Maria Rosalia Pasca
Maria Rosalia Pasca
e-mail:
affiliation: Università di Pavia
research area(s): Genetics And Genomics
Course: Genetics, Molecular and Cellular Biology
University/Istitution: Università di Pavia
Maria Rosalia Pasca
DATE OF BIRTH: 11/07/1971
EDUCATION
· 21/03/1997: Degree in Natural Sciences (Mark: 110/110), University of Bari, Italy.
· 04/02/2002: PhD in Genetics and Molecular Evolution (XIII cycle), University of Bari, Italy.
ACADEMIC POSITION
· October 2006-February 2015: Researcher in Microbiology (BIO/19), Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, Italy.
· 1st March 2015-Present: Associate Professor in Microbiology (BIO/19), Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, Italy.
· 6th April 2017: National scientific qualification to Full Professor in Microbiology (05/I2).
DIDACTICS
· She is involved in the following teachings in the Laurea Magistralis in Experimental and Applied Biology (University of Pavia): “Environmental Microbiology” (3 CFU; from A.A. 2010-2011), “Microbiological analysis” (5 CFU; from A.A. 2008-2009).
· From A.A. 2014-2015, she teaches “General microbiology” (6 CFU) in the Laurea Magistralis in Engineering for the environment and the territory, Università di Pavia.
· From A.A. 2013-2014, she teaches in the following Speciality schools (Teaching Abilitation Courses): “PAS (Percorsi Abilitanti Speciali)” and “TFA (Tirocinio Formativo Attivo)” for the classes A059 and A060.
· From A.A. 2014-2015, she is Coordinator for A50 class (Natural, chemical and biological sciences) of PAS/TFA/FIT Speciality schools, necessary to obtain the qualification to became School teacher.
· From A.A. 2007-2008, she is Member of the College of the Professors of the Doctorate in Genetics, Molecular and Cellular Biology, University of Pavia, Italy.
EXPERTISE
Tuberculosis, Mycobacterium tuberculosis, Bacterial pathogens, Nontuberculous Mycobacteria, Mycobacterium abscessus, Drug discovery, Mechanisms of drug resistance/action, Drug target, gut microbiota, colorectal cancer.
GRANTS
· Principal Investigator in a big Project on Tuberculosis Drug Discovery topic funded by European Commission (IMI 2) (about € 600.000, 1/2020-12/2025).
· Principal Investigator in the Project: “New weapons against Mycobacterium abscessus and other nontuberculous Mycobacteria” funded by Italian Cystic Fibrosis Research Foundation” (FFC; € 58.000, 09/2018-08/2020).
· She has been participant in three projects funded by European Commission (V, VI, and VII Framework programs) on the Tuberculosis topic. The last project was “More medicines for tuberculosis (MM4TB).
MAIN ACHIEVEMENTS AND AWARDS FOR HER SCIENTIFIC ACTIVITY
· The following international patent was sold to Sentinel Diagnostics (http://www.sentinel.it/it/), This company is developing two diagnostic kits for the identification of mycobacterial clinical isolates resistant to benzothiazinones.
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Riccardi G, Manina G, Pasca MR. 2008. “An effective new drug target for the treatment of tuberculosis” (PCT/EP2008/001088).
· The following article has been cited as one of the key articles concerning tuberculosis, published in 2009 (Nature Medicine 15: 1349):
Makarov V et al. 2009. Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis. Science 324:801-804.
· The following Abstract was selected for a personal oral presentation at the international congress “Embo tuberculosis 2016 (Paris, 19-23/09/2016):
· Chiarelli LR, Esposito M, Orena BS, Mori G, Buttari N, Degiacomi G, Gosetti F, Manfredi M, Ekins S, Mikušová K, Bellinzoni M, Manganelli R, Marengo E, Ballell-Pages L, Riccardi G, Pasca MR. “Mycobacterium tuberculosis CTP synthetase and pantothenate kinase: two promising targets for the development of multitargeting drugs”.
INVITATION AS SPEAKER
· Invitation for the following lecture (I.N.M.I. "L. Spallanzani" I.R.C.C.S., Roma, 28/05/2009): “New drugs and a novel cellular target against tuberculosis”.
· Invitation as speaker to a National Meeting (Firenze, 10-11/11/2016): “Microbioma intestinale e carcinogenesi”. Convegno Nazionale GISCOR (Workshop: “Genetica e neoplasie del colon-retto: il ruolo delle analisi molecolari all’interno del programma di screening”).
PERSONAL BIBLIOGRAPHY
She is author of 56 peer-reviewed papers (8 as 1st author, 9 as last author, 10 as corresponding author), 4 chapters for books, 2 international patent applications and several international and national communications to congresses.
Bibliometric Indicators (at 17th October 2019):
TOTAL IF = 275.549;
TOTAL H INDEX = SCOPUS: 26; WOS: 26; GOOGLE SCHOLAR: 29;
TOTAL CITATIONS: SCOPUS: 2364; WOS: 2248; GOOGLE SCHOLAR: 3083.
MAIN FIELDS OF RESEARCH
Searching for new antitubercular drugs and novel targets
Tuberculosis remains the leading cause of mortality due to a bacterial pathogen, Mycobacterium tuberculosis. Moreover, M. tuberculosis drug-resistant strains are becoming a threat to public health worldwide. Consequently, there is an urgent necessity of new anti-TB drugs. We have identified the target of the benzothiazinones (BTZ), that is DprE1, an enzyme involved in the biosynthesis of arabinogalactan, a cell wall component. One BTZ derivative is in clinical human trials in Russia and in Europe. The study of the mechanism of action and resistance of other new antitubercular drugs is in progress.
In 2020 a new Project funded by European Commission on this topic will start. The aims of our group will be the followings: study of the mechanism of action/resistance of new compounds; study of drug combinations; activity of the new compounds against drug-resistant M. tuberculosis clinical isolates.
Collaborations: Makarov V (Bakh Institute of Biochemistry, Russian Academy of Science, Moscow, Russia); Mikusova K (Comenius University, Bratislava, Slovakia); Baltas M (CNRS, Toulouse, France); Ainsa JA (University of Zaragoza, Zaragoza, Spain); Cole ST (Institut Pasteur, Paris, France).
New weapons against Mycobacterium abscessus and other nontuberculous Mycobacteria (Funded by FFC 2018)
Nontuberculous mycobacteria (NTM) are emerging as important pathogens in cystic fybrosis (CF) lung disease worldwide with an estimated prevalence of about 9-24%. Mycobacterium avium complex and Mycobacterium abscessus complex include the NTM species most commonly identified in CF; the Mycobacterium abscessus strains are the most spread in Europe. The M. abscessus treatments are further complicated by the diffusion of multidrug-resistant strains. In these cases, the surgical resection of infected lung tissue could be beneficial in selected patients. Moreover, unsuccessful M. abscessus eradication is considered a contraindication for lung transplantation, being associated with treatment failure and increased mortality.
Consequently, new more active drugs are urgently needed against M. abscessus.
In this project, taking advantage of our experience in tuberculosis research, we moved all our knowledge in the new challenging NTM field.
We have already screened in vitro against M. abscessus growth more than 500 compounds, finding only one active, also against drug-resistant clinical strains. The characterization of its mechanism of action/resistance is in progress.
Dr. Makarov is synthesizing new compounds ad hoc against M. abscessus and we will continue to test them with the hope to find novel active ones. Moreover, we are using novel approaches with the hope to finding active compounds against this emerging pathogen.
Collaboration: Makarov V (Bakh Institute of Biochemistry, Russian Academy of Science, Moscow, Russia); Prof. Fabrizio Manetti (Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy).
1. Neres J, Hartkoorn R, Chiarelli L, Gadupudi R, Pasca MR, Mori G, Farina D, Savina S, Makarov V, , et al. 2-Carboxyquinoxalines kill Mycobacterium tuberculosis through non-covalent inhibition of DprE1. ACS Chem Biol. 2015.10:705-14.
2. Perdigão G, Deraeve C, Mori G, Pasca MR, Pratviel G, Bernardes-Génisson V. 2015. Pyridine-3,4-dicarboximide as starting material for the total synthesis of the natural product eupolauramine and its isomer iso-eupolauramine endowed with anti-tubercular activities. Tetrahedron. 2015. 71:1555-1559.
3. Mori G, Chiarelli LR, Esposito M, Makarov V, Bellinzoni M, Hartkoorn RC, Degiacomi G, Boldrin F, Ekins S, de Jesus Lopes Ribeiro AL, Marino LB, Centárová I, Svetlíková Z, Blaško J, Kazakova E, Lepioshkin A, Barilone N, Zanoni G, Porta A, Fondi M, Fani R, Baulard AR, Mikušová K, Alzari PM, Manganelli R, de Carvalho LP, Riccardi G, Cole ST, Pasca MR. Thiophenecarboxamide derivatives activated by EthA kill Mycobacterium tuberculosis by inhibiting the CTP synthetase PyrG. Chem Biol. 2015. 23;22:917-27.
4. Chollet A, Mori G, Menendez C, Rodriguez F, Fabing I, Pasca MR, Madacki J, et al. Design, synthesis and evaluation of new GEQ derivatives as inhibitors of InhA enzyme and Mycobacterium tuberculosis growth. Eur J Med Chem. 2015. 101:218-35.
5. Albesa-Jové D, Comino N, Tersa M, Mohorko E, Urresti S, Dainese E, Chiarelli LR, Pasca MR, Manganelli R, Makarov V, et al. The Redox State Regulates the Conformation of Rv2466c to Activate the Antitubercular Prodrug TP053. J Biol Chem. 2015. 290:31077-89.
6. Veau D, Krykun S, Mori G, Orena BS, Pasca MR, et al. Triazolophthalazines: Easily Accessible Compounds with Potent Antitubercular Activity. ChemMedChem. 2016. 11:1078-89.
7. Meneghetti F, Villa S, Gelain A, Barlocco D, Chiarelli LR, Pasca MR, Costantino L. Iron acquisition pathways as targets for antitubercular drugs. Curr Med Chem. 2016. 23:4009-4026.
8. Chollet A, Stigliani JL, Pasca MR, Mori G, Lherbet C, Constant P, et al. Evaluation of the inhibitory activity of (aza)isoindolinone-type compounds: toward in vitro InhA action, Mycobacterium tuberculosis growth and mycolic acid biosynthesis. Chem Biol Drug Des. 2016. 88:740-755.
9. Matviiuk T, Madacki J, Mori G, Orena BS, Menendez C, Kysil A, André-Barrès C, Rodriguez F, Korduláková J, Mallet-Ladeira S, Voitenko Z, Pasca MR, et al. Pyrrolidinone and pyrrolidine derivatives: Evaluation as inhibitors of InhA and Mycobacterium tuberculosis. Eur J Med Chem. 2016. 123:462-475.
10. Chiarelli LR, Mori G, Esposito M, Orena BS, Pasca MR. New and old hot drug targets in tuberculosis. Curr Med Chem. 2016. 23:3813-3846.
11. Mori G, Chiarelli LR, Riccardi G, Pasca MR. New prodrugs against tuberculosis. Drug Discov Today. 2017. 22:519-525.
12. Esposito M, Szadocka S, Degiacomi G, Orena BS, Mori G, Piano V, Boldrin F, Zemanová J, Huszár S, Barros D, Ekins S, Lelièvre J, Manganelli R, Mattevi A, Pasca MR, et al. A Phenotypic Based Target Screening Approach Delivers New Antitubercular CTP Synthetase Inhibitors. ACS Infect Dis. 2017. 3:428-437.
13. Oliveira PFM, Guidetti B, Chamayou A, André-Barrès C, Madacki J, Korduláková J, Mori G, Orena BS, Chiarelli LR, Pasca MR, et al. Mechanochemical Synthesis and Biological Evaluation of Novel Isoniazid Derivatives with Potent Antitubercular Activity. Molecules. 2017. 22(9). pii: E1457.
14. Chiarelli LR, Mori G, Orena BS, Esposito M, Lane T, de Jesus Lopes Ribeiro AL, Degiacomi G, Zemanová J, Szádocka S, Huszár S, Palčeková Z, Manfredi M, Gosetti F, Lelièvre J, Ballell L, Kazakova E, Makarov V, Marengo E, Mikusova K, Cole ST, Riccardi G, Ekins S, Pasca MR. A multitarget approach to drug discovery inhibiting Mycobacterium tuberculosis PyrG and PanK. Sci Rep. 2018. 8(1):3187.
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15. Mori G, Rampelli S, Orena BS, Rengucci C, De Maio G, Barbieri G, Passardi A, Casadei Gardini A, Frassineti GL, Gaiarsa S, Albertini AM, Ranzani GN, Calistri D, Pasca MR. Shifts of Faecal Microbiota During Sporadic Colorectal Carcinogenesis. Sci Rep. 2018. 8(1):10329.
16. Mori G, Orena BS, Franch C, Mitchenall LA, Godbole AA, Rodrigues L, Aguilar-Pérez C, Zemanová J, Huszár S, Forbak M, Lane TR, Sabbah M, Deboosere N, Frita R, Vandeputte A, Hoffmann E, Russo R, Connell N, Veilleux C, Jha RK, Kumar P, Freundlich JS, Brodin P, Aínsa JA, Nagaraja V, Maxwell A, Mikušová K, Pasca MR, et al. The EU approved antimalarial pyronaridine shows antitubercular activity and synergy with rifampicin, targeting RNA polymerase. Tuberculosis (Edinb). 2018. 112:98-109.
17. Meta E, Brullo C, Tonelli M, Franzblau SG, Wang Y, Ma R, Baojie W, Orena BS, Pasca MR, et al. Pyrazole and imidazo[1,2-b]pyrazole derivatives as new potential anti-tuberculosis agents. Med Chem. 2019. 15:17-27.
18. Mori G, Orena BS, Cultrera I, Barbieri G, Albertini AM, Ranzani GN, Carnevali I, Tibiletti MG, Pasca MR. Gut Microbiota Analysis in Postoperative Lynch Syndrome Patients. Front Microbiol. 2019;10:1746.
Project Title:
Study of the mechanism of action and of resistance of new antitubercular drugs
In 2020 a new big Project funded by European Commission on this topic will start. The aims of our group will be the followings: study of the mechanism of action/resistance of new compounds; study of drug combinations; activity of the new compounds against drug-resistant M. tuberculosis clinical isolates. Moreover in this project for the most promising antitubercular compounds preclinical and clinical trials will be performed.
Collaborations: Ainsa JA (Mycobacterial Genetics Group at the Department of Microbiology, Preventive Medicine and Public Health, Faculty of Medicine, University of Zaragoza, Zaragoza, Spain); Cole ST (Institut Pasteur, Paris, France).


Project Title:
New drugs against Mycobacterium abscessus
In this project, taking advantage of our experience in tuberculosis research, we are characterizing the mechanism of action/resistance of compounds active against Mycobacterium abscessus, an emerging pathogen among cystic fibrosis patients.
Dr. Makarov is synthesizing new compounds ad hoc against M. abscessus and we will continue to test them with the hope to find novel active ones. Moreover, we are using novel approaches with the hope to finding active compounds against this worrisome pathogen.
Collaboration: Makarov V (Bakh Institute of Biochemistry, Russian Academy of Science, Moscow, Russia); Prof. Fabrizio Manetti (Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy).