Antonia Follenzi
e-mail: antonia.follenzi AT med.unipmn.it
affiliation: Università del Piemonte Orientale
research area(s): Stem Cells And Regenerative Medicine, Experimental Medicine
Course:
Biotechnologies For Human Health
University/Istitution: Università del Piemonte Orientale
University/Istitution: Università del Piemonte Orientale
1985: High School Diploma, Torino, Italy
1992: MD, University of Torino, Medical School(grade 110/110).
1997: Residency in Clinical Pathology, University of Torino (grade 70/70),
2001: PhD in Human Oncology, University of Torino, Medical School
1988-1992: Research Technician and Student, Department of Biomedical Science and Oncology, University of Torino Medical School (Prof. G. Gaudino)
1992-1995: Research Fellow, Department of Biomedical Sciences and Oncology, University of Torino Medical School (Prof. P.M. Comoglio)
1996-1997: Research Fellow, Department of Molecular Biology, Weizmann Institute of Science, Rehovot, Israel (Prof. Y. Yarden)
1997-1998: Research Fellow, Department of Biomedical Sciences and Oncology, University of Torino Medical School (Prof. P.M. Comoglio)
1998: Stage on Lentiviral Vectors technology at Cell Genesys (Foster City, CA) under the supervision of prof. Naldini from September to December (September-December).
1998-2003: Senior Research Fellow, Department of Oncological Sciences, Laboratory of Gene Transfer and Therapy; University of Torino Medical School (Prof. Luigi Naldini)
2003- 2011: Instructor and Visiting Assistant Professor, Marion Bessin Liver Research Center, Department of Pathology, Albert Einstein College of Medicine, Bronx, NY (Prof. Sanjeev Gupta)
2006-date: Assistant Professor of Histology, University of Piemonte Orientale, School of Medicine, Novara, Italy
1992: MD, University of Torino, Medical School(grade 110/110).
1997: Residency in Clinical Pathology, University of Torino (grade 70/70),
2001: PhD in Human Oncology, University of Torino, Medical School
1988-1992: Research Technician and Student, Department of Biomedical Science and Oncology, University of Torino Medical School (Prof. G. Gaudino)
1992-1995: Research Fellow, Department of Biomedical Sciences and Oncology, University of Torino Medical School (Prof. P.M. Comoglio)
1996-1997: Research Fellow, Department of Molecular Biology, Weizmann Institute of Science, Rehovot, Israel (Prof. Y. Yarden)
1997-1998: Research Fellow, Department of Biomedical Sciences and Oncology, University of Torino Medical School (Prof. P.M. Comoglio)
1998: Stage on Lentiviral Vectors technology at Cell Genesys (Foster City, CA) under the supervision of prof. Naldini from September to December (September-December).
1998-2003: Senior Research Fellow, Department of Oncological Sciences, Laboratory of Gene Transfer and Therapy; University of Torino Medical School (Prof. Luigi Naldini)
2003- 2011: Instructor and Visiting Assistant Professor, Marion Bessin Liver Research Center, Department of Pathology, Albert Einstein College of Medicine, Bronx, NY (Prof. Sanjeev Gupta)
2006-date: Assistant Professor of Histology, University of Piemonte Orientale, School of Medicine, Novara, Italy
- Gene transfer by Lentiviral vectors
- Liver cell transplantation
- Cell and Gene Therapy of Hemophilia
AWARDS AND HONORS:
1989-1990: Research Fellowship, "Comitato Regionale Piemontese Gigi Ghirotti"
1996: Research Fellowship, "FIRC" (Italian Federation for Cancer Research) at Weizmann Institute of Science - Rehovot (Israel)
2000: Research Fellowship, ISS (Italian Health Ministry) for AIDS Research Program
2000 American Society for Gene Therapy Travel Grant Award
2000: Outstanding Research Award for Students and Fellows, American Society for Gene Therapy, Denver
2005: Liver Scholar Award from the American Liver Foundation/AASLD
2005: Career Development Award from the National Hemophilia Foundation (declined in favor of ALF award)
2008: Young Investigator Award from European Society of Gene and Cell Therapy
2010: CSL-Behring Prof. Heimburger Award
Reviewer for International Journal
Human Gene Therapy, Journal of Gene Medicine, Stem Cells, Journal of Clinical Investigation, Experimental Cell Research, Liver International, Blood
- Liver cell transplantation
- Cell and Gene Therapy of Hemophilia
AWARDS AND HONORS:
1989-1990: Research Fellowship, "Comitato Regionale Piemontese Gigi Ghirotti"
1996: Research Fellowship, "FIRC" (Italian Federation for Cancer Research) at Weizmann Institute of Science - Rehovot (Israel)
2000: Research Fellowship, ISS (Italian Health Ministry) for AIDS Research Program
2000 American Society for Gene Therapy Travel Grant Award
2000: Outstanding Research Award for Students and Fellows, American Society for Gene Therapy, Denver
2005: Liver Scholar Award from the American Liver Foundation/AASLD
2005: Career Development Award from the National Hemophilia Foundation (declined in favor of ALF award)
2008: Young Investigator Award from European Society of Gene and Cell Therapy
2010: CSL-Behring Prof. Heimburger Award
Reviewer for International Journal
Human Gene Therapy, Journal of Gene Medicine, Stem Cells, Journal of Clinical Investigation, Experimental Cell Research, Liver International, Blood
1. Martinez-Vicente M, Talloczy Z, Kaushik S, Massey AC, Mazzulli J, Mosharov EV, Hodara R, Fredenburg R, Wu DC, Follenzi A, Dauer W, Przedborski S, Ischiropoulos H, Lansbury PT, Sulzer D, Cuervo AM. Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy. J Clin Invest.118:777-88 (2008)
2. Joseph A, Zheng J H, Follenzi A, DiLorenzo T, Sango K, Hyman J, Chen K, Trocha A, Brander C, Hooijberg E, Vignali DA., Walker BD and Goldstein H. Genetic Engineering of HIV-specific Cytotoxic T Lymphocytes that Potently Inhibit In Vivo HIV-1 Infection by the Transduction of Peripheral Blood CD8 T Lymphocytes with Lentiviral Vectors Encoding HIV-specific TCR Genes Derived From an HIV-1-Specific CTL Clone. J Virology, 82:3078-89 (2008)
3. Massey AC., Follenzi A, Kiffin R, Zhang C and Cuervo AM. Early cellular changes after blockage of chaperone-mediated autophagy. Autophagy, 4:442-56 (2008)
4. Follenzi A., Benten D., Novikoff F., Faulkner L., Raut S., Gupta S. Transplanted Endothelial Cells Repopulate the Liver Endothelium and Correct the Phenotype of Hemophilia A Mice. J Clin Invest. 118:935-945 (2008)
5. Inada M., Follenzi A, Surana M, Cheng K., Benten D., Qian H and Gupta S. Fetal human liver epithelial cells undergo meso-epithelial phenotype reversion with reprogramming of cytokine signaling. J Cell Sci. 121:1002-13. (2008)
6. Kojaoghlanian T., Joseph A., Follenzi A., Zheng JH., Leiser M., Fleisher N., Horwitz MS., Di Lorenzo TP., and Goldstein H. Lentivectors encoding immunosuppressive proteins genetically engineer pancreatic beta-cells to correct diabetes in allogeneic mice. Gene Therapy 16(3):340-8 (2009) Epub 2008 Dec 25.
7. Merlin S, Pietronave S, Locarno D, Valente G, Follenzi A and Prat M. Deletion of the ectodomain unleashes the transforming, invasive, and tumorigenic potential of the MET oncogene. Cancer Sci. 100(4):633-8 (2009)
8. Miyawaki T, Ofengeim D, Noh KM, Latuszek-Barrantes A, Hemmings BA, Follenzi A, Zukin RS. The endogenous inhibitor of Akt, CTMP, is critical to ischemia-induced neuronal death. Nat Neurosci. 12(5):618-26 (2009)
9. Krohn N, Kapoor N, Enami Y, Follenzi Y, Bandi S, Joseph B and Gupta S Hepatocyte Transplantation-Induced Liver Inflammation Is Driven by Cytokines-Chemokines Associated With Neutrophils and Kupffer Cells. Gastroenterology 136(5): 1806-1817 (2009)
10. Salvucci O, Maric D, Economopoulu M, Merlin S, Follenzi S, and Tosato G. Ephrin B reverse signaling contributes to endothelial and mural cell assembly into vascular structures. Blood,114(8):1707-16 (2009)
11. 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. TCR gene transfer with lentiviral vectors allows efficient redirection of tumor specificity in naïve and memory T-cells without prior stimulation of endogenous TCR. Hum Gene Ther. 20(12):1576-88 (2009)
12. Cheng K, Follenzi A, Surana M, Fleischer N, Gupta S.Switching of mesodermal and endodermal properties in hTERT-modified and expanded fetal human pancreatic progenitor cells. Stem Cell Res Ther. 15;1:6 (2010)
13. Joseph A, Zheng JH, Chen K, Dutta M, Chen C, Stiegler G, Kunert R, Follenzi A, Goldstein H. Inhibition of in vivo HIV infection in humanized mice by gene therapy of human hematopoietic stem cells with a lentiviral vector encoding a broadly neutralizing anti-HIV antibody. J Virol. 84:6645-53 (2010)
14. Maitra R, Follenzi A, Yaghoobian A, Montagna C, Merlin S, Cannizzo ES, Hardin JA, Cobelli N, Stanley ER, Santambrogio L.Dendritic cell-mediated in vivo bone resorption. J Immunol. 185(3):1485-91 (2010)
15. Gardenghi S, Ramos P, Marongiu MF, Melchiori L, Breda L, Guy E, Muirhead K, Rao N, Roy CN, Andrews NC, Nemeth E, Follenzi A, An X, Mohandas N, Ginzburg Y, Rachmilewitz EA, Giardina PJ, Grady RW and Rivella S. Hepcidin as a therapeutic tool to limit iron overload and improve anemia in beta-thalassemic mice. J Clin Invest. 120:4466-77 (2010)
16. Ramos P, Guy E, Chen N, Proenca CC, Gardenghi S, Casu C, Follenzi A, Van Rooijen N, Grady RW, de Sousa M, Rivella S.Enhanced erythropoiesis in Hfe-KO mice indicates a role for Hfe in the modulation of erythroid iron homeostasis. Blood.117:1379-89 (2011)
17. Sahu R, Kaushik S, Clement CC, Cannizzo ES, Scharf B, Follenzi A, Potolicchio I, Nieves E, Cuervo AM, Santambrogio L. Microautophagy of cytosolic proteins by late endosomes. Dev Cell. 20:131-9 (2011)
18. Dal Ponte C, Alchera E, Follenzi A, Imarisio C, Prat M, Albano E, Carini R. Pharmacological postconditioning protects against hepatic ischemia/reperfusion injury. Liver Transpl. 17:474-82 (2011).
2. Joseph A, Zheng J H, Follenzi A, DiLorenzo T, Sango K, Hyman J, Chen K, Trocha A, Brander C, Hooijberg E, Vignali DA., Walker BD and Goldstein H. Genetic Engineering of HIV-specific Cytotoxic T Lymphocytes that Potently Inhibit In Vivo HIV-1 Infection by the Transduction of Peripheral Blood CD8 T Lymphocytes with Lentiviral Vectors Encoding HIV-specific TCR Genes Derived From an HIV-1-Specific CTL Clone. J Virology, 82:3078-89 (2008)
3. Massey AC., Follenzi A, Kiffin R, Zhang C and Cuervo AM. Early cellular changes after blockage of chaperone-mediated autophagy. Autophagy, 4:442-56 (2008)
4. Follenzi A., Benten D., Novikoff F., Faulkner L., Raut S., Gupta S. Transplanted Endothelial Cells Repopulate the Liver Endothelium and Correct the Phenotype of Hemophilia A Mice. J Clin Invest. 118:935-945 (2008)
5. Inada M., Follenzi A, Surana M, Cheng K., Benten D., Qian H and Gupta S. Fetal human liver epithelial cells undergo meso-epithelial phenotype reversion with reprogramming of cytokine signaling. J Cell Sci. 121:1002-13. (2008)
6. Kojaoghlanian T., Joseph A., Follenzi A., Zheng JH., Leiser M., Fleisher N., Horwitz MS., Di Lorenzo TP., and Goldstein H. Lentivectors encoding immunosuppressive proteins genetically engineer pancreatic beta-cells to correct diabetes in allogeneic mice. Gene Therapy 16(3):340-8 (2009) Epub 2008 Dec 25.
7. Merlin S, Pietronave S, Locarno D, Valente G, Follenzi A and Prat M. Deletion of the ectodomain unleashes the transforming, invasive, and tumorigenic potential of the MET oncogene. Cancer Sci. 100(4):633-8 (2009)
8. Miyawaki T, Ofengeim D, Noh KM, Latuszek-Barrantes A, Hemmings BA, Follenzi A, Zukin RS. The endogenous inhibitor of Akt, CTMP, is critical to ischemia-induced neuronal death. Nat Neurosci. 12(5):618-26 (2009)
9. Krohn N, Kapoor N, Enami Y, Follenzi Y, Bandi S, Joseph B and Gupta S Hepatocyte Transplantation-Induced Liver Inflammation Is Driven by Cytokines-Chemokines Associated With Neutrophils and Kupffer Cells. Gastroenterology 136(5): 1806-1817 (2009)
10. Salvucci O, Maric D, Economopoulu M, Merlin S, Follenzi S, and Tosato G. Ephrin B reverse signaling contributes to endothelial and mural cell assembly into vascular structures. Blood,114(8):1707-16 (2009)
11. 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. TCR gene transfer with lentiviral vectors allows efficient redirection of tumor specificity in naïve and memory T-cells without prior stimulation of endogenous TCR. Hum Gene Ther. 20(12):1576-88 (2009)
12. Cheng K, Follenzi A, Surana M, Fleischer N, Gupta S.Switching of mesodermal and endodermal properties in hTERT-modified and expanded fetal human pancreatic progenitor cells. Stem Cell Res Ther. 15;1:6 (2010)
13. Joseph A, Zheng JH, Chen K, Dutta M, Chen C, Stiegler G, Kunert R, Follenzi A, Goldstein H. Inhibition of in vivo HIV infection in humanized mice by gene therapy of human hematopoietic stem cells with a lentiviral vector encoding a broadly neutralizing anti-HIV antibody. J Virol. 84:6645-53 (2010)
14. Maitra R, Follenzi A, Yaghoobian A, Montagna C, Merlin S, Cannizzo ES, Hardin JA, Cobelli N, Stanley ER, Santambrogio L.Dendritic cell-mediated in vivo bone resorption. J Immunol. 185(3):1485-91 (2010)
15. Gardenghi S, Ramos P, Marongiu MF, Melchiori L, Breda L, Guy E, Muirhead K, Rao N, Roy CN, Andrews NC, Nemeth E, Follenzi A, An X, Mohandas N, Ginzburg Y, Rachmilewitz EA, Giardina PJ, Grady RW and Rivella S. Hepcidin as a therapeutic tool to limit iron overload and improve anemia in beta-thalassemic mice. J Clin Invest. 120:4466-77 (2010)
16. Ramos P, Guy E, Chen N, Proenca CC, Gardenghi S, Casu C, Follenzi A, Van Rooijen N, Grady RW, de Sousa M, Rivella S.Enhanced erythropoiesis in Hfe-KO mice indicates a role for Hfe in the modulation of erythroid iron homeostasis. Blood.117:1379-89 (2011)
17. Sahu R, Kaushik S, Clement CC, Cannizzo ES, Scharf B, Follenzi A, Potolicchio I, Nieves E, Cuervo AM, Santambrogio L. Microautophagy of cytosolic proteins by late endosomes. Dev Cell. 20:131-9 (2011)
18. Dal Ponte C, Alchera E, Follenzi A, Imarisio C, Prat M, Albano E, Carini R. Pharmacological postconditioning protects against hepatic ischemia/reperfusion injury. Liver Transpl. 17:474-82 (2011).
Project Title:
Cell and gene therapy of Hemophilia A
New approaches to cure hemophilia A require insights into cell compartments capable of producing FVIII. Recently, I demonstrated that liver sinusoidal endothelial cells (LSEC) and hematopoietic-derived cells also produce and secrete FVIII. Indeed, we were able to correct the bleeding phenotype of hemophilia A mice by infusion of normal LSEC. We have also found that these mice can be treated by reconstitution with wild-type BM, indicating that BM-derived cells, of hematopoietic, mesenchymal or even endothelial origin, can produce and secrete FVIII. Based on these findings in mice, we propose that human LSEC, cord blood and bone marrow cells and iPS-patient derived after LV correction may be suitable sources of FVIII to be used for cell replacement therapy as a treatment for hemophilia A. The results of the proposed studies not only will increase our knowledge of the biological activity of these cells, but may also impact on the future course of hemophilia A therapy by enlightening novel and yet unrecognized therapeutic targets and by providing proof-of-feasibility of a new cell-gene therapy strategy.
The Specific Aims of the project are the following:
Aim 1. To investigate the engraftment potential and FVIII-producing capacity of human LSEC.
Aim 2. A) To determine which human CB- and BM-derived cells are capable of producing and secreting FVIII and B) To determine whether replacement of BM in sublethally-irradiated gamma-null NOD/SCID Hemophilia A mice with human BM or CB derived cells will successfully repopulate mesenchymal and monocyte compartments with appropriate functions and correct their bleeding phenotype.
Aim 3. To demonstrate the feasibility to genetically modify the human cells (LSEC, BM and CB derived cells) by lentiviral vectors.
Aim 4. Generation and characterization of Hemophilia A-specific iPS cells
The Specific Aims of the project are the following:
Aim 1. To investigate the engraftment potential and FVIII-producing capacity of human LSEC.
Aim 2. A) To determine which human CB- and BM-derived cells are capable of producing and secreting FVIII and B) To determine whether replacement of BM in sublethally-irradiated gamma-null NOD/SCID Hemophilia A mice with human BM or CB derived cells will successfully repopulate mesenchymal and monocyte compartments with appropriate functions and correct their bleeding phenotype.
Aim 3. To demonstrate the feasibility to genetically modify the human cells (LSEC, BM and CB derived cells) by lentiviral vectors.
Aim 4. Generation and characterization of Hemophilia A-specific iPS cells