Characterization of BRCA1-induced genomic instability and identification of a novel PARP1 interactor

(1)

1

REPORT SULLE ATTIVITÀ SVOLTE

REPORT ON THE ACTIVITIES UNDERTAKEN

Corso di dottorato / PhD Program _Scienze Cliniche e Traslazionale_

Curriculum (se previsto / if applicable) _______________________________

Cognome / Family Name _Lodovichi _

Nome / Name _Samuele_

Data nascita / Date of Birth _19/08/1987_

Luogo nascita / Place of Birth _Cecina_

Data di rilascio del titolo / Date of issue of the certificate ________________________

Eventuale valutazione (se prevista) / Subsequent evaluation (if applicable) __________

Supervisore / Supervisor _Alvaro Galli_

Commissione di esame finale (Nome, cognome e ente di afferenza) / Final exam board (Name,

Family Name and relevant department) ______________________________________________

ATTIVITÀ FORMATIVE / FORMATIVE ACTIVITIES

I anno di corso / I course year (anno accademico / academic year 2014/15)

DENOMINAZIONE DEL CORSO / NAME OF THE COURSE DURATA / DURATION (in ore / in hours) SEDE / LOCATION (indicare Università o altra sede di svolgimento / indicate the university or other course location) DOCENTE / PROFESSOR (nome e cognome / name and family name) VOTAZIONE / FINAL MARK GIUDIZIO / EVALUATION LINGUA UTILIZZATA (italiano, inglese, altra lingua / Italian, English or other languages)

Corsi del dottorato frequentati/ Doctorate courses attended

Altri corsi/ Other courses Seminari di ricerca/Research seminars (argomento e ore di svolgimento / topic and number of hours carried out)

1.Re-purposing FDA-approved antibiotics to eradicate cancer stem cells (Dr. Micheale Lisanti) 2.Polyphenols increasing clues of interactions with mithochondria and vascular endothelial growth factor (Dr. Bargiacchi)

(2)

2

PERIODO DI SVOLGIMENTO (da ___ a ____ / a ___ to ___) ENTE OSPITANTE

(nome, luogo ed eventuale supervisore / name, location

and subsequent supervisor)

ATTIVITÀ SVOLTE E RISULTATI ACTIVITIES CARRIED OUT AND RESULTS

Esperienze di ricerca presso altre strutture / Research experience in other institutions Attività o borse all’estero/Training or Scholarship abroad

II anno di corso / II course year (anno accademico / academic year 2015/16)

Corsi del Dottorato frequentati/ Doctorate Courses Attended

Statistica 40 Porta Nuova Prof. Mario

Miccoli

Idoneo Italiano

Altri corsi/ Other Courses Seminari di ricerca/Research Seminars (argomento e ore di svolgimento / topic and number of hours carried out) All of it PERIODO DI SVOLGIMENTO (da ___ a ____ / a ___ to ___) ENTE OSPITANTE

ATTIVITÀ SVOLTE E RISULTATI

ACTIVITIES CARRIED OUT AND RESULTS

Esperienze di

ricerca presso altre strutture / Research experience in other institutions Attività o borse all’estero/Training or Scholarship abroad

(3)

3 III anno di corso / III course year (anno accademico / academic year 2016/17)

Corsi del Dottorato frequentati/ Doctorate Courses Attended

Altri corsi/ Other Courses Seminari di ricerca/Research Seminars (argomento e ore di svolgimento / topic and number of hours carried out)

1. May 31th 2016 Seminar: The dogmas of type 2 diabetes: time for reconsideration from a new angle? Speaker: Marc Prentki,

2.Le Omiche in Medicina Interna (Prof. Ele Ferrarini) June 21th 2016 3. PhD day (8 febbraio)

4. La prospettiva di genere nella ricerca biomedica: esperienze nell'Università di Pisa 5. PhD day (26 settembre) PERIODO DI SVOLGIMENTO (da ___ a ____ / a ___ to ___) ENTE OSPITANTE

ATTIVITÀ SVOLTE E RISULTATI

ACTIVITIES CARRIED OUT AND RESULTS

Esperienze di

ricerca presso altre strutture / Research experience in other institutions Attività o borse all’estero/Training or Scholarship abroad

Da 20/02/2017 a

12/08/2017

Moffitt Cancer Center,

Tampa, Florida.

Supervisor: Dr. Alvaro N.

Monteiro

Analysis of putative interaction between PARP1 and SART1 proteins in human cell lines.

TITOLO DELLA TESI / TITLE OF THE PHD THESIS

Characterization of BRCA1-induced genomic instability and identification of a novel PARP1

interactor

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4

PROGETTO DI RICERCA/RESEARCH PROJECT

Based on results that expression of BRCA1 cancer related missense variants increases spontaneous

homologous recombination in diploid strain of the yeast Saccharomyces cerevisiae, in this study we

used this model organism to study contribution of BRCA1 partners in genomic instability caused by

BRCA1 pathogenic variants expression. Then I analyzed effect of BRCA1 expression on gene

reversion in phase-arrested cells, in order to eventually relate these events increases to a particular

phase of the cell cycle, therefore giving indication about its pathogenicity to a phase-specific

mechanism. I also analyzed recombination induction of DNA damage agent MMS in cell expressing

pathogenic variants of BRCA1 and new candidates PARP1 interactors starting from a wide-genome

yeast screening data.

CONVEGNI, WORKSHOP E SEMINARI IN ITALIA E ALL’ESTERO/ CONFERENCES, WORKSHOPS,

SEMINARSATTENDED IN ITALY AND ABROAD

Lodovichi S, La Ferla M, Rocchi G, Mercantanti A, Cervelli T, Caligo MA e Galli A. “A genome-wide screening

in yeast identifies genes potentially involved in PARP1 regulation” at HEREDITARY BREAST & OVARIAN

CANCER congress (January 2015), Bari, Italy.

Lodovichi S, Vitello M, Cervelli T, Galli A. “Intracellular localization and cell cycle effect of cancer related

BRCA1 missense variants in yeast” 27th International Congress on Yeast Genetics and Molecular Biology,

6-12 September 2015, Levico Terme, Trento, Italy

Lorenzoni A, Lodovichi S, Cervelli T, Galli A. “Cell cycle dependency of BRCA1-induced gene reversion in

Saccharomyces cerevisaie” FISV (Federazione Italiana Scienze della Vita) 2016 XIV Congress, Rome, Italy,

20-23 September 2016

(No poster)

AACR Annual Meeting 2017, April 1 - 5 2017, Walter E. Washington Convention Center, Washington, D.C.,

USA

EVENTUALE ATTIVITÀ DI RICERCA IN AZIENDA / SUBSEQUENT RESEARCH ACTIVITIES IN

COMPANIES

PUBBLICAZIONI (N.B. depositate in ARPI) / PUBLICATIONS (Note: Publications must be stored in

ARPI

TIPOLOGIA

PUBBLICAZIONE

ALTRI

AUTORI

COAUTHORS

TITOLO DELLA

PUBBLICAZIONE

TITLE

ESTREMI DELLA

PUBBLICAZIONE

ISSN/ISBN

Articolo

La Ferla M, Mercatanti A, Rocchi G, Lodovichi S, Expression of human poly (ADP-ribose) polymerase 1

in Saccharomyces

Mutat Res. 2015 Apr;774:14-24.

(5)

5

Cervelli T, Pignata L, Caligo MA, Galli A. cerevisiae: Effect on survival, homologous recombination and identification of genes involved in intracellular localization

Articolo

Maresca L, Spugnesi L, Lodovichi S, Cozzani C, Naccarato AG, Tancredi M, Collavoli A, Falaschi E, Rossetti E, Aretini P, Cervelli T, Galli A, Caligo MA. MSH2 role in BRCA1-driven tumorigenesis: A preliminary study in yeast and in human tumors from

BRCA1-VUS carriers.

Eur J Med Genet. 2015

Oct;58(10):531-9.

Articolo

Lodovichi S, Vitello M, Cervelli T, Galli A. Expression of cancer related BRCA1 missense variants decreases MMS-induced recombination in Saccharomyces cerevisiae without altering its nuclear

localization.

Cell Cycle. 2016 Oct

17;15(20):2723-31.

Articolo

Mercatanti A, Lodovichi S, Cervelli T, Galli A. CRIMEtoYHU: a new web tool to develop yeast-based functional assays for

characterizing cancer-associated missense variants.

FEMS Yeast Res. 2017

Dec 1;17(8)

PUBBLICAZIONI (in corso di pubblicazione) / PUBLICATIONS (submitted but not yet published)

TIPOLOGIA

PUBBLICAZIONE

(articolo, proceeding, monografia, edizione fonti…)

TYPOLOGY:

( article, proceeding, monography, source edition…)

ALTRI AUTORI

/ COAUTHORS

TITOLO DELLA

PUBBLICAZIONE

TITLE

ESTREMI DELLA PUBBLICAZIONE

(rivista, editore, convegno, altro)

PUBLICATION DETAILS

(journal title, publishing company,

conference title and so on)

Articolo

Lodovichi S,

Mercatanti A, Cervelli T,

Galli A,

Computational analysis of data from a genome-wide screening identifies new

PARP1 functional interactors as potential new

therapeutic targets

Cancer Management and

Research

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6 Articolo

Cervelli T, Monaco R, Tancredi M, Lodovichi S, Spugnesi L, Falaschi E, Landucci E, Gadducci A, Roncella M, Naccarato AG, Caligo MA, Maresca L, Lorenzoni A, Zavaglia K, Congregati C

Characterization of BRCA1-induced genomic instability and identification of a novel PARP1 interactor

1

REPORT SULLE ATTIVITÀ SVOLTE

REPORT ON THE ACTIVITIES UNDERTAKEN

Corso di dottorato / PhD Program _____Scienze Cliniche e Traslazionale_____

Curriculum (se previsto / if applicable) _______________________________

Cognome / Family Name _____Lodovichi _____

Nome / Name _____Samuele_____

Data nascita / Date of Birth _____19/08/1987_____

Luogo nascita / Place of Birth _____Cecina_____

Data di rilascio del titolo / Date of issue of the certificate ________________________

Eventuale valutazione (se prevista) / Subsequent evaluation (if applicable) __________

Supervisore / Supervisor _____Alvaro Galli_____

Commissione di esame finale (Nome, cognome e ente di afferenza) / Final exam board (Name,

Family Name and relevant department) ______________________________________________

ATTIVITÀ FORMATIVE / FORMATIVE ACTIVITIES

I anno di corso / I course year (anno accademico / academic year 2014/15)

2

II anno di corso / II course year (anno accademico / academic year 2015/16)

ACTIVITIES CARRIED OUT AND RESULTS

3

III anno di corso / III course year (anno accademico / academic year 2016/17)

ACTIVITIES CARRIED OUT AND RESULTS

Da 20/02/2017 a

12/08/2017

Moffitt Cancer Center,

Tampa, Florida.

Supervisor: Dr. Alvaro N.

Monteiro

TITOLO DELLA TESI / TITLE OF THE PHD THESIS

Characterization of BRCA1-induced genomic instability and identification of a novel PARP1

interactor

4

PROGETTO DI RICERCA/RESEARCH PROJECT

Based on results that expression of BRCA1 cancer related missense variants increases spontaneous

homologous recombination in diploid strain of the yeast Saccharomyces cerevisiae, in this study we

used this model organism to study contribution of BRCA1 partners in genomic instability caused by

BRCA1 pathogenic variants expression. Then I analyzed effect of BRCA1 expression on gene

reversion in phase-arrested cells, in order to eventually relate these events increases to a particular

phase of the cell cycle, therefore giving indication about its pathogenicity to a phase-specific

mechanism. I also analyzed recombination induction of DNA damage agent MMS in cell expressing

pathogenic variants of BRCA1 and new candidates PARP1 interactors starting from a wide-genome

yeast screening data.

CONVEGNI, WORKSHOP E SEMINARI IN ITALIA E ALL’ESTERO/ CONFERENCES, WORKSHOPS,

SEMINARSATTENDED IN ITALY AND ABROAD

Lodovichi S, La Ferla M, Rocchi G, Mercantanti A, Cervelli T, Caligo MA e Galli A. “A genome-wide screening

in yeast identifies genes potentially involved in PARP1 regulation” at HEREDITARY BREAST & OVARIAN

CANCER congress (January 2015), Bari, Italy.

Lodovichi S, Vitello M, Cervelli T, Galli A. “Intracellular localization and cell cycle effect of cancer related

BRCA1 missense variants in yeast” 27th International Congress on Yeast Genetics and Molecular Biology,

6-12 September 2015, Levico Terme, Trento, Italy

Lorenzoni A, Lodovichi S, Cervelli T, Galli A. “Cell cycle dependency of BRCA1-induced gene reversion in

Saccharomyces cerevisaie” FISV (Federazione Italiana Scienze della Vita) 2016 XIV Congress, Rome, Italy,

20-23 September 2016

(No poster)

AACR Annual Meeting 2017, April 1 - 5 2017, Walter E. Washington Convention Center, Washington, D.C.,

USA

EVENTUALE ATTIVITÀ DI RICERCA IN AZIENDA / SUBSEQUENT RESEARCH ACTIVITIES IN

COMPANIES

PUBBLICAZIONI (N.B. depositate in ARPI) / PUBLICATIONS (Note: Publications must be stored in

ARPI

TIPOLOGIA

PUBBLICAZIONE

ALTRI

AUTORI

COAUTHORS

TITOLO DELLA

PUBBLICAZIONE

TITLE

ESTREMI DELLA

PUBBLICAZIONE

ISSN/ISBN

Articolo

5

Articolo

Eur J Med Genet. 2015

Oct;58(10):531-9.

Articolo

Cell Cycle. 2016 Oct

17;15(20):2723-31.

Corso di dottorato / PhD Program _Scienze Cliniche e Traslazionale_

Cognome / Family Name _Lodovichi _

Nome / Name _Samuele_

Data nascita / Date of Birth _19/08/1987_

Luogo nascita / Place of Birth _Cecina_

Supervisore / Supervisor _Alvaro Galli_

Data, _15.03.18_________