BrainMap

Mr. Marius Mihasan

PhD Habil

Professor - UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Other affiliations

Research Associate Professor - Department of Chemistry & Biomolecular Science, Clarkson University (United States of America)

Researcher | Teaching staff | Scientific reviewer | PhD supervisor

Dr. Marius MIHĂȘAN is a Professor of Biochemistry at Alexandru Ioan Cuza University of Iasi, Faculty of Biology, Romania. He holds a M.Sc. degree in Molecular Genetics from Alexandru Ioan Cuza University of Iasi, Romania in 2006. Dr. Mihasan worked for his PhD on the role of several genes from the catabolic megaplasmid pAO1 of Arthrobacter nicotinovorans in the lab of Prof. Dr. Roderich Brandsch, Albert-Ludwigs-University, Freiburg and prof. Dr. Vlad Artenie, Alexandru Ioan Cuza University of Iasi. He successfully defended his Ph.D. in 2009, did two consecutive PostDocs in Romania and then in 2017 received a Fulbright Fellow at Clarkson University, Potsdam, NY, USA. Dr. Mihasan was promoted to Full Professor at the Department of Biology at Alexandru Ioan Cuza University of Iasi, Romania in 2019. He is the coordinator of the BioActive research group and has published 61 peer-review research articles listed by WOS (H-index 21, November 2021) and 3 book chapters (Elsevier, Springer).

Web of Science ResearcherID: B-1119-2010

Curriculum Vitae (17/04/2024)

Expertise & keywords

Antiaggregation potential of 6-hydroxy-L-nicotine from Paenarthrobacter nicotinovorans pAO1 against amyloid peptide: in vitro and in vivo studies Call name: P 4 - Proiecte de cercetare exploratorie - PCE-2021
PN-III-P4-PCE-2021-1692 2022 - 2024

Role in this project: Key expert

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://cercetare.bio.uaic.ro/grupuri/bioactive/content/grants/PCE2022_hl.html

Abstract:

Alzheimer's disease (AD) is characterized by progressive degradation of memory processes, being associated with three major changes that occur in the brain: i) the formation of intra- and extracellular beta-amyloid deposits; ii) the appearance of neurofibrillary tangles and iii) the death of cholinergic neurons and a significant decrease in acetylcholine level. The identification of neuroprotective therapies for AD was dominated by the hypothesis of amyloid cascade and tau proteins. Unfortunately, both approaches have so far failed to provide an effective therapeutic strategy. The involvement of α7 and α4β2 subtypes of nicotinic receptors (nAChRs) in the pathogenesis of AD has led to the proposal of a new therapeutic approach. Immunohistochemical studies in the brains of patients with sporadic AD have shown that Aβ1-42 and α7nAChR are present in neuritic plaques and this interaction may be inhibited by α7nAChRs ligands. Nicotine, through its ability to bind to nAChRs is the ideal molecule for the development of new derivatives with therapeutic applications. The project aims to test the antiaggregating potential against Aβ1-42 of 6-hydroxy-L-nicotine (6HLN), derived from the metabolism of nicotine in the microorganism Paenarthrobacter nicotinovorans pAO1. To achieve this goal, the project activities will focus on evaluating the action of 6HLN in vitro on cell lines and in vivo on 5xFAD transgenic mice, in order to identify its therapeutic potential.

Sequencing the genome of a useful bacteria: Paenarthrobacter nicotinovorans – next step in extending it’s biotechnological applications Call name: P 4 - Proiecte de Cercetare Exploratorie, 2020
PN-III-P4-ID-PCE-2020-0656 2021 - 2023

Role in this project: Project coordinator

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://cercetare.bio.uaic.ro/grupuri/bioactive/content/grants/PCE2021.html

Abstract:

Paenarthrobacter nicotinovorans pAO1 is a nicotine degrading microorganism that shows promising applications in converting nicotine-containing waste into useful green chemicals. Its biotechnological applications are nevertheless hampered by the lack of knowledge and tools to perform genetic and metabolic engineering. After solving the nicotine-induced proteome of this bacteria, the project leader of the current proposal concluded that none of the draft genomes available for this strain are complete. The current application aims to provide the first complete and annotated genome of P. nicotinovorans pAO1, and, as such, the first complete genome of a nicotine degrading microorganism. In order to achieve this, P. nicotinovorans pAO1 gDNA will be isolated and whole-genome sequencing (WGS) will be performed using two platforms: NGS Illumina for reading depth and ONT MinION for scaffolding and assembling the genome. The quality of the assembly and annotation will be addressed using dRNA-seq and the already available raw proteomics data. The project will not only strengthen the much need bioinformatics know-how in the already existing team of the project leader, but also will group allow the group to generate a genome-scale metabolic model of the nicotine metabolism, and, consecutively, to develop high yield biotechnologies for production on nicotine derivatives.

Mobilitate cercetător cu experiență din diaspora Nicolae-Viorel Buchete Call name: PNCDI IV, P 5.2 - SP 5.2.2 - Proiecte de mobilitate pentru cercetători cu experiență din diaspora, MCD-2023
PN-IV-P2-2.2-MCD-2023-0165 2023 - 2023

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation:

Project website:

Abstract:

Mobilitate cercetător cu experiență din diaspora Cristian Ilioaia Call name: PNCDI IV, P 5.2 - SP 5.2.2 - Proiecte de mobilitate pentru cercetători cu experiență din diaspora, MCD-2023
PN-IV-P2-2.2-MCD-2023-0135 2023 - 2023

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation:

Project website:

Abstract:

Tricyclic 1,3-dithiolium flavonoids - New weapons to combat antibiotic resistance Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2019-2235 2020 - 2022

Role in this project: Key expert

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://cercetare.bio.uaic.ro/grupuri/bioactive/content/grants/ped2020.html

Abstract:

Increasing resistance of microbial pathogens against many available antibiotics is a medical problem of major concern all over the world. Antimicrobial resistance (AMR) poses a serious global threat due to the emergence, spread and persistence of multidrug resistant (MDR) bacteria or 'superbugs' such as the notorious Staphylococcus aureus. The discovery of new and more efficient antimicrobial drugs is therefore a matter of high priority among scientists and clinicians worldwide. A potential solution could be represented by tricyclic 1,3-dithiolium flavonoids with a bromine substituent at the benzopyran core (TSBrFls), a group of compounds with completely new structures, unrelated to any known natural compound, synthetized by our research group. The preliminary results showed that one particular TSBrFl - 4b displayed very potent antibacterial properties with low minimum inhibitory concentrations (0.24 μg/ml against S. aureus and 3.9 μg/ml against E. coli). The inhibitory effect was stronger compared to many antibiotics (gentamicin, ampicillin, kanamycin), natural or other synthetic flavonoids reported in literature. Moreover, a synergistic interaction with penicillin and fluconazole was recorded. The present proposal aims to validate TSBrFls as a new class of antimicrobial agents to be used against MDR strains. Further studies are necessary in order to: synthetize three new TSBrFls; optimize the synthesis procedure; test TSBrFls against a broader spectrum of MDR strains (including Candida sp.); evaluate the mode of action in relation with some important microbial resistance and virulence factors; assess shelf-life, solubility and cytotoxicity. The results obtained after the full implementation of the current proposal will allow us to move from the preliminary tests and experimental proof of concept (TRL3) to the validation of TSBrFls as new efficient antimicrobial agents (TRL4).

NEW SYNTHETIC FLAVONOIDS WITH ANTIMICROBIAL APPLICATIONS Call name: P 3 - SP 3.1 - Proiecte de mobilități, România-Franța (bilaterale)
PN-III-P3-3.1-PM-RO-FR-2019-0102 2019 - 2021

Role in this project: Key expert

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO); Université de Lille (FR)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.bio.uaic.ro/cercetare/grupuri/bioactive/content/grants/ro-fr2019.html

Abstract:

One of the most serious global threats of this century is the emergence and spread of antimicrobial-resistant pathogens. In agriculture, phytopathogenic microorganisms such as Fusarium, Botris or Zymoseptoria represent a major threat to both agricultural production and ecosystems stability. In the medical field, Candida species are responsible for over 64% of fungal infections, with a mortality rate of 40%. Therefore, finding new classes of more effective antimycotic drugs is a matter of maximum priority. In this context, this project proposes the development of a new class of antifungal products, represented by tricyclic flavonoids with different halogens as substituents at the benzopyran core. Preliminary results have shown that these flavonoids have important bacteriostatic and bactericidal properties. Additional studies, using the French partner's antifungal molecules experience, are needed to expand the antimicrobial spectrum of synthetic flavonoids. Also, collaboration will allow us to understand the mechanisms of action and to acquire knowledge on cytotoxicity. At the end of the project we will be able to propose a new high-efficiency antimycotic product, thus contributing to the strengthening of the scientific relationship between our laboratory and Lille University, France.

Steps towards an Arthrobacter nicotinovorans biotechnology for neuro-pharmaceuticals production Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente
PN-III-P1-1.1-TE-2016-0367 2019 - 2020

Role in this project: Project coordinator

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.bio.uaic.ro/cercetare/grupuri/bioactive/content/grants/te2019.html

Abstract:

6-hidroxy-nicotine (6HNic), a naturally occurring metabolite of Arthrobacter nicotinovorans was shown to bind the nicotinic acetylcholine receptors and to modulate their function. Experimental tests using laboratory rats have demonstrated the ability of 6HNic to cope with the acetylcholine depletion and to restore normal brain functions. 6HNic has been thereby identified as a high impact bio-pharmaceutical with application in the therapy of neurodegenerative disorders associated with low acetylcholine levels.

6HNic is produced in our group by using a genetically engineered strain of Arthrobacter nicotinovorans. The cultivation conditions currently employed allow for a yield of approx. 50 mg 6HNic / 100 ml culture. This is enough for common in-vitro and in-vivo lab test, but not near sufficient for the large scale test required for establishing the real therapeutic potential of 6HNic. The scope of the funding application is to develop a technology for high-yield production of the neuroprotective agent 6HNic using high-density cultures in a bio-fermenter. For this, a genetically engineered Arthrobacter strain will be created by knocking-out specific genes using suicidal vectors. The mutant strain will be further accommodated to a bio-reactor and the conditions for optimum 6HNic production will be evaluated. The final goal is to formulate an high-yield Arthrobacter based method for the production of 6HNic which would allow our group to further deepen the study of nicotine derivatives applications in biotechnology.

Steps towards an Arthrobacter nicotinovorans biotechnology for neuro-pharmaceuticals production Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2016-0177 2017 - 2018

Role in this project: Project coordinator

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.bio.uaic.ro/cercetare/grupuri/bioactive/content/grants/ped2017.html

Abstract:

6-hidroxy-nicotine (6HNic), a naturally occurring metabolite of Arthrobacter nicotinovorans was shown to bind the nicotinic acetylcholine receptors and to modulate their function. Experimental tests using laboratory rats have shown the ability of 6HNic to cope with the acetylcholine depletion and to restore normal brain functions. 6HNic has been thereby identified as a high impact bio-pharmaceutical with application in the therapy of neurodegenerative disorders associated with low acetylcholine levels. The scope of the funding application is to develop a technology for the production of the neuroprotective agent 6HNic in an industrial-like environment and to test it at a pilot scale. For this, a genetically engineered Arthrobacter strain will be created by knocking-out specific genes using suicidal vectors. The mutant strain will be further accommodated to a bio-reactor and the conditions for optimum 6HNic production will be evaluated. The final goal is to formulate a microbial based biotechnology for the production of 6HNic ready to be transferred to the industrial environment.

Nicotine - from toxic residue to metabolic derivatives with neuroprotective effects Call name:
PN-II 50BM/2016 2016 - 2017

Role in this project: Project coordinator

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.bio.uaic.ro/cercetare/grupuri/bioactive/content/grants/ro-ch2016.html

Abstract:

Both teams from Romania and P.R. China have the same main research interest: the nicotine catabolic pathway in bacteria. The research group from P.R. China coordinated by Tang H., PhD, have cloned, expressed, sequenced and characterized the enzymes nicotine oxidoreductase and 6-hydroxy-3-succinoylpyridine hydroxylase from Pseudomonas putida S16 and managed to show their implication in the transformation of nicotine to 2,5-dihydroxy-pyridine (DHP). The team from Romania, part of the a research group on ''Identification And Characterization Of Biological Active Molecules'' have identified the final degradation steps of nicotine metabolism in Arthrobacter nicotinovoras pAO1 and studied the effect the metabolic intermediate 6-hidroxy-nicotine on the learning and memory processes in rats. Both teams have knowledge, methods, plasmids and recombinant strains which allows the isolation of metabolic intermediates produced by the two bacteria: P. putida and A. nicotinovorans. As the objective of the project is to identify nicotine derivatives with neuroprotective effects, the combined scientific experience of the two teams will increase the repertoire of available nicotine derivatives for experimental testings. Beside the role in suppling the nicotine derivatives, each partner has at least one unique, complementary task. The group in Romania will be responsible for testing the selected nicotine derivatives on laboratory rats in order to identify their effects of memory and learning processes. The group from China is responsible of using genetic engineering techniques (gene-knockout, site-directed mutagenesis) for strain improvement in order to obtain the best yield for transformation of nicotine in valuable compounds. None of these complementary tasks can be fulfilled alone by the other partner.

Effects of 6-hydroxy-nicotine on chlorisondamine-induced oxidative stress and neurotoxicity: relevance for Alzheimer’s disease Call name: Projects for Young Research Teams - RUTE -2014 call
PN-II-RU-TE-2014-4-0106 2015 - 2017

Role in this project: Project coordinator

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.bio.uaic.ro/cercetare/grupuri/bioactive/content/grants/te2015.html

Abstract:

The search for neuroprotective therapeutics for Alzheimer’s disease (AD) has been recently geared toward the identification of modulators for nicotinic acetylcholine receptors (nAChR). Using computational methods, the Arthrobacter nicotinovorans metabolic intermediate 6-hidroxy-nicotine (6HNic) have been identified as a putative nAChR ligand. The cognitive-functions tests performed on normal rats showed that chemically synthesized 6HNic has positive effects on spatial memory, mainly by decreasing brain oxidative stress.The current research funding application aims to form a young team with the goal to isolate 6HNic and to evaluate its potential of improving the cognitive and non-cognitive functions in a rodent model of AD. For this, the Arthrobacter nicotinovorans enzyme responsible for 6HNic production will be cloned, expressed, purified and further used to produce the compound in an in-vitro reaction. After its isolation by HPLC from the reaction mixture, 6HNic will be injected in chlorisondamine-treated rats and its neuroprotective and anti-oxidant properties will be assessed using a combination of behavioral tests, flow-cytometry and biochemistry techniques. Also, the systemic toxicity as well as pro-apoptotic properties will be investigated, in an attempt to fully characterize the compound and to conclude its applicability in the field of AD.

Applications of some biomolecules with antifungal properties in plant protection Call name: Programul de actiuni Integrate Romania-Franta (bilaterale)
PN-II-CT-RO-FR-2014-2-0033 2014 -

Role in this project: Key expert

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO); Université Lille 1 (FR)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website:

Abstract:

Phytopathogenic microorganisms represent a major threat worldwide for both agricultural production and ecosystem stability. For this reason, farmers became dependent on the use of chemicals as a method of pest control. Excessive use of plant protection products has however negative consequences: soil and atmosphere pollution, water quality degradation, biodiversity loss in the agricultural ecosystems, threatening human health. In this context, the project proposes as an alternative to traditional chemical fungicides the use of lipopeptide (iturine, surfactin and fengicine) produced by species of the genus Bacillus for the biocontrol of the phytopathogenic fungus Fusarium oxysporum. Using purified biomolecules, characterized and tested by French researchers from the University of Science and Technology of Lille 1, we intend to test the biocontrol potential of the lipopeptides within the specific pathosystem of ornamental plants grown in the Botanical Garden of Iasi: Narcissus and Iris. The results of these investigations will be later extended to other plant species with economic value.

FILE DESCRIPTION	DOCUMENT
List of research grants as project coordinator or partner team leader
Significant R&D projects for enterprises, as project manager
R&D activities in enterprises
Peer-review activity for international programs/projects