMC3679350

Nikolakopoulou AM, Dutta R, Chen Z, Miller RH, Trapp BD. (2013) Activated microglia enhance neurogenesis via trypsinogen secretion. Proc Natl Acad Sci USA. 110(21):8714-8719. PMID: 23650361; PMCID: PMC3666689

Dutta R. (2013) Gene expression changes underlying cortical pathology: clues to understanding neurological disability in multiple sclerosis. Mult Scler. 19(10):1249-1254. PMID: 23996595; PMCID: PMC3777669

Chang A, Staugaitis SM, Dutta R, Batt CE, Easley K, Chomyk A, Yong VW, Fox RJ, Kidd GJ, Trapp BD. (2012) Cortical remyelination: a new target for repair therapies in multiple sclerosis. Ann Neurol. 72(6):918-26. PMID: 23076662; PMCID: PMC3535551

Schmidt F, Eijnden M, Gobert RP, Saborio G, Carboni S, Alliod C, Pouly S, Staugaitis SM, Dutta R, Trapp B, Hooft van Huijsduijnen R. (2012) Identification of VHY/Dusp15 as a regulator of oligodendrocyte differentiation through a systematic genomics approach. PLoS One 7(7):e40457. PMID: 22792334; PMCID: PMC3394735

Dutta R, Chang A, Doud MK, Kidd GJ, Ribaudo MV, Young E, Fox RJ, Staugaitis SM, Trapp BD. (2011) Demyelination causes synaptic alterations in hippocampi from multiple sclerosis patients. Ann Neurol. 69(3):445-454. PMID: 21446020; PMCID: PMC3073544

Ishii A, Dutta R, Wark GM, Hwang SI, Han DK, Trapp BD, Pfeiffer SE, Bansal R. (2009) Human myelin proteome and comparative analysis with mouse myelin. Proc Natl Acad Sci USA. 106(34):14605-14610. PMID: 19706548; PMCID: PMC2732873

Dutta R, McDonough J, Chang A, Swami L, Siu A, Kidd GJ, Rudick RA, Mirnics K, Trapp BD. (2007) Activation of the ciliary neurotrophic factor (CNTF) signalling pathway in cortical neurons of multiple sclerosis patients. Brain 130(10):2566-2576. PMID: 17898009

Dutta R, McDonough J, Yin X, Peterson JW, Chang A, Torres T, Gudz T, Macklin WB, Lewis DA, Fox RJ, Rudick R, Mirnics K, Trapp BD. (2006) Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann Neurol. 59(3):478-489. PMID: 16392116

Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Kidd GJ, Dombrowski S, Dutta R, Lee JC, Cook DN, Jung S, Lira SA, Littman DR, Ransohoff RM. (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci. 9(7):917-924. PMID: 16732273

03/03/2022 |  

Cleveland Clinic Researchers Receive Two Grants to Study Pathogenesis of Multiple Sclerosis

Dr. Dutta is collaborating with other Cleveland Clinic researchers to explore possible novel causes of disease progression in multiple sclerosis, as well as potential therapeutic targets.