BIOGRAPHICAL SKETCH
NAME: Jan A. Nolta, Ph.D. / POSITION TITLE:Professor, Director of the Stem Cell Program,
University of California, Davis
eRA COMMONS USER NAME: Jnolta
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION / DEGREE / YEAR(s) / FIELD OF STUDYCalifornia State University Sacramento, CA B.S.1984Biology
University of Southern California, L.A., CA Ph.D.1994Microbiology
Childrens Hospital of Los Angeles, CAPost-Doc1996Gene Therapy / B.S.1984Biology
Ph.D.
PostdocPost-Doc1996Gene Therapy / 1984
1990-94
1994-97 / Biology
Molecular Microbiology
Stem Cell Gene Therapy
Professional Experience and Duties:
Professor, Director of the Stem Cell Program, 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, - Section of Hematopoietic Development and Malignancy (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, 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)
Cytogenetics Laboratory, UC Davis Medical School (1985-87)
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)
Activities:
Member: American Society of Hematology, AAAS, International Society of Experimental Hematology; American Society for Gene Therapy, International Society for Stem Cell Research (ISSCR)
International Society for Hematology and Graft Engineering (ISHAGE) Gene Therapy Committee (1998-99)
Moderator/ session chair at the Annual Meeting of the American Society for Hematology (1997 – 2007)
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 Therapy, Hematopoietic Therapy committee, 2003-present. Chair, 2004-2006
Editorial Board, Human Gene Therapy, 2001-2008, Editorial Board, Experimental Hematology, 2000 – present
Section Editor, Leukemia: stem cells, August 2001 - 2002. Editorial Board, Leukemia June 1999- Nov. 2005.
Editorial Board, Blood, September 2002 – present
Editorial Board, Molecular Therapy, 2003- 2005.
Section Editor, Leukemia, Nov. 2000 – 2006 (Gene Therapy Section)
Full Member, Hematology B Study Section, National Institutes of Health, May 2003-June 2007.
Chair, New York Stem Cell Research Program (NYSTEM) Shared Facilities/Resources Panel, 2008
Associate Editor, Stem Cells, February 2008 - present.
Publications (Selected, of 85 peer-reviewed manuscripts)
1. Nolta JA, Kohn DB. Expression of hu GC in murine LTBMC 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 50:1455-58,1990.
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 4-HC 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 vector-mediated 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 83:3041-3051, 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. Nolta JA, Kohn DB. Hematopoietic stem cells for gene therapy. In Stem Cells, Ed: C. Potten, Academic Press, pp. 447-61, 1996.
17. 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. 3:81-90, 1997.
18. Dao MA, Hannum CH, and Nolta JA. FLT3 ligand preserves the ability of human CD34+ progenitors to sustain long-term hematopoiesis in immune deficient mice following ex-vivo retroviral - mediated transduction. Blood 89:446-456, 1997.
19. 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.
20. 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.
21. 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.
22. Dao M, Nolta JA. Hematopoietic stem cells as targets for Gene Therapy: Cancer Research, Therapy and Control 7:19-25, 1998.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
Publications, continued
30. 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.
31. Dao, MA and Nolta JA. CD34: To select or not to select? That is the question. Leukemia 14: 773-776, 2000.
32. Parkman R, Weinberg K, Crooks G, Nolta J, Kohn D. Gene therapy for ADA deficiency. Ann. Rev. Med. 51:33-47, 2000.
33. Evans M, Jordan C, Nolta, JA, Wivel N et al. Clinical Infection Control in Gene Therapy. Infection Control 21: 659 – 673, 2000.
34. 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.
35. 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.
36. 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.
37. Nolta JA. Cell - Based Therapy: will it replace pharmaceuticals in some cases? Current Drugs 4:212-218, 2002
38. 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.
39. 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.
40. 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.
41. 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.
42. Bauer G, Nolta JA, Walker JE, Devine S, DiPersio J. Design and construction of a GMP facility for cellular and gene therapy in an academic center-implementing new regulatory requirements. Stem Cell and Cellular Therapy 1:54-61, 2003.
43. 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.
44. 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.
45. 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
46. 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.
47. J Bonde, D Hess, J Nolta. Recent advances in hematopoietic stem cell biology. Curr Opin Hematol. Nov;11(6):392-8, 2004.
48. 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.
49. 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.
50. 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.
51. 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.
52. 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.
53. 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.
54. 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.
55. 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.
56. 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.
57. 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.
58. 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.
59. 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.
60. 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.
61. 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.
62. 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.
63. P Zhou, S Gross, J Liu, J Nolta, S Qiu and D Piwnica-Worms. Flavokawain B, the Hepatotoxic Constituent from Kava Root, Induces GSH-Sensitive Oxidative Stress Through Modulation of IKK/NF-kB and MAPK Signaling Pathways. Submitted, 2008.
64. Capoccia BJ, Hohm SA, Wirthlin L, Shepherd R, Link DC, Nolta JA, Hess DA. Human BM-derived aldehyde dehydrogenase-expressing cells possess endothelial progenitor function and augment revascularization after acute ischemic injury. MS Sub, 2008.
65. 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.
66. P. Zhou, R. Lahey, S. Hohm, D. Hess, J Nolta. Liver Engraftment by Transplanted Human Cord Blood Progenitors and Human embryonic Stem Cells in a Novel Model, the NOD/SCID/MPSVII Mouse. Submitted after revision, 2008.
67. CS Sondergaard , D Hess, D Maxwell, C Weinheimer, I Rosová, M Creer, D Piwnica-Worms, A Kovacs, L Pedersen, and J A Nolta. Human Cord Blood Progenitors with High Aldehyde Dehydrogenase Activity Improve Vascular Density in a Model of Acute Myocardial Infarction. Submitted after revision, 2008.
68. J.Rich, I. Rosova, J. Nolta, T. Myckatyn, L. Sandell, A. McAlinden. Upregulation of Runx2 and Osterix during in vitro chondrogenesis of human adipose-derived stromal cells. Biochem Biophys Research Com. Jul 18;372(1):230-5. 2008.
69. 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.
Recent Books, Invited Articles, and Chapters (Selected, 5 of 20)
- Dao MA, Nolta JA. Retroviral - mediated transduction of human hematopoietic stem and progenitor cells. Hematopoietic Stem Cell Protocols, Chapter 17, P. 253-274. Editors. C. Jordan and C. Klug. The Humana Press Inc., Totowa, NJ 2002.
- 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.
- 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.
- 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 45-58. Nolta JA (Editor). Feb 2006.
- Bonde J, Nolta J, Human hematopoietic cell culture, transduction, and analyses. Curr Protoc Hum Genet. Chap 13, 2008.
Research Projects Ongoing or Completed During the Last Three years
1) 2RO1DK61848 (Nolta), NIH NIDDK09/30/01 – 06/30/10 $250,000 DC/ yr. 25% effort
Immunodeficient mouse model of stem cell plasticity
The goal of the proposed studies is to develop immune deficient mouse models in which the existence of marrow – derived stem cells capable of generating both blood and liver can be rigorously demonstrated by single cell clonal integration analysis.
2) 1RO1 HL073256-01 (Nolta)NIH NHLBI04/01/03 - 03/31/09 $250,000 DC/yr25% Effort
Functional Dissection of human adipose-derived MSC and bone marrow-derived MSC phenotypes. The goal is 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. On no-cost extension: Competitive renewal pending.
3) California Institute for Regenerative Medicine FA-00611-1: Institutional grant: Nolta, designated contact$20,083,000
CIRM Major Facilities Grant: this award is for “Bricks and Mortar” and equipment for renovation of the new UC Davis/CIRM Stem Cell Institute, which will house the rapidly growing UC Davis stem cell program (currently over 120 faculty members).
4) 1T35DK083263-01: Introduction to Cellular Therapy for Students in Health Care Professions (Nolta, NIH NIDDK;pending). The goal of the T-35 is to give students an introduction to the process of moving promising research from the bench to the bedside.