Claudia Giachino
e-mail: claudia.giachino AT unito.it
affiliation: Università di Torino
research area(s): Genetics And Genomics, Stem Cells And Regenerative Medicine
Course:
Biomedical Sciences and Human Oncology
University/Istitution: Università di Torino
University/Istitution: Università di Torino
Claudia Giachino
Curriculum Vitae
Born in Zurich, Switzerland, on November 4th, 1964. Married, two children.
-Qualifications:
•1989 BSc (Hons) Biology, University of Turin, Italy.
•1995 PhD Human Genetics, University of Turin, Italy.
-Present position:
Associate Professor of Genetics, Department of Clinical and Biological Sciences, University of Turin, Italy.
-Training:
•1991 summer guest at Institut Pasteur, Paris, France, with Prof. T. Meo.
•1993-1994 fellow at the Basel Institute for Immunology, Basel, Switzerland, with Prof. A. Lanzavecchia.
•1995-1996 researcher at the Department of Medical Genetics, University of Turin, Italy, with Prof. N. Migone.
•1997 visiting scientist at the Basel Institute for Immunology, Basel, Switzerland.
•1998-2003 Head of the Experimental Immunology laboratory, IRCCS Maugeri Foundation, Pavia, Italy.
•1999 Assistant Professor of Molecular Biology, University of Turin, Italy.
•2006 Associate Professor of Genetics, University of Turin, Italy.
-Awards:
1996 has been awarded of the Roche Prize for Immunological Research.
-Major fields of interest:
• DNA damage and repair.
• Human mesenchymal stem cells: genetic stability and immunogenicity
• Induced pluripotent stem cells (iPS cells)
• Genomic instability syndromes
• T Cell Receptor transfer technology
• T cell responses in melanoma, vitiligo and related cutaneous diseases
-Guest Referee
Journals
• Blood
• Journal of Immunology
• Journal of Investigative Dermatology
• British Journal of Cancer
• Pigment Cell Research
• International Journal of Radiation Biology
• Journal of Autoimmune Diseases
Funding agencies
•Università degli Studi di Padova, Progetti di Ricerca per Giovani Ricercatori, since 2001
•The Wellcome Trust, London, UK, Scientific Grants Review, since 2005
•Cancer Research UK, London, UK, Scientific Grants Review, since 2005
-Teaching activity
•2001-2002 Bases of Biochemistry and Molecular Biology, Molecular Biology I module, Faculty of Medicine, University of Turin
•2003-2007 Biochemistry, Molecular Biology II module, Faculty of Medicine, University of Turin
•since 2009 Cellular and Genetic bases of Medicine, Human Genetics module, Faculty of Medicine, University of Turin
•2001-2002 Molecular Biology, Faculty of Medicine, TSLB, Cuneo
•since 2007 Human Genetics, Faculty of Medicine, TSLB, Cuneo
•since 2000 Molecular Biology, School of Specialization in Gastroenterology
•since 2003 Medical Genetics, School of Specialization in Infectious Diseases
•since 2003 Genetics of IG and TCR, School of Specialization in Medical Genetics
•since 2004 Genetics, School of Specialization in Hematology
Curriculum Vitae
Born in Zurich, Switzerland, on November 4th, 1964. Married, two children.
-Qualifications:
•1989 BSc (Hons) Biology, University of Turin, Italy.
•1995 PhD Human Genetics, University of Turin, Italy.
-Present position:
Associate Professor of Genetics, Department of Clinical and Biological Sciences, University of Turin, Italy.
-Training:
•1991 summer guest at Institut Pasteur, Paris, France, with Prof. T. Meo.
•1993-1994 fellow at the Basel Institute for Immunology, Basel, Switzerland, with Prof. A. Lanzavecchia.
•1995-1996 researcher at the Department of Medical Genetics, University of Turin, Italy, with Prof. N. Migone.
•1997 visiting scientist at the Basel Institute for Immunology, Basel, Switzerland.
•1998-2003 Head of the Experimental Immunology laboratory, IRCCS Maugeri Foundation, Pavia, Italy.
•1999 Assistant Professor of Molecular Biology, University of Turin, Italy.
•2006 Associate Professor of Genetics, University of Turin, Italy.
-Awards:
1996 has been awarded of the Roche Prize for Immunological Research.
-Major fields of interest:
• DNA damage and repair.
• Human mesenchymal stem cells: genetic stability and immunogenicity
• Induced pluripotent stem cells (iPS cells)
• Genomic instability syndromes
• T Cell Receptor transfer technology
• T cell responses in melanoma, vitiligo and related cutaneous diseases
-Guest Referee
Journals
• Blood
• Journal of Immunology
• Journal of Investigative Dermatology
• British Journal of Cancer
• Pigment Cell Research
• International Journal of Radiation Biology
• Journal of Autoimmune Diseases
Funding agencies
•Università degli Studi di Padova, Progetti di Ricerca per Giovani Ricercatori, since 2001
•The Wellcome Trust, London, UK, Scientific Grants Review, since 2005
•Cancer Research UK, London, UK, Scientific Grants Review, since 2005
-Teaching activity
•2001-2002 Bases of Biochemistry and Molecular Biology, Molecular Biology I module, Faculty of Medicine, University of Turin
•2003-2007 Biochemistry, Molecular Biology II module, Faculty of Medicine, University of Turin
•since 2009 Cellular and Genetic bases of Medicine, Human Genetics module, Faculty of Medicine, University of Turin
•2001-2002 Molecular Biology, Faculty of Medicine, TSLB, Cuneo
•since 2007 Human Genetics, Faculty of Medicine, TSLB, Cuneo
•since 2000 Molecular Biology, School of Specialization in Gastroenterology
•since 2003 Medical Genetics, School of Specialization in Infectious Diseases
•since 2003 Genetics of IG and TCR, School of Specialization in Medical Genetics
•since 2004 Genetics, School of Specialization in Hematology
Ongoing research projects
1) Human neural stem cells as an in vitro model to assess neurodegeneration caused by DNA damage response defects
Early progressive neurodegeneration is prominent feature of hereditary syndromes attributable to mutations in DNA damage response/repair (DDR) genes. Ataxia telangiectasia (A-T), A-T like disease (A-TLD) and Nijmegen breakage syndrome (NBS) are related neurodegenerative entities caused by mutations in ATM, MRE11 and NBS1 genes, respectively, whose encoded proteins function together in the DDR. Besides the accumulation of DNA damage as a mechanism for neurodegeneration, other factors including oxidative stress and oxidative DNA damage, mitochondrial dysfunction, unscheduled re-entry into cell cycle, have been variably implicated, at least in animal models. Whether similar mechanisms occur in human neural cells is unclear, due to the lack of appropriate model systems.
Taking advantage of normal human neural stem cells (hNSCs) possessing in vitro self-renewal and differentiation potential into neurons, astrocytes and oligodendrocytes, we aim to investigate the consequences of ATM, Nbs1 and Mre11 knockdown on neuronal cell fate, with a major focus on DNA damage mechanisms and interplay with intracellular oxidative stress, oxidative DNA damage and mitochondrial dysfunction.
2) The generation of induced pluripotent stem cells from adult mesenchymal stem cells and analysis of their genomic stability
We propose that the frequency of derivation of iPS cells may be greater if the cell being reprogrammed is an adult stem cell. Therefore, the overall aim of this project is to test the hypothesis that iPS cells can be generated with higher frequency from human adult mesenchymal stem cells (hMSCs) than from human dermal (skin) fibroblasts. Once iPS cells are established we will characterise their genomic stability and capacity for DNA repair. The specific scientific objectives are:
1. To compare the efficiency of derivation of iPS cells from adult human MSCs versus dermal fibroblasts.
2. To analyse the genomic stability and DNA damage responses in iPS cells generated from hMSCs.
3. To produce iPS cells from Ataxia Telangiectasia patients. This would represent a novel cellular model of the disease, suitable for studying both the neurodegenerative events and the other cellular phenotypes of AT patients.
3) Piattaforma ACTIVE – Advanced Cardiovascular Therapies
Il progetto ACTIVE è un progetto che mira a costituire una piattaforma tecnologica multidisciplinare orientata allo sviluppo di prodotti innovativi ad alto contenuto di ricerca industriale nell’ambito della “tecnologia biomedicale avanzata per la terapia cardiovascolare”.
Obiettivi scientifici e tecnologici
L’obiettivo scientifico e tecnologico è dunque duplice e mira allo sviluppo di:
1. Un nuovo stent a rilascio di farmaco multiplo combinato a supporto della terapia vascolare di angioplastica.
2. Una matrice di materiale bioartificiale bioinduttivo (Biomatrice) e relativo metodo di posizionamento (delivery system sia per intervento chirurgico tradizionale e MIS che percutaneo) allo scopo di guidare la formazione e rigenerazione di tessuto autologo nella parte infartuata del miocardio.
4) Bio-Nano-Tecnologie per la medicina rigenerativa: nanoparticelle fluorescenti funzionalizzate per l’imaging innovativo di cellule staminali mesenchimali umane
Il progetto è un approccio multidisciplinare orientato allo sviluppo di prodotti high-tech per imaging ad alto contenuto di ricerca applicata e trasferimento tecnologico.
Sono obiettivi del presente progetto:
1. la produzione di bio-nanomateriali innovativi per imaging molecolare in fluorescenza di cellule staminali, utili ad evidenziarne la crescita e il differenziamento in vitro e in vivo, che superino le limitazioni sopra riportate
2. la realizzazione prototipale di un microscopio a due fotoni dotato di OPO (optical parametric oscillator), in grado di visualizzare in 4D (3 dimensioni spaziali più temporale) cellule staminali marcate con questi bio-nanomateriali
3. la produzione di protocolli ottimizzati per l’imaging di cellule staminali mesenchimali umane, le cellule maggiormente utilizzate in medicina rigenerativa, utilizzando i prodotti sopra descritti.
1) Human neural stem cells as an in vitro model to assess neurodegeneration caused by DNA damage response defects
Early progressive neurodegeneration is prominent feature of hereditary syndromes attributable to mutations in DNA damage response/repair (DDR) genes. Ataxia telangiectasia (A-T), A-T like disease (A-TLD) and Nijmegen breakage syndrome (NBS) are related neurodegenerative entities caused by mutations in ATM, MRE11 and NBS1 genes, respectively, whose encoded proteins function together in the DDR. Besides the accumulation of DNA damage as a mechanism for neurodegeneration, other factors including oxidative stress and oxidative DNA damage, mitochondrial dysfunction, unscheduled re-entry into cell cycle, have been variably implicated, at least in animal models. Whether similar mechanisms occur in human neural cells is unclear, due to the lack of appropriate model systems.
Taking advantage of normal human neural stem cells (hNSCs) possessing in vitro self-renewal and differentiation potential into neurons, astrocytes and oligodendrocytes, we aim to investigate the consequences of ATM, Nbs1 and Mre11 knockdown on neuronal cell fate, with a major focus on DNA damage mechanisms and interplay with intracellular oxidative stress, oxidative DNA damage and mitochondrial dysfunction.
2) The generation of induced pluripotent stem cells from adult mesenchymal stem cells and analysis of their genomic stability
We propose that the frequency of derivation of iPS cells may be greater if the cell being reprogrammed is an adult stem cell. Therefore, the overall aim of this project is to test the hypothesis that iPS cells can be generated with higher frequency from human adult mesenchymal stem cells (hMSCs) than from human dermal (skin) fibroblasts. Once iPS cells are established we will characterise their genomic stability and capacity for DNA repair. The specific scientific objectives are:
1. To compare the efficiency of derivation of iPS cells from adult human MSCs versus dermal fibroblasts.
2. To analyse the genomic stability and DNA damage responses in iPS cells generated from hMSCs.
3. To produce iPS cells from Ataxia Telangiectasia patients. This would represent a novel cellular model of the disease, suitable for studying both the neurodegenerative events and the other cellular phenotypes of AT patients.
3) Piattaforma ACTIVE – Advanced Cardiovascular Therapies
Il progetto ACTIVE è un progetto che mira a costituire una piattaforma tecnologica multidisciplinare orientata allo sviluppo di prodotti innovativi ad alto contenuto di ricerca industriale nell’ambito della “tecnologia biomedicale avanzata per la terapia cardiovascolare”.
Obiettivi scientifici e tecnologici
L’obiettivo scientifico e tecnologico è dunque duplice e mira allo sviluppo di:
1. Un nuovo stent a rilascio di farmaco multiplo combinato a supporto della terapia vascolare di angioplastica.
2. Una matrice di materiale bioartificiale bioinduttivo (Biomatrice) e relativo metodo di posizionamento (delivery system sia per intervento chirurgico tradizionale e MIS che percutaneo) allo scopo di guidare la formazione e rigenerazione di tessuto autologo nella parte infartuata del miocardio.
4) Bio-Nano-Tecnologie per la medicina rigenerativa: nanoparticelle fluorescenti funzionalizzate per l’imaging innovativo di cellule staminali mesenchimali umane
Il progetto è un approccio multidisciplinare orientato allo sviluppo di prodotti high-tech per imaging ad alto contenuto di ricerca applicata e trasferimento tecnologico.
Sono obiettivi del presente progetto:
1. la produzione di bio-nanomateriali innovativi per imaging molecolare in fluorescenza di cellule staminali, utili ad evidenziarne la crescita e il differenziamento in vitro e in vivo, che superino le limitazioni sopra riportate
2. la realizzazione prototipale di un microscopio a due fotoni dotato di OPO (optical parametric oscillator), in grado di visualizzare in 4D (3 dimensioni spaziali più temporale) cellule staminali marcate con questi bio-nanomateriali
3. la produzione di protocolli ottimizzati per l’imaging di cellule staminali mesenchimali umane, le cellule maggiormente utilizzate in medicina rigenerativa, utilizzando i prodotti sopra descritti.
1. Lantelme E, Orlando L, Porcedda P, Turinetto V, De Marchi M, Amoroso A, Mantovani S, Giachino C. 2008. An in vitro model of T cell receptor revision in mature human CD8+ T cells. Molecular Immunol. 45:328-337.
2. C. Giachino. 2008. Capitolo di libro: Sistemi genetici complessi. In Biologia e Genetica di G. Del Sal, S. Ferrari e S. Bozzaro. A.Fantoni, M.Tripodi, Editore PICCIN.
3. Schallreuter KU, Bahadoran P, Picardo M, Slominski A, Elassiuty YE, Kemp EH, Giachino C, Liu JB, Luiten RM, Lambe T, Le Poole IC, Dammak I, Onay H, Zmijewski MA, Dell'Anna ML, Zeegers MP, Cornall RJ, Paus R, Ortonne JP, Westerhof W. 2008. Vitiligo pathogenesis: autoimmune disease, genetic defect, excessive reactive oxygen species, calcium imbalance, or what else? Exp Dermatol. 17:139-140.
4. Giachino C. 2008. Commentary 4. Exp Dermatol. 17:154-155.
5. Porcedda P, Turinetto V, Brusco A, Cavalieri S, Lantelme E, Orlando L, Ricardi U, Amoroso A, Gregori D, Giachino C. 2008. A rapid flow cytometry test based on histone H2AX phosphorylation for the sensitive and specific diagnosis of ataxia telangiectasia. Cytometry A. 73:508-16.
6. Porcedda P, Turinetto V, Orlando L, Lantelme E, Brusco A, De Marchi M, Amoroso A, Ricardi U, Gregori D, Giachino C. 2009. Two-tier analysis of histone H2AX phosphorylation allows the identification of Ataxia Telangiectasia heterozygotes. Radiotherapy and Oncology, 92:133-7.
7. Turinetto V, Porcedda P, Orlando L, De Marchi M, Amoroso A, Giachino C. 2009. The cyclin-dependent kinase inhibitor DRB induces nongenotoxic, DNA replication-independent apoptosis of normal and leukemic cells, regardless of their p53 status, BMC Cancer. 9:281-8
8. Circosta P, Granziero L, Follenzi A, Vigna E, Stella S, Vallario A, Elia AR, Gammaitoni L, Vitaggio K, Orso F, Geuna M, Sangiolo D, Todorovic M, Giachino C, Cignetti A. 2009. T cell receptor (TCR) gene transfer with lentiviral vectors allows efficient redirection of tumor specificity in naive and memory T cells without prior stimulation of endogenous TCR. Hum Gene Ther. 20:1576-88.
9. Zijno A, Porcedda P, Saini F, Allione A, Garofalo B, Marcon F, Guarrera S, Turinetto V, Minieri V, Funaro A, Crebelli R, Giachino C, Matullo G. 2010. Unsuitability of lymphoblastoid cell lines as surrogate of cryopreserved isolated lymphocytes for the analysis of DNA double-strand break repair activity. Mutat Res. 684:98-105.
10. Turinetto V, Porcedda P, Minieri V, Orlando L, Lantelme E, Accomasso L, Amoroso A, De Marchi M, Zannini L, Delia D, Giachino C. 2010. A novel defect in mitochondrial p53 accumulation following DNA damage confers apoptosis resistance in Ataxia Telangiectasia and Nijmegen Breakage Syndrome T-cells. DNA Repair. 9:1200-8.
11. Orlando L, Accomasso L, Circosta P, Turinetto V, Lantelme E, Porcedda P, Minieri V, Pautasso M, Willemsen RA, Gicnetti A, Giachino C. TCR transfer induces TCR-mediated tonic inhibition of RAG genes in human T cells. Mol. Immunol, in press.
2. C. Giachino. 2008. Capitolo di libro: Sistemi genetici complessi. In Biologia e Genetica di G. Del Sal, S. Ferrari e S. Bozzaro. A.Fantoni, M.Tripodi, Editore PICCIN.
3. Schallreuter KU, Bahadoran P, Picardo M, Slominski A, Elassiuty YE, Kemp EH, Giachino C, Liu JB, Luiten RM, Lambe T, Le Poole IC, Dammak I, Onay H, Zmijewski MA, Dell'Anna ML, Zeegers MP, Cornall RJ, Paus R, Ortonne JP, Westerhof W. 2008. Vitiligo pathogenesis: autoimmune disease, genetic defect, excessive reactive oxygen species, calcium imbalance, or what else? Exp Dermatol. 17:139-140.
4. Giachino C. 2008. Commentary 4. Exp Dermatol. 17:154-155.
5. Porcedda P, Turinetto V, Brusco A, Cavalieri S, Lantelme E, Orlando L, Ricardi U, Amoroso A, Gregori D, Giachino C. 2008. A rapid flow cytometry test based on histone H2AX phosphorylation for the sensitive and specific diagnosis of ataxia telangiectasia. Cytometry A. 73:508-16.
6. Porcedda P, Turinetto V, Orlando L, Lantelme E, Brusco A, De Marchi M, Amoroso A, Ricardi U, Gregori D, Giachino C. 2009. Two-tier analysis of histone H2AX phosphorylation allows the identification of Ataxia Telangiectasia heterozygotes. Radiotherapy and Oncology, 92:133-7.
7. Turinetto V, Porcedda P, Orlando L, De Marchi M, Amoroso A, Giachino C. 2009. The cyclin-dependent kinase inhibitor DRB induces nongenotoxic, DNA replication-independent apoptosis of normal and leukemic cells, regardless of their p53 status, BMC Cancer. 9:281-8
8. Circosta P, Granziero L, Follenzi A, Vigna E, Stella S, Vallario A, Elia AR, Gammaitoni L, Vitaggio K, Orso F, Geuna M, Sangiolo D, Todorovic M, Giachino C, Cignetti A. 2009. T cell receptor (TCR) gene transfer with lentiviral vectors allows efficient redirection of tumor specificity in naive and memory T cells without prior stimulation of endogenous TCR. Hum Gene Ther. 20:1576-88.
9. Zijno A, Porcedda P, Saini F, Allione A, Garofalo B, Marcon F, Guarrera S, Turinetto V, Minieri V, Funaro A, Crebelli R, Giachino C, Matullo G. 2010. Unsuitability of lymphoblastoid cell lines as surrogate of cryopreserved isolated lymphocytes for the analysis of DNA double-strand break repair activity. Mutat Res. 684:98-105.
10. Turinetto V, Porcedda P, Minieri V, Orlando L, Lantelme E, Accomasso L, Amoroso A, De Marchi M, Zannini L, Delia D, Giachino C. 2010. A novel defect in mitochondrial p53 accumulation following DNA damage confers apoptosis resistance in Ataxia Telangiectasia and Nijmegen Breakage Syndrome T-cells. DNA Repair. 9:1200-8.
11. Orlando L, Accomasso L, Circosta P, Turinetto V, Lantelme E, Porcedda P, Minieri V, Pautasso M, Willemsen RA, Gicnetti A, Giachino C. TCR transfer induces TCR-mediated tonic inhibition of RAG genes in human T cells. Mol. Immunol, in press.
No projects are available to students for the current accademic year.