DE LUCA Michele

CURRICULUM VITAE

MICHELE DE LUCA, M.D.

ORCID ID orcid.org/0000-0002-0850-8445
ResearcherID N-5883-2014
Scopus Author ID 56082113500
H-INDEX (Scopus): 54
Citations (Scopus): 13.341

CURRENT POSITION
Full Professor of Biochemistry, University of Modena and Reggio Emilia, Modena, Italy.
Director, Centre for Regenerative Medicine "Stefano Ferrari" (CMR), Dept. of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
Director, Interdepartmental Centre for Stem Cells and Regenerative Medicine (CIDSTEM) University of Modena and Reggio Emilia, Modena, Italy
Coordinator, PhD Program in Molecular and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy


EDUCATION
1984: Specialty in Endocrinology, cum laude, University “La Sapienza” , Rome Medical School
1980: M.D., cum laude, University of Catania, Catania Medical School.


PROFESSIONAL EXPERIENCE
2010-present: Director, Interdepartmental Centre for Stem Cells and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
2008-present: Director, Centre for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia, Modena, Italy
2008-2023: Scientific Director, Cofounder and QP, Holostem Terapie Avanzate S.r.l., Modena, Italy
2004-present: Full Professor of Biochemistry, Department of Life Science, University of Modena and Reggio Emilia, Modena, Italy
2002-2007: Scientific Director, Veneto Eye Bank Foundation, Venice, Italy
1996-2002: Head, Laboratory of Tissue Engineering, I.D.I., Istituto Dermopatico dell'Immacolata, Roma, Italy
1992-1995: Deputy Head, Laboratory of Cell Differentiation, National Institute for Cancer Research, Genova, Italy
1986-1992: Senior Investigator, Laboratory of Cell Differentiation, National Institute for Cancer Research, Genova, Italy
1985: Visiting scientist at the Department of Physiology and Biophysics, Harvard Medical School (HMS), Boston, MA, USA
1982-1985: Fogarty Fellow, Section on Biochemistry of Cell Regulation, Laboratory of Biochemical Pharmacology, National Institutes of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK), National Institutes of Health (NIH), Bethesda, MD, USA


SUMMARY AND ESSENCE OF SCIENTIFIC ACTIVITY
Michele De Luca has dedicated most of his scientific activities to translational medicine (Stem Cell Reports. 2018).
He is recognised as leading scientist in human squamous epithelial stem cell biology aimed at the development of epithelial stem cell-mediated cell therapy and gene therapy.
Following on early work on the use of human epidermal stem cell cultures in life-saving treatment of massive full-thickness burns (reviewed in Regen. Med. 2006), Michele De Luca was first to establish human urethral stem cell culture aimed at urethral regeneration in posterior hypospadias (N. Engl. J. Med. 1990).
De Luca and his historic collaborator Graziella Pellegrini developed human limbal stem cell culture (J. Cell Biol. 1999) for corneal regeneration in patients with severe limbal stem cell deficiency (Lancet 1997; N. Engl. J. Med 2010; Regen. Med. 2013, Stem Cells Transl Med. 2018). This treatment leads to recovery of normal vision and is now used worldwide. In February 2015 such cultures were formally approved as an Advanced Therapy Medicinal Product by EMA, which registered them under the name of Holoclar. Holoclar is the first stem cell-based therapy approved in Europe and EMA has indicated it amongst the most relevant achiements in the field in the last 20 years.
They have characterised molecular mechanisms regulating long term proliferative potential, clonal evolution and self-renewal of epithelial stem cells. In particular, they shed light on the role of p63 (different isoforms) and c/EBPδ in regulating the proliferative potential and the self-renewal of human corneal stem cells, respectively (PNAS 2001, 2005; J. Cell Biol. 2007). Notably, their work demonstrated that the clinical success of limbal stem cultures is dependent on a discrete number of stem cells identified as holoclones expressing the ΔNα isoform of p63 (N. Engl. J. Med. 2010, TMM 2011, Regen. Med. 2013).
Michele De Luca is also pioneering ex-vivo epithelial stem cell-mediated gene therapy for genetic skin diseases. He coordinated the first successful clinical trial to treat junctional epidermolysis bullosa (JEB) (Nat. Med. 2006; Stem Cell Rep. 2014; J. Invest. Dermatol, 2017; Nature, 2017, Cell Rep. 2019) and his coordinating clinical trials for other forms of EB.
JEB is a severe, often lethal genetic disease caused by mutations in genes encoding the basement membrane component laminin-332. Surviving JEB patients develop chronic skin and mucosa wounds, which impair their quality of life and lead to skin cancer. De Luca has recently reported life-saving regeneration of the entire, fully functional, epidermis on a 7-year-old child suffering from a devastating, life-threatening form of JEB (Nature, 2017). Using integrations as clonal genetic marks, he has shown that the vast majority of epidermal TA progenitors are progressively lost within a few months after grafting and the regenerated epidermis is indeed sustained only by a limited number of long-lasting, self-renewing stem cells. This notion argues against a model positing the existence of a population of equipotent epidermal progenitors that directly generate differentiated cells during the lifetime of the animal and fosters a model where specific stem cells persist during the lifetime of the human and contribute to both renewal and repair by giving rise to pools of progenitors that persist for various periods of time, replenish differentiated cells and make short-term contribution to wound healing (Nature, 2017). Based on this notion and on the corneal data (N. Engl. J. Med 2010) De Luca and Pellegrini established that the essential feature of any cultured epithelial grafts is the presence (and preservation) of an adequate number of holoclone-forming cells. Their work thus provides a blueprint that can be applied to other stem cell-mediated ex vivo cell and gene therapies (N&V Nature 2010, Nat. Cell Biol. 2019, Cold Spring Harb Perspect Biol. 2019).


Michele De Luca is internationally recognised for his experience in stem cell therapy and contributed to two reports by the International Society for Stem Cell Research, dealing with new guidelines for responsible translational stem cells research (Cell Stem Cell 2008, 2009).
Michele De Luca, in collaboration with several clinicians, have treated:
• Approximately 400 patients with massive skin burns (life-saving)
• Over 400 patients with massive ocular burns (restoration of vision)
• Approximately 100 patients with stable vitiligo and piebaldism
• 170 patients with oral mucosa defects
• 18 patients with posterior hypospadias
• 3 patients with JEB (Italy, Austria and Germany)
• current PhaseI/II clinical trials of ex vivo gene therapy of Epidermolysis Bullosa (24 patients enrolled in Europe)
by means of cultured and highly characterized epithelial stem cells.

AWARDS AND RECOGNITIONS
National and international awards
2020 - Fondation Louis-Jeantet, Louis-Jeantet Prize (co-awarded with Graziella Pellegrini)
2019 - New York Academy of Science & Takeda Pharmaceuticals, “Innovator in Science Award 2019”
2018 - International Prize “Lombardia è ricerca” (co-awarded with Tobias Hirsch and Graziella Pellegrini)
2018 - Royan Institute (Teheran), Kazemi Award for Research Excellence in Bio-Medicine
2018 - EURORDIS, Black Pearl Award - Scientific Award (co-awarded with Tobias Hirsch)
2018 - ISSCR, Award for innovation (co-awarded with Graziella Pellegrini)
2017 - The Niche (Knoepfler Lab Blog Stem Cell Blog), Stem Cell Person of the Year Award
2016 - Prix Galien Netherlands 2016 for Holoclar
2016 - Prix Galien United Kingdom 2016 for Holoclar
2016 - UNICEF, Premio Ragno d'Oro
2015 - “Menzione speciale all’innovazione” for Holoclar, Premio Galeno Italia
2015 - Premio Luigi Coppola - Città di Gallipoli
2015 - Comune di Modena, Premio Città di Modena - "Bonissima" awarded by Centre for Regenerative Medicine “Stefano Ferrari”
2015 - Comune di Modena, Premio Città di Modena - "Bonissima" awarded by Holostem Terapie Avanzate
2015 - MIT Technology Review Italia, “Smart & Disruptive Companies 2015” Award to Holostem Terapie Avanzate
2014 - ISSCR, Public Service Award (co-awarded with Paolo Bianco and Elena Cattaneo)
2014 - Comune di Milano, Premio Ambrosoli
2014 - Comune di Padova, Menzione Speciale della giuria scientifica del Premio Galileo per la Divulgazione Scientifica (co-awarded with Paolo Bianco, Elena Cattaneo and Gilberto Corbellini)
2008 - Debra Italia Onlus, Premio Farfalla d'argento
Recognitions
Life member of the New York Academy of Science
Fellow of Accademia Nazionale dei Lincei
Member of the European Molecular Biology Oragnization (EMBO)
Honorary Member of Associazione degli allievi del Collegio Ghisleri di Pavia
Fellow of Accademia nazionale di Scienze, Lettere e Arti di Modena
Private meeting with the Italian President Sergio Mattarella, Rome, 16 May 2018
Honorary member of the patients’ association Debra Südtirol Alto Adige

PATENTS
De Luca M., Pellegrini G. Usi terapeutici di lembi di cellule geneticamente modificate. National patent application n.102017000104587 OC/133447
Pellegrini G., Alessandrini A., De Luca M., In vitro method for producing a flap of genetically modified cells on fibrin substrate, Patent Application n. 102017000094210, Aug. 17 2017.
De Luca M. and Pellegrini G., In vitro reconstituted sheets of human corneal epithelium and method of producing the same, EP Patent 1451302, May 28, 2008
De Luca M. and Pellegrini G., Reconstructed laminae of human epithelium corneae and method of producing the same, US Patent 6,610,538, Aug. 26, 2003
Geraci G., De Rosa M., Rossi M., Cancedda R., De Luca M. and Pellegrini G., Cryoprotective acqueous solution useful for the preservation of in vitro cultured epithelial cells, EP Patent 0671877, Aug. 19, 1998
Geraci G., De Rosa M., Rossi M., Cancedda R., De Luca M. and Pellegrini G., Cryoprotective acqueous solution useful for the preservation of in vitro cultured epithelial sheets, US Patent 5,670,308, Sep. 23, 1997
Cancedda R. and De Luca M., Cryopreserved in vitro cultured epithelial tissue and method, US Patent 5,298,417, Mar. 29 1994
Cancedda R. and De Luca M., Method for preserving transplantable sheets of epithelium cultured in vitro, EP Patent 0296475, Aug 26 1992
Cancedda R. and De Luca M., Metodo per la preservazione di fogli trapiantabili di epitelio coltivato in vitro vitale, IT Patent 1207525, May 25, 1989.

SCIENTIFIC SOCIETIES AND COMMITMENTS
2023-: ISSCR, member of the Advisory Board
2020-: NSC-Reconstruct, Member of the Scientific and Ethical Advisory Board
2019-: Life member of the New York Academy of Sciences
2019-: SkinTERM, Member of the Advisory Board
2019-: Osservatorio Terapie Avanzate, Member of Scientific Advisory Board
2018-: Member of the External Advisory Board Great Ormond Street Hospital “GOSH” Bio-medical Research Center (BRC)
2018-: Member of the Advisory Board of SkinTERM
2018-: Fellow of the Accademia dei Lincei
2018-: EMBO Member
2017-: Member of the External Advisory Board (EAB) at NIHR Great Ormond Street Hospital Biomedical Research Centre
2014-: Fellow of the Accademia Nazionale di Scienze, Lettere e Arti di Modena
2012-: Member of the Scientific Advisory Board, REVIVE (Stem Cells in Regenerative Biology and Medicine Consortium)
2008: Member of the ISSCR International Committee on Clinical Translation
2008-: Member of External Advisory Board, Skin Diseases Research Core Center, University of Colorado Denver, Medical School
2008-: Member of Board of Directors, Holostem Terapie Avanzate S.r.l., Modena, Italy
2008-: Funding Member of Stem Cell Research Italy and member of the Techinical-Scientific Committe
2007: Member of International Society for Stem Cell Research (ISSCR) Task Force on Clinical Translation of Stem Cells.
2007-: Member of the Editorial Academy of International Journal of Molecular Medicine.
2005-2007: Member of Working Group on Engeneered Cells of Istituto Superiore di Sanità-Centro Nazionale Trapianti.
2004-2007: Member of Regional Technical Scientific Committee of Regional Laboratory (Veneto) of Stem Cells (Cell Factory).
2004-2007: Member of the International Advisory Board of National Epidermolysis Bullosa Network, Germany.
2004-: ISSCR Member
2003: Member of the Scientific Committee of ESGT (European Society of Gene Therapy)
2002-: Member of the American Association for the Advancement of Science
2002-2004: Member of the Scientific Council of “TEGO Science”, Seoul, South Korea
2001-2008: Member of the National Commission of Health Ministry for Stem Cells
2001-2003: Member of the Scientific Council of ISOTIS, Tissue Engineers”, Amsterdam, The Netherlands.
2001-2002: Member of the Scientific Committee of “Banca degli Occhi dell’Ente Ospedaliero S. Giovanni-Addolorata”, Rome, Italy
2000-: Founding member of the International Ocular Surface Society
2000-: Reviewer of various International Scientific Magazines including Cell, Nature, N. Eng. J. Med., J. Cell Biol., Proc. Natl. Acad. Sci. USA.
1999-: Member of Scientific Council of “J-TEC”, Gamagori, Japan
1999-2002: Member of the Board of the Italian Society for Cell Biology and Differentiation
1998-1999: Member of the Group of Istituto Superiore di Sanità for the Guidelines of Cellular and Genic Therapy
1996-: Member of the European Society for Dermatological Research


SEMINARS
Michele De Luca held over 130 seminars in several major Universities worldwide.

SCIENTIFIC MEETINGS
Michele De Luca has been invited speaker in more than 240 international meetings, congresses and workshops.

He was also one of the organizer of:
EMBO Conference “Cell therapy today: achievements, hopes and hypes”, September 9-13, 2015, Manchester, UK (Co-chairman)
ISSCR Regional Forum Series 2013, “Stem Cells in Translation”, Firenze, Italy, September 15-18, 2013 (Co-chairman)
Gordon Research Conferences, “Epithelial Differentiation and Keratinization”, II Ciocco, Lucca, Italy, May 29-June 3, 2005 (Chairman Issue Rising Session)
International workshop “Tissue Engineering and Cellular Cultures”, Villa Gualino, Torino, Italy, May 29-30, 2000 (Co-chairman)
First International Conference “Cutaneous Gene Therapy: Problems and Prospects”, NIH, Bethesda, MD, USA, March 23-24, 2000 (Co-chairman)
International workshop “Cultured Human Epidermis: Clinical Applications”, I.D.I. Istituto Dermopatico dell’Immacolata, Roma, Italy, October 10, 1997 (Chairman)
EMBO Workshop “Growth and Differentiation of Epithelial Cells”, Santa Margherita Ligure Genova, Italy, June 10-14, 1994 (Chairman)
Workshop “Adhesion and Extracellular Matrix”, Scuola Superiore di Oncologia e Scienze Biomediche, Santa Margherita Ligure, Genova, Italy, September 10-14, 1992 (Chairman).

BIBLIOGRAPHY
Author of over 140 publications in major international journals and book chapters.

PROJECTS
Michele De Luca has en extensive experience in translational research and has been involved in several project related to regenerative medicine (since 2006):
2024: Cellule staminali e medicina personalizzata: il caso dell'epidermolisi bollosa (HG7 3.0) funded by Regione Emilia-Romagna (CUP E97G22000680003)
2023: National Center for Gene Therapy and Drugs based on RNA Technology funded by PNRR (CUP E93C22001080001)
2023: "Learning From Animals How To Regenerate: multidisciplinary training programme in regenerative biology" (REGENERATE_IT) Funded by EU (EU Grant Agreement No.: 101073238)
2023: "A pilot in vitro and in vivo study for molecular characterization of epidermal stem cells and quality and safety assessment of epidermal cultures for combined cell and gene therapy" funded by MUR (PRIN CUP E53D23007310006)
2021: Custom-designed gene editing of induced epidermal stem cells for gene therapy of genetic diseases of squamous epithelia (Holo-GT), funded by European Commission (ERC Advanced Grant, 101019289)
2021: European consortium for communicating gene- and cell-based therapy information (EuroGCT Project)(H2020, 965241)
2021: “Allele-specific CRISPR- engineered Cpf1 genome editing to treat ocular surface disorder in ectrodactily-ectodermal dysplasia-clefting (EEC) syndrome” funded by Telethon (GGP20088)
2021: “L’epidermolisi bollosa (EB) a Modena dalla diagnosi alla terapia genica” funded by Debra Südtirol-Alto Adige 5×1000
2019: “Supercomputing Unified Platform Emilia-Romagna” (SUPER) funded by Regione Emilia-Romagna (CUP E81F18000330007)
2019: “Ottimizzazione degli approcci di terapia genica per l’Epidermolisi Bollosa” funded by da Debra Südtirol-Alto Adige 5x1000
2019: “Hologene7 2.0: L'Epidermolisi Bollosa (EB) a Modena dalla diagnosi alla terapia genica” funded by Regione Emilia-Romagna (POR-FESR-2014-2020 CUP E51F18000380009)
2018: “Hologene 7 come modello di sviluppo di una terapia avanzata a base di cellule staminali geneticamente corrette”, funded by da Debra Südtirol-Alto Adige 5x1000
2014: “Hologene 7 come modello di sviluppo di una terapia avanzata a base di cellule staminali geneticamente corrette” funded by Emilia-Romagna (POR-FESR-2014-2020 CUP E92I16000220005)
2014: “European Consortium for Communicating Stem Cell Research” – EUROSTEMCELL funded by European Union (H2020-Adhoc-2014-20 n. 652796)
2013: “Phase I/II ex vivo gene therapy clinical trial for recessive dystrophic epidermolysis bullosa using skin equivalent grafts genetically corrected with a COL7A1-encoding SIN retroviral vector – GENEGRAFT funded by European Union (FP7-HEALTH-2010 n. 261392)
2013: “Italian Regenerative Medicine Infrastructure (IRMI), a multiregional infrastructure for the development of advanced therapies aimed at organs and tissues regeneration” funded by M.I.U.R. (project n. CTN01_00177_888744)
2013: “La terapia genica per l’Epidermolisi Bollosa: dalla pre-clinica alla clinica” funded by Fondazione Cassa di Risparmio di Modena
2013: “Nuove strategie per la medicina rigenerativa” funded by M.I.U.R (PRIN 2010 n. 2010B5B2NL_002)
2010: “Centro di Medicina Rigenerativa - Tecnopolo di Modena” funded by Emilia-Romagna Region and European Union (Asse 1 POR FESR 2007-2013);
2008: “Pre-clinical development of gene therapy for epidermolysis bullosa” funded by Italian Ministry of Health (RF-EMR-2008-1210900)
2007: “Optimization of stem cell therapy for degenerative epithelial and muscle diseases” – OPTISTEM funded by European Union (FP7-HEALTH-2007 n. 223098)
2007: “Human epithelial stem cells: molecular characterization and development of clinical applications in regenerative medicine” funded by Emilia-Romagna Region (Progetto Regione-Università area 1b, medicina rigenerativa)
2006: “Gene therapy of junctional epidermolysis bullosa” funded by The French Muscular Dystrophy Association (CUP E91J10000420007)