Ranjan Dutta, PhD
Assistant Staff
Assistant Professor, Molecular Medicine, CCLCM-CWRU
Email: [email protected]
Location: Cleveland Clinic Main Campus
Research
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.
Biography
Ranjan Dutta, PhD is a principal investigator in the Department of Neurosciences at the Cleveland Clinic Lerner Research Institute (LRI). He also holds faculty appointments at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Kent State University and Cleveland State University.
After completing his PhD in human genetics in Kolkata, India, Dr. Dutta joined the Cleveland Clinic for a postdoctoral fellowship in the laboratory of Dr. Bruce Trapp investigating the cellular responses to demyelination in multiple sclerosis (MS) and related disease states. During his postdoctoral work, he standardized protocols and assays to examine gene and genetic modifiers in human postmortem tissues. He rose through the ranks from Postdoctoral Fellow to Associate Staff and running his independent research program after obtaining multiple funding awards from the National Multiple Sclerosis Society (USA) and NINDS/NIH.
Dr. Dutta’s current research is focused on investigating the pathogenesis of neurological disability in MS. Two major factors underlie progressive disability in MS patients: 1) neuro-axonal loss following demyelination, and 2) remyelination failure. His research goals are therefore focused on a) neuronal changes following demyelination in MS patients, and b) enhancing remyelination following demyelination. To maximize translational efficacy, his lab takes a ‘reverse approach’ where histopathology/molecular changes in MS brains are replicated in vitro and in preclinical models for more detailed mechanistic study. Several fundamental observations regarding MS pathogenesis have emerged from his studies, including neuronal mitochondrial changes as a cause of axonal degeneration and hippocampal demyelination as a cause of cognitive dysfunction. His group has been at the forefront of identifying microRNAs and DNA methylation patterns that regulate gene expression in MS. His current investigations include neuronal pathology and differences in remyelination efficiency in progressive MS using a combination of histopathology, molecular and epigenetic markers in MS brains, in vitro approaches, and preclinical models. He is also interested in developing new approaches to determine cellular changes in MS brains. Dr. Dutta sits on the editorial board of Scientific Report, Multiple Sclerosis Journal, Multiple Sclerosis Therapeutics, and Multiple Sclerosis and Related Disorders. He also sits on several grant review panels constituted by the National Institute of Health, USA and Multiple Sclerosis Societies from the United States, United Kingdom, Australia, and Italy as well as the European Research Council.
Education & Professional Highlights
Appointed
2006
Medical Education - Jadavpur University
Calcutta,
2001
Graduate School - University of Calcutta
Calcutta,
1995
Undergraduate - University of Calcutta
Calcutta,
1993
Research
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.
Our Team
Selected Publications
View publications for Ranjan Dutta, PhD
(Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)
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
Careers
Research News
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.
New research led by Ranjan Dutta, PhD demonstrates the importance of controlled microRNA expression for effective remyelination.