Department of Neurosciences
Ranjan Dutta, Ph.D.
Assistant Professor, Molecular Medicine, CCLCM-CWRU
Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone: (216) 445-5964
Fax: (216) 444-7927
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.
In other words ...
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.
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