PEZZOTTA ALEX

Alex Pezzotta
Type A Fixed term Researcher
SSD BIOS 10/A
Department of Biotecnologie Mediche e Medicina Traslazionale (BIOMETRA)
LITA, Via Fratelli Cervi 93, 20054, Segrate (MI)
Phone +39-02-50330358

ORCID: 0000-0003-1788-5880

Education

PhD in Experimental medicine XXXIV cycle
Università degli Studi di Milano; 18 May 2022
Thesis title: “Hedgehog/HDAC6 inhibition and chemotherapy: assessment of new drug combination in acute myeloid leukemia”. Tutor: Prof. Anna Pistocchi; supervisor: Dr. Alberto Rissone

Professional License to the title of Biologist
Università degli studi di Pavia; July 30, 2020

Master’s degree in Biology applied to biomedical research
Università degli Studi di Milano; 14 December 2016
Mark: 110/110 cum laude
Thesis title: “Study the role of the Six transcriptional factors in the development of the vascular system in zebrafish: analyses of mutants and morphants”. Tutor: Dr. Monica Beltrame; co-tutor: Dr. Silvia Moleri

Degree in Biological Sciences
Università degli Studi di Milano; 02 October 2014
Mark: 104/110
Tutor: Prof. Franco Cotelli

Research and professional experience

Type A researcher (RTD-A)
01 october 2023 – ongoing
Dept. Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano

Type A post-doc fellowship
01 June 2022- 30 September 2023
Dept. Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano
Research line: “Identification and functional study of genes and genetic mechanisms involved in human pathologies" Tutor: Prof. Anna Pistocchi

PhD scholarship in Experimental Medicine XXXIV cycle
01 November 2018 – 17 May 2022
Dept. Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano
Research line: “Hedgehog/HDAC6 inhibition and chemotherapy: assessment of new drug combination in acute myeloid leukemia”. Tutor: Prof. Anna Pistocchi

“Promising Young” Scholarship
01 January 2018 – 01 November 2018
Dept. Biotecnologie Mediche e Medicina Traslazionale¸ Universita degli Studi di Milano
Research line: “Hdac8 and cohesins: promising therapeutic targets for myeloid malignancies” Tutor: Prof. Anna Pistocchi

“Promising Young” Scholarship
February 2017- October 2017
Dept. Bioscienze¸ Universita degli Studi di Milano
Research line: “HCN protein interactors: an in vivo approach” Tutor: Prof. Anna Moroni

Master’s degree thesis
October 2015 - 14 December 2016
Dept. Bioscienze¸ Universita degli Studi di Milano
Research line: “zebrafish morphants and mutants” Tutor: Dr. Monica Beltrame

Training courses

Ethics and conception of projects, modules 9, 10, 11, ministerial decree 5 august 2021 - single edition.
30 November 2023
Experimental Zooprophylactic Institute of Lombardy and Emilia-Romagna
Objectives: Veterinary healthcare. Activities at the animal facilities. Plant health
Acquisition of technical-professional skills: The course is aimed in particular at those who conceive research projects using laboratory animals (art.23 of Legislative Decree 26/2014 functions b)), but can be attended by all the figures foreseen by art.23 of Legislative Decree 26 /2014 functions a) b) c) d), and as required by the Ministerial Decree of 5 August 2021 includes the modules: module 9 Ethics, animal welfare and Three Rs (level 2); Module 10 Design of procedures and projects (level 1 – statistics), Module 11 Design of procedures and projects (level 2)
Course duration: 6 hours (9 ECM)
Accreditation ID: 373214
Scientific manager: Dr. Guerino Lombardi

Using fish in research - 1 "Zebrafish, Peociliidae, other fish (Medaka, , Nothobranchius,etc.), Modules 3.1, 4, 5 and 7 Ministerial Decree 5 August 2021;
30 November 2023
Experimental Zooprophylactic Institute of Lombardy and Emilia-Romagna
Objectives: Veterinary healthcare. Activities in animal facilities. Vegetable health
Acquisition of system skills: The course is aimed at all the expected figures from art.23 of Legislative Decree 26/2014 functions a) b) c) d) as provided for by the Ministerial Decree of 5 August 2021 and contemplates the Modules: Module 3.1 Basic Appropriate Biology -Species Specific (Theory); module 4 Care,animal health and management - species specific (theory); module 5 Pain recognition,of suffering and distress - species specific; Humane methods of suppression (theory);module 7 Minimally invasive procedures without anesthesia - species specific (theory)
Course duration: 13 hours (19.5 ECM)
Accreditation ID: 380724
Scientific manager: Dr. Livia d’Angelo

National legislation and ethics level 1, modules 1 and 2, DM 5 August 2021 - 1st Edition
28 February 2023
Experimental Zooprophylactic Institute of Lombardy and Emilia-Romagna
Objectives: Veterinary healthcare. Activities in animal enclosures. Vegetable health
Acquisition of system skills: The course is aimed at all the figures envisaged by article 23 of Legislative Decree 26/2014 functions a) b) c) d) as required by the Ministerial Decree of August 5, 2021 and contemplates modules 1 and 2: National legislation; Ethics, animal welfare and the Three Rs (level 1).
Course duration: 5 hours (7.5 ECM)
Accreditation ID: 372523
Scientific manager: Dr. Andrea Cacciamali

Zebrafish as a Model Organism: In Vitro and In Vivo Experimental Approaches in Scientific Research - Single Edition.
19 February 2023
Experimental Zooprophylactic Institute of Lombardy and Emilia-Romagna
Objectives: Technological innovation: evaluation, improvement of management processes of biomedical, chemical, physical and medical device technologies. Health Technology Assessment.
Acquisition of technical-professional skills: The event aims to provide an in-depth overview of the use of the Zebrafish model system in scientific experimentation. Specifically, the topic addressed will develop topics related to the management and housing of zebrafish, the comparison with other experimental models in use and the various applications in the field of biomedical research. These approaches represent one of the new frontiers in both veterinary and human medicine Technological innovation: evaluation, improvement of management processes of biomedical, chemical, physical and medical device technologies. Health Technology Assessment.
Course duration: 4 hours (4 ECM)
Accreditation ID: 373179
Scientific manager: Dr. Guerino Lombardi

Introduction to animal experimentation.
27-29 September 2017
IRCCS- Pharmacological Research Institute "M. Negri" of Milan.
Objectives: animal facilities management, legislation and ethics for the use of animal models
Course duration: 2 days
Scientific manager: Dr. Gianluca Grignaschi

Teaching assignment

A.A. 2024/2025
Laboratorio di Metodologie Cellulari e Molecolari
Biologia, Chimica e biochimica generale
Scienze di base

A.A. 2023/2024
Genetics
Laboratorio di Metodologie Cellulari e Molecolari

(Competition winner art45 ID1027) A.A 2021/2022
Tutoring activities in "Cellular and molecular methodologies course”
Total hours of assignment: 60
Three-year Degree Course in Medical Biotechnology
Università degli Studi di Milano
Department of Biotecnologie Mediche e Medicina Traslazionale

(Competition winner art45 ID1130) A.A. 2021/2022
Tutoring activities in the course “From organism to molecules: transcription factors and regulation of development and differentiation”
Total hours of assignment: 27
Three-year degree course in Biological Science
Università degli Studi di Milano
Department of Bioscienze

(Competition winner art45 ID858) A.A 2020/2021
Tutoring activities in "Cellular and molecular methodologies course”
Total hours of assignment: 30
Three-year Degree Course in Medical Biotechnology
Università degli Studi di Milano
Department of Biotecnologie Mediche e Medicina Traslazionale

(Competition winner art45 ID974) A.A. 2020/2021
Tutoring activities in the course “From organism to molecules: transcription factors and regulation of development and differentiation”
Total hours of assignment: 18
Three-year degree course in Biological Science
Università degli Studi di Milano
Department of Bioscienze

(Competition winner art45 ID772) A.A 2019/2020
Tutoring activities in the course “From organism to molecules: transcription factors and regulation of development and differentiation”
Total hours of assignment: 18
Three-year degree course in Biological Science
Università degli Studi di Milano
Department of Bioscienze

(Competition winner art45 ID657) A.A. 2019/2020
Tutoring activities in "Cellular and molecular methodologies course”
Total hours of assignment: 32
Three-year Degree Course in Medical Biotechnology
Università degli Studi di Milano
Department of Biotecnologie Mediche e Medicina Traslazionale

(Competition winner art45 ID562) A.A. 2018/2019
Tutoring activities in the course “From organism to molecules: transcription factors and regulation of development and differentiation”
Total hours of assignment: 16
Three-year degree course in Biological Science
Università degli Studi di Milano
Department of Bioscienze

Thesis Supervisor

Elisabetta Galloro bachelor’s degree thesis supervisor
A.A. 2023/2024
Bachelor's degree in Medical Biotechnology
Università degli Studi di Milano
Thesis title: “Analysis of the inflammatory profile of dystrophic zebrafish embryos after treatment with HDAC8 and SIRT1 modulators”.

Jona Xhymerti's master thesis co-supervisor
A.A. 2023/2024
Master's degree in medical biotechnology and molecular medicine
Università degli Studi di Milano
Thesis title: “Safety and efficacy profiling of new synthetic HDAC6 inhibitors for the treatment of Acute Myeloid Leukemia using zebrafish as an in vivo model”.

Sabrina Carbone's master thesis co-supervisor
A.A. 2021/2022
Master's degree in medical biotechnology and molecular medicine
Università degli Studi di Milano
Thesis title: “Investigating the role of Hh and HDAC6 inhibition on the autophagic process: a new therapeutic strategy to treat glioblastoma multiforme patients”.

Miriana Rizzo bachelor’s degree thesis co-supervisor
A.A. 2021/2022
Bachelor's degree in Medical Biotechnology
Università degli Studi di Milano
Thesis title: “Analysis of the effect of primary ciliogenesis modulation on Hedgehog and HDAC6 signaling pathways in the zebrafish model”.

Gaia Galassi bachelor’s degree thesis co-supervisor
A.A. 2020/2021
Bachelor's Degree in Medical Biotechnology
Università degli Studi di Milano
Thesis title: "In vitro and in vivo characterization of the effects of Hedgehog and HDAC6 inhibition for the treatment of acute myeloid leukemia".

Paola Ghislanzoni bachelor’s degree thesis co-supervisor
A.A 2017/2018
Bachelor's Degree in Medical Biotechnology
Università degli Studi di Milano
Thesis title: "Analysis of the role of genea in myelin differentiation in the zebrafish (Danio rerio) model".7

Scientific publications (chronological order)
Carullo G, Rossi S, Giudice V, Pezzotta A, Chianese U, Scala P, Carbone S, Fontana A, Panzeca G, Pasquini S, Contri C, Gemma S, Ramunno A, Saponara S, Galvani F, Lodola A, Mor M, Benedetti R, Selleri C, Varani K, Butini S, Altucci L, Vincenzi F, Pistocchi A, Campiani G. Development of Epigenetic Modifiers with Therapeutic Potential in FMS-Related Tyrosine Kinase 3/Internal Tandem Duplication (FLT3/ITD) Acute Myeloid Leukemia and Other Blood Malignancies. ACS Pharmacol Transl Sci. 2024 Jul 2;7(7):2125-2142. doi: 10.1021/acsptsci.4c00208. PMID: 39022363; PMCID: PMC11249625.

Brix A, Belleri L, Pezzotta A, Pettinato E, Mazzola M, Zoccolillo M, Marozzi A, Monteiro R, Del Bene F, Mortellaro A, Pistocchi A. ADA2 regulates inflammation and hematopoietic stem cell emergence via the A2bR pathway in zebrafish. Commun Biol. 2024 May 22;7(1):615. doi: 10.1038/s42003-024-06286-3. PMID: 38777862; PMCID: PMC11111730.

Pezzotta A, Brioschi L, Carbone S, Mazzoleni B, Bontempi V, Monastra F, Mauri L, Marozzi A, Mione M, Pistocchi A, Viani P. Combined Inhibition of Hedgehog and HDAC6: In Vitro and In Vivo Studies Reveal a New Role for Lysosomal Stress in Reducing Glioblastoma Cell Viability. Int J Mol Sci. 2023 Mar 17;24(6):5771. doi: 10.3390/ijms24065771. PMID: 36982845; PMCID: PMC10051748.

Pezzotta A, Gentile I, Genovese D, Totaro MG, Battaglia C, Leung AY, Fumagalli M, Parma M, Cazzaniga G, Fazio G, Alcalay M, Marozzi A, Pistocchi A. HDAC6 inhibition decreases leukemic stem cell expansion driven by Hedgehog hyperactivation by restoring primary ciliogenesis. Pharmacol Res. 2022 Sep;183:106378. doi: 10.1016/j.phrs.2022.106378. Epub 2022 Jul 30. PMID: 35918044.

Federico S, Khan T, Fontana A, Brogi S, Benedetti R, Sarno F, Carullo G, Pezzotta A, Saraswati AP, Passaro E, Pozzetti L, Papa A, Relitti N, Gemma S, Butini S, Pistocchi A, Ramunno A, Vincenzi F, Varani K, Tatangelo V, Patrussi L, Baldari CT, Saponara S, Gorelli B, Lamponi S, Valoti M, Saccoccia F, Giannaccari M, Ruberti G, Herp D, Jung M, Altucci L, Campiani G. Azetidin-2-one-based small molecules as dual hHDAC6/HDAC8 inhibitors: Investigation of their mechanism of action and impact of dual inhibition profile on cell viability. Eur J Med Chem. 2022 Aug 5;238:114409. doi: 10.1016/j.ejmech.2022.114409. Epub 2022 May 1. PMID: 35551034.

Pradella D, Deflorian G, Pezzotta A, Di Matteo A, Belloni E, Campolungo D, Paradisi A, Bugatti M, Vermi W, Campioni M, Chiapparino A, Scietti L, Forneris F, Giampietro C, Volf N, Rehman M, Zacchigna S, Paronetto MP, Pistocchi A, Eichmann A, Mehlen P, Ghigna C. A ligand-insensitive UNC5B splicing isoform regulates angiogenesis by promoting apoptosis. Nat Commun. 2021 Aug 11;12(1):4872. doi: 10.1038/s41467-021-24998-6. PMID: 34381052; PMCID: PMC8358048.

Mazzola M, Pezzotta A, Fazio G, Rigamonti A, Bresciani E, Gaudenzi G, Pelleri MC, Saitta C, Ferrari L, Parma M, Fumagalli M, Biondi A, Cazzaniga G, Marozzi A, Pistocchi A. Dysregulation of NIPBL leads to impaired RUNX1 expression and haematopoietic defects. J Cell Mol Med. 2020 Jun;24(11):6272-6282. doi: 10.1111/jcmm.15269. Epub 2020 Apr 23. PMID: 32323916; PMCID: PMC7294146.

Mazzola M, Deflorian G, Pezzotta A, Ferrari L, Fazio G, Bresciani E, Saitta C, Ferrari L, Fumagalli M, Parma M, Marasca F, Bodega B, Riva P, Cotelli F, Biondi A, Marozzi A, Cazzaniga G, Pistocchi A. NIPBL: a new player in myeloid cell differentiation. Haematologica. 2019 Jul;104(7):1332-1341. doi: 10.3324/haematol.2018.200899. Epub 2019 Jan 10. PMID: 30630974; PMCID: PMC6601076.

Ferrari L, Bragato C, Brioschi L, Spreafico M, Esposito S, Pezzotta A, Pizzetti F, Moreno-Fortuny A, Bellipanni G, Giordano A, Riva P, Frabetti F, Viani P, Cossu G, Mora M, Marozzi A, Pistocchi A. HDAC8 regulates canonical Wnt pathway to promote differentiation in skeletal muscles. J Cell Physiol. 2019 May;234(5):6067-6076. doi: 10.1002/jcp.27341. Epub 2018 Sep 24. PMID: 30246374.

Pezzotta A, Mazzola M, Spreafico M, Marozzi A, Pistocchi A. Enigmatic Ladies of the Rings: How Cohesin Dysfunction Affects Myeloid Neoplasms Insurgence. Front Cell Dev Biol. 2019 Feb 27;7:21. doi: 10.3389/fcell.2019.00021. PMID: 30873408; PMCID: PMC6400976.

Conferences
Seminar of the of the BIOMETRA dept, Università degli studi di Milano; 21 march 2024. Title:”HDAC6 and HDAC8 in Acute Myeloid leukemia:lessons from zebrafish”; oral presentation.
4th Italian zebrafish meeting (ZFIM),07-09 February 2024., University of Palermo. Title: “Hedgehog and HDAC6 in cancers:dissection of dysregulated biological mechanisms and potential therapeutic treatments”; oral presentation.
GTC, Gene and Cell Therapy conference, Virtual (London), 12-13 december 2023. Title: “HDAC6 inhibition decreases leukemic stem cell expansion driven by Hedgehog hyperactivation by restoring primary ciliogenesis”; invited speaker for oral presentation.
SIGU, Italian society of genetics, Rimini (Italy); 04-06 October 2023. Attendance
MyDEV, Università degli studi di Milano; 19 may 2023. Title: “Combined Inhibition of Hedgehog and HDAC6: In Vitro and In Vivo Studies Reveal a New Role for Lysosomal Stress in Reducing Glioblastoma Cell Viability”; poster
Workshop of the BIOMETRA dept, Università degli studi di Milano. 20 September 2022. Title: “The tale of HDAC6 and Hedgehgog in glioblastoma: one year later”. Oral presentation
Third Italian zebrafish meeting (ZFIM),Università degli studi di Napoli, 20 September 2022 .Title: “Targeting Hedgehog and HDAC6 in acute myeloid leukemia in in vitro and zebrafish models”. Oral presentation
Workshop of the BIOMETRA dept, Università degli studi di Milano; 27 September 2021. Title: “Exploring the crosstalk of sphingolipid signaling with Hedgehog and HDAC6 pathways in glioblastoma”. Oral presentation
Virtual 11th European zebrafish meeting, 26-27 October 2020. Title: “A new candidate gene involved in nervous system myelination: functional in-vivo validation using a zebrafish model system”. Poster
Workshop of the BIOMETRA dept, Università degli studi di Milano ;28 September 2020, University of Milan. Attendance
Workshop of the BIOMETRA dept, Università degli studi di Milano 24 September 2019. Title: “NIPBL: a new player in myeloid cell differentiation”. Short Oral presentation (awarded)
ABCD conference, Bologna (Italy), 19-21 September 2019. Title: “A new candidate gene involved in nervous system myelination: functional in-vivo validation using a zebrafish model system”. Poster
MyDev, Università degli studi di Milano, 19 May 2019. Title: “NIPBL: a new player in myeloid cells differentiation. Oral presentation
Second Italian zebrafish meeting (ZFIM), Università degli studi di Pisa (Italy), 30 January- 1 February 2019. Title: “NIPBL: a new player in myeloid cells differentiation. Oral presentation.
Second Italian zebrafish meeting (ZFIM), Università degli studi di Pisa (Italy), 30 January- 1 February 2019.Title: “A new sox18 mutant supports evolutionary conservation in early lymphatic development from fish to mammals”. Poster
Workshop of the BIOMETRA dept, Università degli studi di Milano. 24 September 2018. Title: “A new candidate gene involved in nervous system myelination: functional in-vivo validation using a zebrafish model system”. Poster
Neuronest, Università degli studi di Milano, 27 March 2018. Title: “A new candidate gene involved in nervous system myelination: functional invivo validation using a zebrafish model system”. Poster
First Italian zebrafish meeting (ZFIM) Università degli studi di Padova (Italy). 2-3 febbraio 2017. Title: “Sox18: on morphants and mutants”. Poster