Research activity: Neuro-immune interactions in pain pathogenesis

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Teaching activity: Animal Physiology, Physiopathology, Neurobiology of the homeostatic behaviors

 

Biographical Profile

Violeta Ristoiu got her PhD in Biology at the University of Bucharest, Faculty of Biology in 2000. She undertook several trainings at Hamburg University-Germany, University of Copenhagen- Denmark, Okazaki Institute for Integrative Bioscience-Japan and Alnylam Pharmaceuticals- Cambridge, MA, USA. In 2015 she was a Fulbright Visiting Scholar at the University of Nebraska Medical Center, Department of Pharmacology and Experimental Neurosciences.

Research activity

Neuropathic pain is a complex syndrome caused by a primary lesion or s dysfunction in the central nervous system (CNS) or peripheral nervous system (PNS). Its pathogenesis is not only confined to changes in the activity of neuronal systems, but also involves interactions between neurons, immune cells and immune-like glial cells mediated by inflammatory cytokines and chemokines. Among the cells involved in the neuro-immune interactions, microglia and macrophages have a very important pro-nociceptive role.

In our group we have the following running projects:

1) Study the role of Iba-1 protein in the modulation of the microglia and macrophages contribution to neuropathic pain pathogenesis. In the central nervous systems, microglia are not dormant, but perform immune surveillance, extending and retracting their ramified processes without overall cell displacement. After an injury to the peripheral nervous system microglia rapidly activate: their cell body increases in size, proximal processes become thicker, distal branches are less ramified, specific membrane ruffles develop, and the cells move to the damaged site where they show increased phagocytic activity and release of pro-inflammatory mediators. All these phenotypic changes are caused by rapid changes of the microglia cytoskeleton. Iba-1 is a cytoskeleton protein, a specific marker for microglia and macrophages and an essential protein for their survival and pro-inflammatory activity.

2) Biocompatible system for sustaining peripheral nerve regeneration

3) Investigation of the modulatory effects of CXCL1 and CXCL2 chemokines on primary sensory neurons from dorsal root ganglia and the role of TRPV1 receptors in mediating these effects.

4) K+ channels as markers of activation and therapeutic targets in microglia.

Members of the group

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Financing

The research activity is financed by grants from UEFISCDI, Sciex-NMS, IASP (International Association for the Study of Pain) and ICGEB (International Centre for Genetic Engineering and Biotechnology).

• 2020-2022, "Validation of Iba1 as a new therapeutic target in human microglia" 374/PED (PN-III-P2-2.1-PED-2019-3103)
• 2018-2020, “Biocompatible system for sustaining peripheral nerve regeneration”, co-PI in collaboration with Dr. Monica Neagu from the National Institute “Victor Babes” – a subproject of the complex project “Innovative advanced approaches for predictive regenerative medicine”, Director: Prof. Dr. Marieta Costache, Financing: UEFISCDI
• 2017-2019, “Iba-1 macrophages contribution to peripheral neuropathic pain development”, PI: Assoc. Prof. Violeta Ristoiu, Financing: ICGEB (International Centre for Genetic Engineering and Biotechnology).
• 2015-2017 “Investigating the K channels in the microglia and their role in pain pathogenesis”, co-PI in collaboration with Dr. Marc Suter from the University of Lausanne, Switzerland. Financing: IASP (International Association for the Study of Pain)
• 2014-2016 "Validation of the combined use of RNAi technology and mass spectrometry for the identification of therapeutic targets in microglia, important for neuropathic pain and Alzheimer disease", PCCA 205/2014, Partnerships, PI: Assoc. Prof. Violeta Ristoiu, Financing: UEFISCDI
• 2013-2014 “Contribution of Iba-1 protein to the neuropathic pain mechanism", Home mentor in collaboration with Prof. Isabelle Decostred from the University of Lausanne, Switzerland. Financing: Scientific Exchange Program (Sciex-NMS)
• 2012-2014 Bilateral project Romania-Greece “The role of small GTPases and of ASIC channels in the normal and pathological cortex”, co-PI in collaboration with Dr. Domna Karagogeos from the Institute de Molecular Biology and Biotechnology, Crete University. Financing: UEFISCDI
• 2011-2014 "Cellular and molecular mechanisms of diabetic neuropathy: contributions of the immune system and of the glycation agents", Ideas, 117/2011, PI: Assoc. Prof. Violeta Ristoiu, Financing: UEFISCDI
• 2007-2009 CNCSIS, “Effects of polyunsaturated fatty acids on TRPV1 channels expressed in dorsal root ganglia neurons. Implication for pain pathogenesis”, PI: Assoc. Prof. Violeta Ristoiu, Financing: UEFISCDI

Colaboratori

• Dr. Ștefana Petrescu, Institutul de Biochimie al Academiei Romane
• Dr. Luigi Silvestro, Pharmaserv SRL
• Dr. Adriana Georgescu, Institutul de Biologie si Patologie Celulara “Nicolae Simionescu”
• Prof. Koji Shibasaki, Gunma University, Japan
• Prof. Damir Sapunar, University of Split School of Medicine, Croatia
• Dr. Marc Suter, University of Lausanne, Switzerland
• Prof. Isabelle Decostred, University of Lausanne, Switzerland
• Prof. Huangui Xiong, University of Nebraska Medical Center, USA

Selected publications

• Deftu A, Filippi A, Gheorghe RO, Ristoiu V, CXCL1 activates TRPV1 via Gi/o protein and actin filaments, Life Sciences, https://doi.org/10.1016/j.lfs.2017.09.041, 2017
• Deftu A, Filippi A, Shibasaki K, Gheorghe RO, Chiritoiu M, Ristoiu V, CXCL1 and CXCL2 chemokines modulate the activity of TRPV1+/IB4+ cultured rat dorsal root ganglia neurons upon short-term and acute application, Journal of Physiology and Pharmacology, 68 (3): 385-395, 2017
• Filippi A, Caruntu C, Gheorghe RO, Deftu A, Amuzescu B, Ristoiu V, Catecholamines reduce TRPV1 desensitization in cultured dorsal root ganglia neurons, Journal of Physiology and Pharmacology, 67 (6): 843-850, 2016
• Alexandru N, Andrei E, Niculescu L, Dragan E, Ristoiu V, Georgescu A, Microparticles of healthy origins improve endothelial progenitor cell dysfunction via microRNA transfer in an atherosclerotic hamster model, Acta Physiologica, doi: 10.1111/apha.12896, 2017
• Ristoiu V, Contribution of macrophages to peripheral neuropathic pain pathogenesis, mini-review, Life Sciences, 26;93(23):870-81, 2013
• Ton TBH, Chen Q, Gaina G, Tucureanu C, Georgescu A, Strungaru C, Flonta ML, Sah DW, Ristoiu V, Activation profile of dorsal root ganglia Iba-1 (+) macrophages varies with the type of lesion in rats, Acta Histochemica, 115(8):840-50, 2013
• Ristoiu V, Shibasaki K, Uchida K, Zhou Y, Ton TBH, Flonta ML, Tominaga M, Hypoxia-induced sensitization of transient receptor potential vanilloid 1 involves activation of hypoxia-inducible factor-1 and PKC, Pain, 152(4), 936-945, 2011
• Ton TBH, Marin A, Dinu C, Banciu D, Flonta ML, Ristoiu V, Hypoxia and high glucose activate TTX-R Na+ channels through PKA and PKC, Acta Neurobiologiae Experimentalis, 70, 1-11, 2010