BIOGRAPHICAL SKETCH NAME: Jan A. Nolta, Ph.D. eRA COMMONS USER NAME: POSITION TITLE: Jnolta Professor, Director of the Stem Cell Program, University of California, Davis EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION California State University Sacramento, CA University of Southern California, L.A., CA Childrens Hospital of Los Angeles, CA DEGREE B.S.B.S. Ph.D. Ph.D. Post-Doc Postdoc YEAR(s) 1984 1984 1984 1990-94 1994 1994-97 1996 FIELD OF STUDY Biology Biology Biology Molecular Microbiology Microbiology Stem Gene Post-Doc Cell Therapy Gene 1996 Therapy Personal Statement: I am the Director of the Stem Cell Program at UC Davis School of Medicine, and I direct the Institute for Regenerative > Cures. The UC Davis stem cell program has over 150 faculty members collaborating to work toward stem cell-related cures for a spectrum of diseases and injuries. The current research in our laboratory is focused on developing therapies that will use stem cells to deliver factors for treating disease and tissue injury. Our group focuses on “bench to the bedside” research, and I have been involved in numerous clinical trials of gene and cell therapy. I have more than 25 years’ experience with human stem cells, have published over 100 manuscripts in the stem cell field and have authored 30 book chapters. I have served on over 200 review panels for the National Institutes of Health and other grant-funding agencies, am Editor for the Journal “Stem Cells” and editor of the Book "Genetic Engineering of Mesenchymal Stem Cells". In 2012 I received a prestigious Transformative Grant Award from the NIH office of the Director, based on our novel work on cell-to-cell communication. My passion is to help our teams bring exciting advances in stem cell therapy from the bench to the bedside, to develop novel clinical trials of regenerative medicine to help our patients who have few other options. Professional Experience and Duties: Professor, Director of the Stem Cell Program and Institute for Regenerative Cures, Scientific Director-GMP Facility for Cell and Gene Therapy, UC Davis School of Medicine, Department of Internal Medicine, Division of Hematology/ Oncology. November 1, 2006 - present. Associate Professor of Medicine & Pathology/Immunology, Washington University School of Medicine, Div. Oncology, - Stem Cell Program (May 2002 –December 2006). Tenure granted September 2002. Scientific Director, Washington University Good Manufacturing Practice (GMP) Facility (December 2002 to Feb 07). Washington Univ. Animal Studies Committee (2003- 2006) Member, CHLA Animal Care Committee (1997 – 2002) Assistant Professor of Pediatrics, Univ. of Southern California School of Medicine, L.A., CA (June 1997- May 2002) Member, Norris Comprehensive Cancer Center, Developmental Therapeutics & Clin. Trials Research program (1998-02) Chair, Institutional Biosafety Committee, Childrens Hospital of Los Angeles (May 2000 – May 2002) Graduate Faculty, USC School of Medicine, Department of Developmental Biology (July 1997-March 2002) Postdoctoral Fellow, John Connell Gene Therapy Foundation –Donald Kohn’s laboratory, CHLA (1994-1997) Graduate Student, University of Southern California School of Medicine, Dept. of Molecular Microbiology (1990 – 1994) Research Specialist II-IV, Dept. Research Immunology/ BMT, Childrens Hospital Los Angeles, L.A., CA (1987-1990) Hematology Laboratory Technician/ Night Shift Supervisor, UC Davis Medical Center (1983-87) Honors: Honors at Entrance, California State University; Dean's Honor List, CSUS, UC Davis, USC Lifetime Member California Scholarship Foundation (1980), BA Scholarship (‘83), Golden Key Honor Society (‘84) American Society of Hematology Travel Grants (1988-1995), NRSA Training Grant (1991 - 1993) Dean's Honor List, USC Graduate School (4.0 GPA; 1990 - 1994) International Society of Hematology New Investigator Award (1996) Research Career and Development Award, CHLA Research Institute (1996) James Shannon Directors Award, NIH NIDDK (1997) Huntington’s Disease Society of America Distinguished Leadership Award (2008) California State University, Sacramento Distinguished Service Award (2009) Deans Award for Team Excellence (2011), Deans Award for Excellence in Mentoring (2013) Elected: AAAS Fellow (2013) Top 50 most influential global stem cell scientists (2013) Activities: Member: American Society of Hematology, AAAS, International Society of Experimental Hematology; American Society for Gene Therapy, International Society for Stem Cell Research (ISSCR) Gene T International Society for Hematology and Graft Engineering (ISHAGE) Gene Therapy Committee (1998-99) Moderator/ reviewer/session chair at the Annual Meeting of the American Society for Hematology (1997 – 2009) P01 review panels & site visits, NHLBI, NCI, NIDDK 1999-2007, Chair NIDDK, NHLBI stem cell reviews 2003, Reviewer, Italian Telethon Grants Administration Program, 1998 – present, NIH NCRR COBRE grants 2008 US Army BCA grant review sessions, 2000, 2001.Chair: IBC Gene Therapy Workshop, Lake Tahoe, CA, 1999 External Advisory Boards: Univ. Minnesota Stem Cell PPG (2000-2002) & Seattle CF Gene Therapy Program, 2000 Ad-hoc member, HEM-1 and HEM-2 Study Sections, NIH (1998- 2003) International Society of Experimental Hematology (ISEH) Nominating Committee, 2001-4. Chair: 2003-4. American Society of Gene and Cell Therapy, Hematopoietic Therapy committee, 2003-2006. Chair, 2004-2006, Chair, ASGT embryonic stem cell and tissue engineering committee, 2006-2009, nominating committee 2009-. Editorial Board, Human Gene Therapy, 2001-2009, Editorial Board, Experimental Hematology, 2000 – present Section Editor, Leukemia: stem cells, 2001 – 2002, Gene Therapy 2000-2006. Editorial Board,1999-2005. Editorial Board, Blood, September 2002 – 2008, Editorial Board, Molecular Therapy, 2003- 2006. Full Member, Hematology B Study Section, National Institutes of Health, May 2003-June 2007. Ad Hoc 2008Chair, New York Stem Cell Research Program (NYSTEM) Major Shared Facilities Panel, 2008 - 2010 Member, Huntington’s disease Communications Group of the Huntington’s Study group, 2008-present Member, International Society of Cell Therapy Commercialization Committee, 2011-present NHLBI Production Assistance for Cellular Therapies (PACT) External Expert Panel Member, 2010-present Associate Editor, Stem Cells, February 2008 – December 2011 Editor, Stem Cells, January 2012 - 2016 Publications (Selected, of over 100 peer-reviewed manuscripts) 1. Nolta JA, Kohn DB. Expression of human Glucocerebrosidase in murine Long Term Bone Marrow Cultures after retroviral vector-mediated transfer. Blood 75:787-97, 1990. 2. Ozkaynak M, Nolta JA, Parkman R. Purging of rhabdomyosarcoma cells using 4-HC. Cancer Research 50:145558,1990. 3. Nolta JA, Kohn DB. Comparison of the effects of growth factors on retroviral vector-mediated gene transfer and the proliferative status of human hematopoietic progenitor cells. Human Gene Therapy 1(3):257-268, 1990. 4. Lenarsky C, Weinberg K, Nolta J, Annett G, Kohn D, Parkman R. Autologous bone marrow transplantation with 4HC purged marrows for children with acute non-lymphoblastic leukemia in 2nd remission. Bone Marrow Transplantation 6:425-429, 1990. 5. Weinthal J, Nolta JA, Yu X-J, Lilley J, Uribe L, Kohn D. Expression of human GC following retroviral vectormediated transduction of murine hematopoietic stem cells. Bone Marrow Transplantation 8:403-412, 1991. 6. Kohn D, Nolta J, Yu X-J, Lilley J, Crooks G. Towards gene therapy for Gaucher disease. Human Gene Therapy 2:101-105, 1991. 7. Tishler DM, Weinberg KI, Sender LS, Nolta JA, Raffel C. Multidrug resistance gene expression in pediatric primitive neuroectodermal tumors of the central nervous system. Journal of Neurosurgery 76:507-512, 1992. 8. Nolta JA, Crooks GM, Overell RW, and Kohn DB. Retroviral vector-mediated gene transfer into primitive human hematopoietic progenitor cells: effects of mast cell growth factor (MGF) combined with other cytokines. Expt. Hematology 20:1065-1071, 1992. 9. Nolta JA, Yu XJ, Kohn DB. Retroviral-mediated transfer of the huGC gene into Gaucher BM. J. Clin. Invest. 90:342-348, 1992. 10. Nolta JA, Hanley M, Kohn DB. Sustained human hematopoiesis in immunodeficient mice by co-transplantation of marrow stroma expressing human IL-3: Analysis of gene transduction of long-lived progenitors. Blood 83:30413051, 1994. 11. Nolta JA, Smogorzewska EM, Kohn DB. Analysis of optimal conditions for retroviral-mediated transduction of primitive human hematopoietic stem cells. Blood 86; 101 - 110, 1994. 12. Hanley ME, Nolta JA, Parkman R, and Kohn DB. Umbilical cord blood cell transduction by retroviral vectors: preclinical studies to optimize gene transfer. Blood Cells 20; 539 - 546, 1994. 13. Wells S, Kohn D, Nolta JA. Stromal support optimizes transduction of Gaucher LTCIC. Gene Therapy 2, 512-520, 1994. 14. Kohn DB, Weinberg KI, Nolta JA., Parkman R. et al. Engraftment of gene-modified cells from Umbilical Cord Blood in neonates with ADA deficiency. Nature Medicine 1; 1017-1023, 1995. 15. Nolta JA, Dao MA, and Kohn DB. Transduction of pluripotent human hematopoietic stem cells demonstrated by clonal analysis after engraftment in immune deficient mice. Proc. Natl. Acad. Sci. USA 93; 2414-2419, 1996. 16. Dao MA and Nolta JA. Inclusion of IL-3 During Retroviral-Mediated Transduction on Stromal Support Does Not Increase the Extent of Gene Transfer Into Long-Term Engrafting Human stem cells. Cell. Mol. Ther. 3:8190, 1997. 17. Dao MA, Hannum CH, and Nolta JA. FLT3 ligand preserves the ability of human CD34+ progenitors to sustain 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. long-term hematopoiesis in immune deficient mice following ex-vivo retroviral - mediated transduction. Blood 89:446-456, 1997. Nolta JA, Kohn DB. Hematopoietic stem cells for gene therapy. In Stem Cells, Ed: C. Potten, Academic Press, pp. 447-61, 1997. Dao MA, Yu XJ, and Nolta JA. Clonal diversity of retroviral vector - marked primitive human hematopoietic progenitors recovered from long-term engrafted immune deficient mice. Expt. Hematol. 25:1357-1366, 1997. Dao MA, Pepper, KA, and Nolta JA. Human cytokine production from engineered stromal cells influences hematopoietic development from co-transplanted human CD34+ progenitors in immune deficient mice. Stem Cells 15:443-453, 1997. Dao MA, Hashino K, Kato I, and Nolta JA. Adhesion to fibronectin maintains regenerative capacity during ex-vivo culture and transduction of human hematopoietic stem and progenitor cells. Blood 92: 4612-4621, 1998. Dao M, Nolta JA. Hematopoietic stem cells as targets for Gene Therapy: Cancer Research, Therapy and Control 7:19-25, 1998. Dunbar CE, Kohn DB, Schiffmann R, Barton NW, Nolta JA, Esplin J, Pensiero M, Emmons RVB, Leitman S, Krebs CB, Carter CC, Brady RO, and Karlsson S. Retroviral transfer of the glucocerebrosidase gene into CD34+ cells from patients with Gaucher disease: in vivo detection of transduced cells without myeloablation. Human Gene Therapy 9: 2692-2640, 1998. Dao MA, Shah AJ, Smogorzewska EM, Crooks GC, and Nolta JA. Comparison of human hematopoietic progenitor content and retroviral marking in immune deficient mice transplanted with CD34+ vs. CD34+/38- cells. Blood 91(3): 1243-1255, 1998. Kohn DB, Hershfeld MS, Nolta JA, Parkman R et al. Selective accumulation of T cells containing a normal ADA gene four years after transduced autologous UCB CD34+ cell BMT in ADA-deficient SCID neonates. Nature Medicine 4:775-780, 1998. Dao M, Taylor N, Nolta J. Reduction in levels of the CDK inhibitor p27kip-1 coupled with TGF neutralization induces cell cycle entry & increases retroviral transduction of primitive human hematopoietic cells. Proc Natl Acad Sci USA 95:13006-13011, 1998. Epstein A, Liu M, Nolta JA, and Durden DL. Cbl functions downstream of SRC kinases in FcRI signaling in primary human macrophages. Journal of Leukocyte Biology, 65: 1-12, 1999. Dao MA and Nolta JA. Molecular control of cell cycle progression in primary human hematopoietic stem cells: Methods to increase levels of retroviral - mediated transduction. Leukemia 13:1473-1480, 1999. Arakawa-Hoyt J, MA Dao, F Thiemann, KI Weinberg, GM Crooks, and Nolta JA. The number and generative capacity of human B cell progenitors is higher in umbilical cord blood than in bone marrow. Bone Marrow Transplantation 24: 1167-1176, 1999. Dao MA, Tsark E, Nolta JA. Animal xenograft models for evaluation of gene transfer into human hematopoietic stem cells. Current Opinion in Molecular Therapeutics 1:553-557, 1999. Parkman R, Weinberg K, Crooks G, Nolta J, Kohn D. Gene therapy for ADA deficiency. Ann. Rev. Med. 51:33-47, 2000. Evans M, Jordan C, Nolta, JA, Wivel N et al. Clinical Infection Control in Gene Therapy. Infection Control 21: 659 – 673, 2000. Tsark E, Dao MA, Weinberg KI, and Nolta JA. Interleukin 7 (IL-7) enhances the responsiveness of human T cells that develop in the bone marrow of athymic mice. Journal of Immunology 166: 170 – 181, 2001. Wang X, Dao MA, Kuo I and Nolta JA. Phenotypic comparison of extrathymic human bone marrow-derived T cells with thymic-selected T cells recovered from different tissues. Clinical Immunology, 100 (3), 339 - 348, 2001. Nolta JA, Thiemann F, Arakawa J, Dao M, Barsky, Moore KA, Lemischka I, Crooks GM. The AFT024 stromal cell line supports long-term ex vivo maintenance of engrafting multipotent human hematopoietic progenitors. Leukemia 16: 352-361, 2002. Nolta JA. Cell - Based Therapy: will it replace pharmaceuticals in some cases? Current Drugs 4:212-218, 2002 Dao MA., Hwa J and Nolta JA. Molecular mechanism of transforming growth factor beta-mediated cell-cycle modulation in primary human CD34(+) progenitors. Blood. Jan 15; 99 (2):499-506, 2002. Gussoni E, Meyerrose TE, Nolta JA, Weinberg KA, Kunkel LM, et al. Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. Journal of Clinical Investigation Sept.; 110(6):807-14, 2002. Dao MA, Arevalo JA, and Nolta JA. Reversibility of CD34 expression on human hematopoietic stem cells that retain the capacity for secondary reconstitution. Blood Jan 1; 101(1); 112-118, 2003. Wu G, Nolta JA, Starnes V, and Cramer D. Migration of mesenchymal stem cells to heart allografts during chronic rejection. Transplantation Mar 15; 75(5): 679-685, 2003. 41. Bauer G, Nolta JA, Walker JE, Devine S, DiPersio J. Design and construction of a GMP facility for cellular and gene 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. therapy in an academic center-implementing new regulatory requirements. Stem Cell and Cellular Therapy 1:54-61, 2003. Schmidt M, Carbonaro D, Speckmann C, Bohnsack J, Nolta JA, Kohn D, von Kalle C. Clonality Analysis after retroviral–mediated gene transfer to cord blood CD34+ cells of an ADA-deficient SCID infant. Nature Medicine, Apr1; 9(4); 463-68, 2003. Wang X, Ge S, McNamara G, Hao QL, Crooks GM, and Nolta JA. Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice transplanted with highly purified human stem cells. Blood, May 15; 101 (10): 4201-4208, 2003. Kohn DB, Dunbar C, Bodine D, Kiem HP, Candotti F, Tisdale J, Blau CA, Sorrentino B, Nolta J, et al. American Society of Gene Therapy ad hoc subcommittee on retroviral-mediated gene transfer to stem cells. Mol Ther. Aug;8(2):180-7, 2003 Mohamedali A, Moreau-Gaudry F, Richard E, Xia P, Nolta J, Malik P. Self-inactivating lentiviral vectors resist proviral methylation but do not confer position-independent expression in hematopoietic stem cells. Mol Ther. Aug;10(2):249-59, 2004. J Bonde, D Hess, J Nolta. Recent advances in hematopoietic stem cell biology. Curr Opin Hematol. Nov;11(6):3928, 2004. D Hess, T Meyerrose, L Wirthlin, M Creer, P Herrbrich, T Craft, Nolta J. Functional characterization of highly purified human hematopoietic repopulating cells isolated based on aldehyde dehydrogenase activity. Blood, Sept.104:1648-55, 2004. Smith E, Meyerrose T, Kohler T, Nolta JA, Muller R, Bab I, Frenkel B. Leaky ribosomal scanning in mammalian genomes: significance of histone H4 alternative translation in vivo. Nucleic Acids Res. Mar 01;33(4):1298-308, 2005. Sohara Y, Shimada H, Minkin C, Erdreich-Epstein A, Nolta JA, DeClerck YA. Bone marrow mesenchymal stem cells provide an alternate pathway of osteoclast activation and bone destruction by cancer cells. Cancer Res. Feb 15; 65: 1129-35, 2005. Hess DA, Wirthlin L, Craft T, Hohm S, Lahey R, Eades WC, Creer MH, Nolta JA. Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells. Blood, March 1; 107(5):2162-9, 2006. Dao MA and Nolta JA. Cytokine and integrin stimulation synergize to promote higher levels of GATA-2, c-myb, and CD34 protein in primary human hematopoietic progenitors from bone marrow. Blood.109(6):2373-9, Mar 15, 2007. Meyerrose TE, DeUgarte DA, Hofling A, Herrbrich P, Sands MS, Hedrick MA, and Nolta JA. In vivo Distribution of Adipose-Derived Mesenchymal Stem Cells in Novel Xenotransplant Models. Stem Cells.; 25; 220-227, 2007. Partlow KC, Brant J, Chen J, Meyerrose TE, Nolta JA, Caruthers S, Lanza G, and Wickline SA. 19F magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons. FASEB J. Jun;21(8):1647-54, 2007. Hess DA, Bonde J, Wirthlin L, Dipersio J, Devine S, Nolta J. Human progenitors rapidly mobilized by AMD3100 repopulate NOD/SCID mice with increased efficiency compared to G-CSF-mobilized cells. Biol.Blood MarrowTransplnt 13:398-411, 2007. Dao MA, Nolta JA, Creer MH, Verfaillie CM. Biology of umbilical cord blood progenitors in bone marrow niches. Mar 19. Blood Jul 1;110(1):74-81, 2007. S X. Qiu, C Dan, L-S Ding, S Peng, S-N Chen, N Farnsworth, J Nolta, M Gross, Ping Zhou. A Triterpene Glycoside from Black cohosh that Inhibits Osteoclastogenesis by Modulating RANKL and TNF Signaling Pathways. Chem Biol. 14:860-9, 2007. B. Nervi, M. Rettig, J. Ritchey, J. Nolta, G. Bauer, J. DiPersio. A new model for GvHD: naïve and ex-vivo activated human T cells generate consistent engraftment and lethal disease in NOD/SCID/B2M null mice. Exp Hem. Dec;35(12):1823-38, 2007. D. Maxwell, J. Bonde, D. Hess, M. Creer, R. Lahey, D. Piwnica-Worms, and J. Nolta. Fluorophore-conjugated iron oxide nanoparticle labeling and analysis of engrafting human stem cells. Stem Cells. Feb;26(2):517-24. 2008. D. Hess, T. Craft, L. Wirthlin, W. Eades, M. Creer, M. Sands, J. Nolta. Widespread nonhematopoietic tissue distribution by transplanted human progenitor cells with high aldehyde dehydrogenase activity. Stem Cells. Mar;26(3):611-20. 2008. G Bauer, M Dao, S Case, P Herrbrich, J Arevalo, T Meyerrose, X Wang, S Csik, D Skelton, D B. Kohn, and J Nolta. In Vivo Biosafety Model to Assess Risk of Adverse Events from Retroviral and Lentiviral Vectors. Mol Ther. Jul;16(7):1308-15, 2008. T Meyerrose, M Roberts, K Ohlemiller, C Vogler, L Wirthlin, J Nolta, M Sands. Lentiviral-transduced human mesenchymal stem cells persistently express therapeutic levels of enzyme in a xenotransplant model of human disease. Stem Cells.26:1713-22. 2008. 62. Zhou P, Hohm S, Capoccia B, Link D, and Nolta JA. Immunodeficient mouse models to study human stem-cell mediated repair of tissue injury. Methods Mol Biol; 430:213-25, 2008. 63. J.Rich, I. Rosova, J. Nolta, T. Myckatyn, L. Sandell, A. McAlinden. Upregulation of Runx2 and Osterix during in 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. vitro chondrogenesis of human adipose-derived stromal cells. Biochem Biophys Research Com. Jul 18;372(1):230-5. 2008. Rosová I, Dao MA, Capoccia BJ, Link DC, Hess DA, Nolta JA. Hypoxic Preconditioning Results in Increased Motility and Improved Therapeutic Potential of Human Mesenchymal Stem Cells. Stem Cells. Aug;26(8):2173-82. 2008. Anderson JS, Javien J, Nolta JA, Bauer G. Preintegration HIV-1 Inhibition by a Combination Lentiviral Vector Containing a Chimeric TRIM5alpha Protein, a CCR5 shRNA, and a TAR Decoy. Mol Ther. 17(12):2103-14. 2009. Anderson J, Nolta JA, Bauer G. Specific Transduction of HIV-Susceptible Cells for CCR5 Knockdown and Resistance to HIV Infection: A Novel Method for Targeted Gene Therapy and Intracellular Immunization. J Acquir Immune Defic Syndr. Oct 1;52(2):152-61. 2009. P. Zhou, L. Wirthlin, J. McGee, G. Annett, and J. Nolta. Contribution of human hematopoietic stem cells to liver repair. Seminars in Immunopathology Sep;31(3):411-9. Epub 2009 Jun 17.2009. P. Zhou, R. Lahey, S. Hohm, D. Hess, J Nolta. Human progenitor cells with high aldehyde dehydrogenase activity efficiently engraft into damaged liver in a novel model. Hepatology 49 (6): 1992 – 2000, 2009. Capoccia BJ, Robson DL, Levac KD, Maxwell DJ, Hohm SA, Neelamkavil MJ, Bell GI, Xenocostas A, Link DC, Piwnica-Worms D, Nolta JA, Hess DA. Revascularization of ischemic limbs after transplantation of human bone marrow cells with high aldehyde dehydrogenase activity. Blood 21 May, 113 ( 21): 5340-5351, 2009. P Zhou, S Gross, J-H Liu, B-Y Yu, LL Feng, JA Nolta, V Sharma, D Piwnica-Worms and SX Qiu. Flavokawain B, the Hepatotoxic Constituent from Kava Root, Induces GSH-Sensitive Oxidative Stress through Modulation of IKK/NF-κB and MAPK Signaling Pathways. FASEB J. Dec;24(12):4722-32, 2010. I. Rosová, D. Link, and Nolta J. Small Interfering RNA-Mediated Decreases in c-Met Levels Affect the Differentiation Potential of Human Mesenchymal Stem Cells and Reduce Their Capacity for Tissue Repair. Tissue Engineering Aug;16(8):2627-39, 2010. Sondergaard CS, Hodonsky CJ, Khait L, Shaw J, Sarkar B, Birla R, Bove E, Nolta J, Si MS. Human Thymus Mesenchymal Stromal Cells Augment Force Production in Self-Organized Cardiac Tissue. Ann Thorac Surg. Sep; 90(3):796-804, 2010. C Sondergaard, D Hess, D Maxwell, I Rosová, D Piwnica-Worms, A Kovacs, L Pedersen, and J Nolta. Human UCB Progenitors with High ALDH Activity Improve Vascular Density in Acute Myocardial Infarction. J. Translational Medicine. 8:24-9, 2010. Zhou P, Estrada, D, Lingala S, Zern M, Nolta, J, Wu, J. Decellularized Liver Matrix as a Carrier for Transplantation of Human Fetal and Primary Hepatocytes in Mice. Liver Transplantation; 17(4):418-27. 2010. Joyce N, Annett G, Wirthlin L, Olson S, Bauer G, Nolta J. Mesenchymal stem cells for the treatment of neurodegenerative disease. Regenerative Medicine Nov; 5(6):933-46, 2010. Kambal A, Mitchell G, Cary W, Gruenloh W, Jung Y, Kalomoiris S, Nacey C, McGee J, Lindsey M, Fury B, Bauer G, Nolta JA, Anderson JS. Generation of HIV-1 Resistant and Functional Macrophages From Hematopoietic Stem Cell-derived Induced Pluripotent Stem Cells. Molecular Therapy Mar; 19(3):584-93, 2011. Chen X, Lingala S, Zern M, Nolta J., Wu J. Epithelial mesenchymal transition and hedgehog signaling activation are associated with chemoresistance and invasion of hepatoma subpopulations. J. Hepatology;55(4):838-45, 2011. Meyerrose T, Olson S, Pontow S, Kalomoiris S, Jung Y, Annett G, Bauer G, Nolta JA. Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors. Advances in Drug Delivery Reviews 62 (12) 1167-74, 2010. Gruenloh W, Kambal A, Sondergaard C, McGee J, Nacey C, Olson S, Fierro F, Nolta JA, Characterization and In Vivo Testing of Mesenchymal Stem Cells Derived From Human Embryonic Stem Cells. Tissue Engineering 17 (11) 1517-25, 2011. Fierro FA, Kalomoiris S, Nolta JA. Effects on proliferation and differentiation of multipotent mesenchymal stromal cells over-expressing growth factors for combined gene/cell therapy. Stem Cells 29(11):1727-37, 2011. Jun-feng Feng, Jing Liu, Xiu-zhen Zhang, Lei Zhang, Ji-yao Jiang, Jan Nolta, Min Zhao. Guided Migration of Neural Stem Cells Derived from Human Embryonic Stem Cells by an Electric Field. Stem Cells. Feb; 30(2):349-55, 2012. Y Jung, G Bauer, and J Nolta. Induced pluripotent stem cells and mesenchymal stem cells: progress toward safe clinical products. Stem Cells. Jan;30(1):42-7, 2012. Murphy WJ, Nolta JA. Autoimmune T Cells Lured to a FASL Web of Death by MSCs. Cell Stem Cell. May 4;10(5):485-7, 2012. Kumari R, Li H, Haudenschild DR, Fierro F, Carlson CS, Overn P, Gupta L, Gupta K, Nolta J, Yik JH, Di Cesare PE. The oncogene LRF is a survival factor in chondrosarcoma and contributes to tumor malignancy and drug resistance. Carcinogenesis. Nov;33(11):2076-83, 2012. 85. Mathews G, Sondergaard C, Jeffreys A, Childs W, Le B, Sahota A, Najibi S, Nolta J, Si MS. Computational Analysis of Contractility in Engineered Heart Tissue. IEEE Trans Biomed Eng. May; 59(5):1429-35, 2012. 86. Walker JE, Chen RX, McGee J, Nacey C, Pollard RB, Abedi M, Bauer G, Nolta JA, Anderson JS. Generation of an HIV-1-resistant immune system with CD34(+) hematopoietic stem cells transduced with a triple-combination antiHIV lentiviral vector. J Virol. May; 86(10):5719-29, 2012. 87. Park SS, Caballero S, Bauer G, Shibata B, Roth A, Fitzgerald PG, Forward KI, Zhou P, McGee J, Telander DG, Grant MB, Nolta JA. Long-Term Effects of Intravitreal Injection of GMP-Grade Bone-Marrow-Derived CD34+ Cells in NOD-SCID Mice with Acute Ischemia-Reperfusion Injury. Invest Ophthalmol Vis Sci.; 53(2):986-94, 2012. 88. S Olson, K Pollock, A Kambal, W Cary, G Mitchell, J Tempkin, H Stewart, J McGee, G Bauer, T Tempkin, V Wheelock, G Annett, G Dunbar and J Nolta, Genetically Engineered Mesenchymal Stem Cells as a Proposed Therapeutic for Huntington’s disease. Molecular Neurobiology;45(1):87-98, 2012. 89. Kalomoiris S, Lawson J, Chen RX, Bauer G, Nolta JA, Anderson JS. CD25 Preselective Anti-HIV Vectors for Improved HIV Gene Therapy. Hum Gene Ther Methods. 2012 Dec; 23(6):366-75. 90. S Olson, A Kambal, K Pollock, G Mitchell, H Stewart, S Kalomoiris, W Cary, C Nacey, K Pepper, J Nolta. Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin. Molecular and Cellular Neuroscience;49(3):271-81, 2012. 91. Liu J, Githinji J, McLaughlin B, Wilczek K, Nolta J. Role of miRNAs in Neuronal Differentiation from Human Embryonic Stem Cell-Derived Neural Stem Cells. Stem Cell Rev;8(4):1129-37, 2012. 92. Liu J, Koscielska KA, Cao Z, Hulsizer S, Grace N, Mitchell G, Nacey C, Githinji J, McGee J, Garcia-Arocena D, Hagerman RJ, Nolta J, Pessah I, Hagerman PJ. Signaling defects in iPSC-derived fragile X premutation neurons. Hum Mol Genet. 21(17):3795-805. 2012. 93. M Guan, R Liu, K Lam, J Lou, Nolta J, B Panganiban, R Ritchie, N Lane, W Yao. Directing mesenchymal stem cells to bone to increase bone formation. Nature Medicine; 18(3):456-62, 2012. 94. Annett G, Bauer G, Nolta JA. Mesenchymal stem cells for trinucleotide repeat disorders. Methods Mol Biol. 1010:79-91, 2013. 95. Ma X, Duan Y, Tschudy-Seney B, Roll G, Behbahan IS, Ahuja TP, Tolstikov V, Wang C, McGee J, Khoobyari S, Nolta JA, Willenbring H, Zern MA. Highly Efficient Differentiation of Functional Hepatocytes From Human Induced Pluripotent Stem Cells. Stem Cells Transl Med. May 16. [Epub ahead of print] 2013. 96. NL Magner, Y Jung, J Wu, JA Nolta, MA Zern, and P Zhou. Insulin and IGFs Enhance Hepatocyte Differentiation from Human Embryonic Stem Cells via the PI3K/AKT Pathway. Stem Cells. 2013 Oct;31(10):2095-103. 97. Plowman EK, Bijangi-Vishehsaraei K, Halum S, Cates D, Hanenberg H, Domer AS, Nolta JA, Belafsky PC. Autologous myoblasts attenuate atrophy and improve tongue force in a denervated tongue model: A pilot study. Laryngoscope. 2013 Aug 8. 124(2): 20-6. PMID:23929623 98. Yao W, Guan M, Jia J, Dai W, Lay YA, Amugongo S, Liu R, Olivos D, Saunders M, Lam K, Nolta J, Olvera D, Ritchie RO, Lane NE. Reversing Bone Loss by Directing Mesenchymal Stem Cells to the Bone. Stem Cells. 2013 Jul 2. doi: 10.1002/stem.1461. [Epub ahead of print]. 99. Binder BY, Sondergaard CS, Nolta JA, Leach JK. Lysophosphatidic Acid enhances stromal cell-directed angiogenesis. PLoS One. 2013 Dec 2;8(12):e82134. doi: 10.1371/journal.pone.0082134 100. Gericota B, Anderson JS, Mitchell G, Borjesson DL, Sturges BK, Nolta JA, Sieber-Blum M. Canine Epidermal Neural Crest Stem Cells: Characterization and Potential as Therapy Candidate for a Large Animal Model of Spinal Cord Injury. Stem Cells Transl Med. 2014 Jan 17. [Epub ahead of print] 101. Dasu MR, Ramirez SR, La TD, Gorouhi F, Nguyen C, Lin BR, Mashburn C, Stewart H, Peavy TR, Nolta JA, Isseroff RR. Crosstalk Between Adrenergic and Toll-Like Receptors in Human Mesenchymal Stem Cells and Keratinocytes: A Recipe for Impaired Wound Healing. Stem Cells Transl Med. 2014 Apr 23. [Epub ahead of print] 102. Perez-Cunningham J, Ames E, Smith RC, Peter AK, Naidu R, Nolta JA, Murphy WJ. Natural killer cell subsets differentially reject embryonic stem cells based on licensing. Transplantation. 2014 May 27;97(10):992-8. 103. Osborn SL, Thangappan R, Luria A, Lee JH, Nolta J, Kurzrock EA. Induction of human embryonic and induced pluripotent stem cells into urothelium. Stem Cells Transl Med. 2014 May;3(5):610-9. 104. Satake N, Duong C, Chen C, Barisone GA, Diaz E, Tuscano J, Rocke DM, Nolta J, Nitin N. Targeted therapy with MXD3 siRNA, anti-CD22 antibody and nanoparticles for precursor B-cell acute lymphoblastic leukaemia. Br J Haematol. 2014 Sep 8. doi: 10.1111/bjh.13066. [Epub ahead of print] 105. McMahill BG, Borjesson DL, Sieber-Blum M, Nolta JA, Sturges BK. Stem Cells in Canine Spinal Cord Injury Promise for Regenerative Therapy in a Large Animal Model of Human Disease. Stem Cell Rev. 2014 Aug 31. [Epub ahead of print] Books, Invited Articles, and Chapters (Selected, of over 30) 1. Meyerrose TM, Herrbrich P, Wang X, Dao MA, Nolta JA. Pluripotent human stem cell analysis in immune deficient mice. The Pluripotential Hematopoietic Stem Cell, Editor: J. Keller. Eurekah Press, 2003. 2. Meyerrose TE, Herrbrich P, Hess DA, Nolta JA. Immune-deficient mouse models for analysis of human stem cells. Biotechniques. Dec; 35 (6):1262-72, 2003. 3. Meyerrose T, Rosova I, Dao M, Bauer G, and Nolta JA. Establishment and transduction of primary human mesenchymal stem cell monolayers. Chapter 2 in Genetic Engineering of Mesenchymal Stem Cells. Kluwer, pp 4558. Nolta JA (Editor). Feb 2006. 4. FA. Fierro, J Egana, C Toupadakis, C Yellowley, H Machens, JA Nolta. Small Animal models of tissue regeneration. Chapter 20 in Stem Cell Biology and Regenerative Medicine. H. Bernstein (Editor), 2011. 5. Armstrong L, Lako M, Buckley N, Lappin TR, Murphy MJ, Nolta JA, Pittenger M, Stojkovic M. Our top 10 developments in stem cell biology over the last 30 years. Stem Cells. Jan; 30(1):2-9, 2012. 6. Y Jung, G Bauer, and J Nolta. Induced pluripotent stem cells and mesenchymal stem cells: progress toward safe clinical products. Stem Cells. Jan; 30(1):42-7, 2012. 7. Nolta JA. Editorial: 2013 - a year of clinical success and great scientific innovation in the stem cell field. Stem Cells. 2014 Jan; 32(1):1-2. PMID:24375745 8. Lee JK, Responte DJ, Cissell DD, Hu JC, Nolta JA, Athanasiou KA. Clinical translation of stem cells: insight for cartilage therapies. Crit Rev Biotechnol. 2014 Mar; 34(1):89-100. PMID: 24083452 9. Concise review: MicroRNA function in multipotent mesenchymal stromal cells. Clark EA, Kalomoiris S, Nolta JA, Fierro FA. Stem Cells. 2014 May;32(5):1074-82. PMID: 24860868 10. G Annett, G Bauer and J Nolta. Mesenchymal Stem Cells for Trinucleotide Repeat Disorders. Chapter 12 in Trinucleotide Repeat Protocols, Second Edition, edited by Kohwi and McMurray, 2013. Relevant Investigator-initiated INDs/Clinical Trials (blue-NIH-RAC numbers for gene therapy trials, Nolta subinvestigator): 0301-566 Infusion of Genetically Modified T cells: Tracking and Toxicity (DiPersio) 0602-758 Lentiviral-Mediated Gene Therapy for MPS VII (Sands) 9306-047 Retroviral Mediated Transfer of the cDNA for Human Glucocerebrosidase into Stem Cells of Patients with Gaucher Disease. (Kohn) NCT00794508: Transduction of CD34+ Cells from Children with Adenosine Deaminase (ADA)-Deficient SCID (Kohn) NCT00871702: Infusion of Genetically Modified T Cells for Post-Transplant Patients with Relapsed Disease (DiPersio) FDA IND: BB IND# 13065. Stem Cell Implantation in Elderly Patients Undergoing CABG (Rich) FDA IND: BB IND# 14848. Infusion of autologous cord blood for traumatic brain injury FDA IND: BB IND# 13307. A Pilot Clinical Trial of the Feasibility and Safety of Intravitreal Autologous Adult Bone Marrow Stem Cells in Treating Eyes With Vision Loss From Retinopathy (Park). Patent Applications/Patents - Mesenchymal Stem Cells producing inhibitory RNA for disease modification. ROI 2008. UC Patent 2009-170-1; Ref.: 060933-4300. Inventors: Scott Olson, Ph.D., Louisa Wirthlin, B.S., Jan Nolta Ph.D. International Filing 2009. - Combination anti-HIV vectors, targeting vectors, and methods of use. PCT/US2010/033042. Inventors J. Anderson, G. Bauer, Jan Nolta, 2009. - EIIIA and EIIIB segments of fibronectin regulate stem cell fate. 060933-5650. S.Pontow, J. Peters, Jan Nolta. 2010. - HIV resistant immune system cells from induced pluripotent stem cells. J. Anderson, G. Bauer, Jan Nolta, ROI 2010 - Decellularized liver matrix and iPSC-derived hepatocytes for liver bioengineering. J. Wu, P. Zhou, J Nolta, ROI 2010. - Genetically modified MSC and therapeutic methods. Fernando Fierro, Karen Pepper, Gerhard Bauer and Jan Nolta, PCT International application no. PCT/US2013/057721, filed on August 30, 2013. -Vectors and Methods to Treat Ischemia. Fernando Fierro, Karen Pepper, Gerhard Bauer and Jan Nolta, PCT International application no. PCT/US2014/029386, filed on March 14, 2014 Jan A. Nolta, Ph.D. - Research Projects - Active: 1) 1R01GM099688-01 (Nolta) 07/01/2011 - 06/30/2016 $2,700,217 total 1.8 months effort NIH Common fund transformative research projects program Direct cell to cell transfer of microRNA for tissue repair. The studies will examine the use of human mesenchymal stem cells to deliver microRNA and other key factors to damaged tissues to hasten repair. 2) CIRM DR2A-05415 (Wheelock PI/Nolta Co-PI) 11/01/12-10/31/16 $18,950,059 (clinical trial) 1.8 mo effort MSC engineered to produce BDNF for the treatment of Huntington's disease. This award is to prepare and conduct a Phase I clinical trial of human Mesenchymal Stem Cells engineered to express brain – derived neurotrophic factor for patients with early stage Huntington’s disease. It is based on preclinical data demonstrating the safety and efficacy of this approach in rodent and non-human primate models. The goal is to restore striatal brain volume and to reduce levels of movement and cognitive decline in HD patients. 3) CIRM DR2A-05423 (Laird PI/Nolta co-PI) 11/01/12 – 10/31/16 $14,184,594 total (clinical trial) 1.8 mo effort Phase I study of IM Injection of VEGF Producing MSC for the Treatment of Critical Limb Ischemia. This award is to prepare and conduct a Phase I clinical trial of human Mesenchymal Stem Cells engineered to express VEGF for patients with end-stage critical limb ischemia. The goal is to prevent amputation of limbs. 4) TR2-01787: CIRM (Isseroff PI, Nolta Co-PI) 02/01/11-01/31/14 $4,526,900 total 1.8 months (15%) Bone Marrow Mesenchymal Stem Cells to Heal Chronic Diabetic Wounds The goal of the proposed studies is to move a development candidate composite stem cell/ decellularized matrix construct to the clinic for non-healing ulcers in diabetic patients seen in Dr. Isseroff’s wound care clinic at the VA hospital. 5) RB4-05764 (PI-Lieu, Co-Investigator/mentor Nolta) California Institute for Regenerative Medicine 2/1/13 – 1/31/16 $355,680/yr 0.6 cal mos. Induction of pluripotent stem cell-derived pacemaking cells. This proposal studies the mechanisms of cardiac cell differentiation from human induced pluripotent stem cells to generate biopacemakers. 6) TB1-01184: CIRM (Trainer, Jill PI, Nolta UC Davis lead mentor) 10/01/09 – 09/31/14 0.48 months (4%) Bridges to Stem Cell Research Training Program. Bridges is an innovative collaborative program between California State University Sacramento (CSUS) and UC Davis to train state college Master’s Program interns in the practical aspects of stem cell biology, good manufacturing practices, good laboratory practices, and Cellular therapy. Subcontract Previous Grants 7) CIRM FA-00611-1: Institutional grant: Nolta, designated contact, $20,083,000 CIRM Major Facilities Grant: this award was for “Bricks and Mortar” and equipment for renovation of the new UC Davis/CIRM Institute for Regenerative Cures, which is now the hub for the large UC Davis stem cell program (currently over 150 faculty members). 8) TR1-01257: CIRM (Nolta) 08/01/09-10/31/12 $2,753,559 total Sustained siRNA production from human MSC to treat Huntington’s disease and other neurodegenerative disorders. Develop a novel MSC-based stem cell therapy to treat Huntington's disease, leading toward clinical trials. This work is continuing and currently funded by the NIH Office of the Director. 9) 2RO1DK61848 (Nolta), NIH NIDDK 09/30/01 – 06/30/11 $250,000 DC/ yr. Immunodeficient mouse model of stem cell plasticity. The goal of the proposed studies was to develop immune deficient mouse models to track the origin of blood and liver cells, to determine whether a common progenitor existed. A common stem cell precursor could have been validated by the single cell clonal integration analysis techniques developed in the Nolta lab. The work resulted in several reports that, through careful clonal marking studies, the adult blood and liver stem cells were in fact demonstrated to be distinct. 10) RN1-00561: CIRM (Chong Pan PI, Nolta Co-mentor) 2008-2013 $300,000 DC/yr 0.6 months (5%) Combinatorial Chemistry Approaches to Develop Ligands to Leukemia Stem Cells. Dr. Nolta was Dr. Chong’s stem cell mentor. This work resulted in several potential drugs, now in the patent process. 11) RM1-01724: CIRM (Murphy PI, Nolta co-investigator) 2010-2013 $154,807/yr 1.2 months (10%) effort Natural killer (NK) cells as “veto” cells to promote donor-specific tolerance. Develop methods to tolerize recipients to engrafted tissues by the use of donor NK cells. This work is ongoing and leading toward clinical trials at UCD with an industry partner. 12) TR2-01857: CIRM (Zern PI, Nolta Co-Investigator) 2011-2013 $1,271,316/yr 1.2 months (10%) effort Liver Cell Transplantation. Establish human ESCs as a source of hepatocytes for the future planned therapy of patients with liver failure. This work is now being continued by Co-PI Dr. Willenbring at UCSF. 13) 1RO1 HL073256-01 (Nolta) NIH NHLBI 07/01/03 - 06/30/12 $250,000 DC/yr 1.8 months (15%) Effort Functional Dissection of human adipose-derived MSC and bone marrow-derived MSC phenotypes. The goal was to identify the most primitive subsets of primary human MSC and to determine the functional differentiative potential of each defined subset and the homing and tissue regenerative potential in immune deficient mice. The standard operating procedures for human MSC expansion and transduction resulting from this funding are now used in the CMC section for multiple IND applications at UC Davis. These SOPs form the basis of the cellular product for the CIRM disease team grant and proposed trial “Phase I study of IM Injection of VEGF Producing MSC for the Treatment of Critical Limb Ischemia.” 14) 2P51RR000169-49. Stem Cell Therapies for Huntington’s disease 2011-2012 To conduct IND-enabling studies with the UC Davis Clinical Translational Science Center (CTSC) in support of a stem cell clinical trial for HD. Non-human primate biosafety studies were conducted. These data provided preliminary evidence of safety for CIRM grant DR2A-05415 “MSC engineered to produce BDNF for the treatment of Huntington's disease”. 15) RB2-01567: CIRM (Kurzrock PI, Nolta co-PI) 2010-2013 $ 441,360/yr DC 0.6 months (5%) Differentiation of Human Stem Cells into Urothelium. The goal is to develop bladder tissue replacement constructs for patients with cancer and spin bifida, both causing loss or absence of functional bladder tissue. This project is ongoing and currently funded by Shriner’s Hospital of Northern California. 16) 5RC1AG036022-02: ARRA Challenge grant (Hagerman PI, Nolta, Pesseh co-Is) 10/2009 -09/2011 $999,924.00 Human iPSC neuronal models for FXTAS neurodegeneration. Generate induced pluripotent stem cells from the fibroblast cell lines from the consented FXTAS patients seen by the Hagermans and to study the potential signaling deficits from neurons derived from each pluripotent cell line, in comparison to unaffected controls. 17) 1S10RR026825-01 (Nolta) NIH NCRR 01/26/10 $499,785 Shared LSRII Cytometer Equipment Application – this award funded a shared cytometer for the Stem Cell Program’s Sorter Core in the new Institute for Regenerative Cures. The instrument is used heavily in the Institute’s Flow core. 18) 5P30AG010129 - 19 (DeCarli, PI, Nolta - Pilot grant PI) 10/09-09/10 $34,000 The goal of this pilot project on Dr. DeCarli’s center grant was for Dr. Nolta to mentor Dr. Olson in her lab, who will investigate the use of human MSC to deliver biotherapeutics for Alzheimer’s disease directly into the brain tissue. 19) 1R01HL073762-01 (Link), NIH NHLBI 07/01/03 – 06/30/07 $250,000 DC/yr Stem Cell Mobilization to enhance tissue repair. Regimens to mobilize murine hematopoietic, mesenchymal, and endothelial progenitors capable of mediating repair of damaged cardiac tissue were determined. 20) 2R01DK53041 (Nolta), NIH NIDDK 09/30/97 - 04/30/07 $250,000 DC/yr Ex-vivo Stem Cell Manipulation and Human Hematopoiesis. Promote primitive human hematopoietic progenitor survival and self-renewal in vitro, determine molecular changes that precede lineage commitment in human stem cells. 21) HL54850-02 (Nolta), NIH NHLBI 1/1/01 - 12/31/06 $242,000 DC/yr Specialized Center of Research (Parkman), Project 2 (Nolta); In vivo model for human stem cells. Examine transduction, in vivo differentiation, and the molecular aspects of cell cycle regulation in human hematopoietic stem cells. The results of this study, and SOPs developed, were used in several clinical trials of gene-modified hematopoietic stem cells done at Children’s Hospital Los Angeles, to treat children with Primary Immune Deficiencies, including “NCT00794508 Transduction of CD34+ Cells from Children with Adenosine Deaminase (ADA)-Deficient SCID (Kohn)”. 22) 1R21DK62892-01 (Nolta) NIH NIDDK 03/01/03 – 02/28/06 $100,000 DC/ yr. HGF (Hepatocyte growth factor) induces robust human thymopoiesis in mice The goal was to produce better xenograft models in which to examine human T cell reactivity. The models are now used by the UC Davis HIV team researchers, who have just submitted an IND to the FDA for their pending clinical trial, “Stem Cell Gene Therapy for HIV Mediated by Lentivector Transduced, Pre-selected CD34+ Cells.”