Prof. Lung-Ji Chang |
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University of Florida College of Medicine Molecular Genetics and Microbiology Department ProfessorAppointed: 2007 University of Florida College of Medicine Molecular Genetics and Microbiology Powell Gene Therapy Center and McKnight Brain Institute Professor |  |
Mailing AddressBox 100266, Room R1-252, ARB Department of Molecular Genetics & Microbiology Powell Gene Therapy Center McKnight Brain Institute Gainesville, Florida 32610-0266United States | Contact Information |
Qualifications
Ph.D., University of Iowa, Microbiology, 1986.
B.Sc., National Taiwan University, 1980.
Expertise and Research Interests
Development of novel gene transfer vectors, preclinical models, and therapeutic strategies for HIV/AIDS, genetic diseases and cancer
Specific:
Retroviruses are RNA viruses that synthesize DNA from the viral RNA genome and then integrate into the host cell genome by a process called reverse transcription and integration. My research has been focused on the study of gene regulation of retroviruses, in particular, the human immunodeficiency virus (HIV).
My laboratory is interested in developing improved oncoretroviral and lentiviral vectors, preclinical models for HIV/AIDS therapy and novel immuno-therapeutic strategies for cancer.
Over the past several years, we have studied molecular mechanisms of gene functions and pathogenesis of HIV, and developed novel oncoretro- and lentiviral vectors for therapeutic gene transfer. Together, with an improved suppressive subtractive hybridization cDNA cloning technique and novel small interfering RNA (siRNA) technology, we are exploring novel cancer genes and characterizing their functional pathways.
Other research topics include characterization of cellular and immune modulatory factors that are essential to the development of protective immunity to HIV and cancer. We have established reagents and protocols for oncoretro- and lentiviral gene transfer, siRNA delivery, vector titration and expression cell cloning. Further improvement on safety and scale-up production of gene transfer vectors is underway.
The goal of my research is to translate basic scientific discovery into clinical applications. For example, the project of combination immunogene therapy for cancer has been applied to a phase I clinical trial for brain and skin cancer treatment.
Specific:
Retroviruses are RNA viruses that synthesize DNA from the viral RNA genome and then integrate into the host cell genome by a process called reverse transcription and integration. My research has been focused on the study of gene regulation of retroviruses, in particular, the human immunodeficiency virus (HIV).
My laboratory is interested in developing improved oncoretroviral and lentiviral vectors, preclinical models for HIV/AIDS therapy and novel immuno-therapeutic strategies for cancer.
Over the past several years, we have studied molecular mechanisms of gene functions and pathogenesis of HIV, and developed novel oncoretro- and lentiviral vectors for therapeutic gene transfer. Together, with an improved suppressive subtractive hybridization cDNA cloning technique and novel small interfering RNA (siRNA) technology, we are exploring novel cancer genes and characterizing their functional pathways.
Other research topics include characterization of cellular and immune modulatory factors that are essential to the development of protective immunity to HIV and cancer. We have established reagents and protocols for oncoretro- and lentiviral gene transfer, siRNA delivery, vector titration and expression cell cloning. Further improvement on safety and scale-up production of gene transfer vectors is underway.
The goal of my research is to translate basic scientific discovery into clinical applications. For example, the project of combination immunogene therapy for cancer has been applied to a phase I clinical trial for brain and skin cancer treatment.
Other Expertise
1997-98, NIH, Special Review Committee, Pilot Studies on Gene Therapy Vectors for Metabolic Diseases Exploratory Grant Applications, NIDDK/NIH
1999-2001, Department of Defense, US Army, Breast Cancer Research Program, Member of Genetics Review Panel
2001-present, Associate Editor - Current Gene Therapy.
2002-2009, Expert and Consultant, International Atomic Energy Agency, United Nation
2003, NIH, Special Review Panel, Primate Core Laboratory
2004, NIH, Special Emphasis Panel, HIV Vaccine Research and Development
1999-2001, Department of Defense, US Army, Breast Cancer Research Program, Member of Genetics Review Panel
2001-present, Associate Editor - Current Gene Therapy.
2002-2009, Expert and Consultant, International Atomic Energy Agency, United Nation
2003, NIH, Special Review Panel, Primate Core Laboratory
2004, NIH, Special Emphasis Panel, HIV Vaccine Research and Development
Future Research
Development of lentiviral vectors, HIV therapy strategies, and cancer immunotherapy
Industrial Relevance
Discovery functional genomics
Gene therapy vectors
HIV and cancer therapeutics
Stem cells
Gene therapy vectors
HIV and cancer therapeutics
Stem cells
Keywords
COS Keywords:
AIDS, Blood Diseases, Brain Tumors, Cancer or Carcinogenesis, Gene Regulation, Gene Therapy, Gene Transfer, Genetic Diseases, HIV, Immune System Disorders, Immunotherapy, Microbiology, Molecular Genetics, Retrovirus, Stem Cells, Tumor Immunology, Tumors, Vaccine, Viral Infections.Additional Terms:
Cancer, HIV, Immunotherapy, Lentiviral Vectors, Vaccine.Languages
(Reading, Writing, Speaking)
Chinese, Mandarin: (Fluent, Fluent, Fluent)
English: (Fluent, Fluent, Fluent)
Memberships
American Association for Cancer Research
American Association for the Advancement of Science
American Society of Gene Therapy
American Society of Hematology
European Society of Gene and Cell Therapy
Honors and Awards
2004-2005,
Senior Research Scholar,
Multiple Myeloma Research Foundation
1997-1999,
Markey Scholar,
Lucille P. Markey Charitable Trust
1994-1995,
AHFMR Technology Commercialization Phase I Award,
AHFMR,
University of Alberta
1993-1997,
Research Scholar and Senior Scholar,
Alberta Heritage Foundation for Medical Research
1989-1993,
Fogarty International Visiting Associate,
NIAID,
National Institutes of Health
1986-1989,
Postdoctoral Fellowship,
Department of Microbiology,
University of California, San Francisco
1982-1986,
Teaching Assistantship,
Department of Microbiology,
University of Iowa
1981, Commissioned Officer Award,
Army,
Taiwan, ROC
1979, Matsumoto Scholar,
Department of Plant Pathology and Entomology,
National Taiwan University
1978-1980,
Book Coupon Award,
National Taiwan University,
Top 5% Scholar
1977-1980,
Tuition Award,
NTU,
National Taiwan University
Previous Positions
1993-1997, Assistant and Associate Professor,
University of Alberta,
Medicine and Dentistry,
Medicine
1989-1993, Visiting Associate,
National Institute of Health (NIH),
NIAID,
Laboratory of Molecular Microbiology
1986-1989, Postdoctorate,
University of California, San Francisco,
College of Medicine,
Microbiology
Patents
Production of mature and functional CD4 T cells developed from adult stem cells,
Patent Number: PCT/US2009/056739,
2008,
Institution,
United States of America.
Engineered dendritic cells for gene therapy,
Patent Number: ,
2007,
Institution,
United States of America.
Materials and methods for control of infections,
Patent Number: PCT/US/2007/011519,
2007,
Institution,
United States of America.
Combination Immunogene Therapy,
Patent Number: 6730512,
2004.
Long term expression of lentiviral vectors,
Patent Number: S/No. 60/385986,
2003.
Small interference RNA gene therapy,
Patent Number: PCT filed,
2003.
Lentiviral Vectors,
Patent Number: 6531123,
2003,
,
United States of America.
Modulation of dendritic cell function,
Patent Number: PCT 7655 1WO,
2002.
Lentiviral Vectors,
Patent Number: 6207455,
2001.
Method of using mouse model for evaluation of HIV vaccines,
Patent Number: 6248721,
2001,
,
United States of America.
Recombinant Hepatitis Virus Vectors,
Patent Number: 5981274,
1999.
Retroviral Expression Vectors Containing MoMLV/CMV-IE/HIV-TAR Chimeric Long Terminal Repeats,
Patent Number: 5693508,
1997.
Animal model for evaluation of vaccines,
Patent Number: ,
1997.
Funding Received
- NIHLB, NIH: Development of a recombinant lentiviral vector system, 1997 to 2007.
- NIAID, NIH: Hu-PBL-SCID/beige mouse model for HIV Vaccine Immunity Study, 1997 to 2000.
- Alberta Cancer Board: Anti-tumor immunogene therapy, to .
- NHRDP, MRC: Development of retroviral delivery system for anti-HIV gene theapy, to .
- MRC: Characterization of human host factors necessary for HIV attachment and penetration factors, to .
Publications
- Han, S., Liang, Y., Yang, F., Fu, Y., Wang, Y., Huang, Y., Lien, L., Chang, L.-J. (2009) Phenotype and functional analyses of therapeutic immune cells generated through interferon-gamma or CD137 selection versus dendritic cell activation approaches., Journal of Hematology and Oncoloby, 2, 34
- Patel, E., Wang, B., Lien, L., Wang, Y., Yang, L.-J., Moreb, J. S.., Chang, L.-J. (2009) Diverse T cell differentiation potentials of human fetal thymus, fetal liver, cord blood and adult bone marrow CD34 cells on lentiviral Delta-like 1-modified mouse stromal cells., Immunology, 128, e497-e505
- Wang, B., Han, S., Lien, L., Guo, L., Chang, L.-J. (2009) Lentiviral calnexin-modified dendritic cells promote expansion of high-avidity effector T cells with central memory phenotype, Immunology, 128, 43-57
- Han, S., Wang, B., Yang, L.-J., Zucali, J. R., Moreb, J. S., Chang, L.-J. (2008) Overcoming immune tolerance against multiple myeloma with lentiviral calnexin-engineered dendritic cells., Molecular Therapy, 16, 269-279
- Qing, Y., Lucas, L., Son, S., Chang, L.-J. (2007) Overlapping enhancer/promoter and transcriptional termination signals in the lentiviral long terminal repeat., Retrovirology, 4, 4
- Wang, B., He, J., Chen, L., Chang, L.-J. (2006) An effective cancer vaccine modality: lentiviral modification of dendritic cells expressing multiple cancer-specific antigens., Vaccine, 24, 3477-3489
- Wang, B, He, J., Chen, L. and Chang, L.-J., An effective cancer vaccine modality: lentiviral modification of dendritic cells expressing multiple cancer-specific antigens, Vaccine, In Press, 2006
- Parney, I. F., Chang, L.-J., Farr-Jones, M. A., Hao, C., Smylie, M., Petruk, K. C. (2006) Technical hurdles in a pilot clinical trial of combined B7-2 and GM-CSF immunogene therapy for glioblastomas and melanomas, Neurooncology, In Press
- Oka, M., Rodic, N., Graddy, J., Chang, L.-J. and Terada, N. (2006) CpG sites preferentially methylated by Dnmt3a in vivo, J. Biol. Chem., In Press
- Tang, D.-Q, Lu, S., Sun, Y.-P., Rodrigues, E., Chou, W., Yang, C., Cao, L.-Z., Chang, L.-J. and Yang, L.-J. (2006) Reprogramming liver-stem WB cells into functional insulin-producing cells by persistent expression of Pdx1- and Pdx1-VP16 mediated by lentiviral vectors, Laboratory Investigation, 86, 83-93
- He J, Yang Q, Chang LJ (Nov 2005) Dynamic DNA methylation and histone modifications contribute to lentiviral, Journal of Virology, 79 (21), 13497-508
- Lin G, Hayashi N, Carrion R, Chang LJ, Lue TF, Lin CS (Sep 2005) Improving erectile function by silencing phosphodiesterase-5, Journal of Urology, 174 (3), 1142-8
- Xiong C, Tang DQ, Xie CQ, Zhang L, Xu KF, Thompson WE, Chou W, Gibbons GH, Chang LJ, Yang LJ, Chen YE (Aug 2005) Genetic engineering of human embryonic stem cells with lentiviral vectors, Stem Cells and Development, 14 (4), 367-77
- Chang LJ, Liu X, He J (Jul 2005) Lentiviral siRNAs targeting multiple highly conserved RNA sequences of, Gene Therapy, 12 (14), 1133-44
- Chen, X. and Chang, L.-J. (2005) Mycoplasma-mediated Alterations of Functions and T Cell Immunity of Cultured Human Dendritic Cells, Journal of Biomedical Science, 12 (14), 31-46
- Chen X, He J, Chang LJ (Nov 2004) Alteration of T cell immunity by lentiviral transduction of human, Retrovirology, 1 (1), 37
- He J, Chang LJ (Jun 2004) Functional characterization of hepatoma-specific stem cell antigen-2, Molecular Carcinogenesis, 40 (2), 90-103
- Chang, L.-J., Vector integration: pest not guest, Gene Therapy, 10, 193-194, 2003
- Cui, Y. and Chang L.-J. (2003) Detection and selection of lentiviral vector transduced cells, Methods in Molecular Biology - Lentivirus Gene Engineering Protocols, 69-85 pages (bookchapter)
- Zaiss AK, Son S, Chang LJ (Jul 2002) RNA 3' readthrough of oncoretrovirus and lentivirus: implications for, Journal of Virology, 76 (14), 7209-19
- Chang LJ, Gay EE (Sep 2001) The molecular genetics of lentiviral vectors--current and future, Current Gene Therapy, 1 (3), 237-51
- Higashikawa, F. and Chang, L.-J., Kinetic analyses of simple and complex retroviral vectors, Virology, 280, 124-131, Jan 2001
- Chang, L.-J. and Gay, E. E., The molecular genetics of lentiviral vectors - current and future perspectives, Current Gene Therapy, 1, 237-251, 2001
- Chang, L.-J. and Zaiss, A.-K., Methods for the preparation and use of lentivirus vectors, Method in Molecular Medicine, Gene Therapy Protocol, Humana Press Inc., 303-318, 2001
- Chang, L.-J. and Jin, H., Retroviral vectors for gene therapy of AIDS and cancer, Current Opinion in Molecular Therapeutics, 3, 468-475, 2001
- Chang, L.-J. and Zaiss, A.-K. (2002) Self-inactivating lentiviral vectors in combination with a sensitive Cre-loxP reporter system, , Humana Press, Inc,, 367-382 pages (bookchapter)
- Parney IF, Farr-Jones MA, Chang LJ, Petruk KC, Human glioma immunobiology in vitro: implications for immunogene therapy, Neurosurgery, 46(5), 1169-77, May 2000
- Chang, L.-J., Chen, CH., Urlacher, V., Lee, TF. (2000) Differential apoptosis effects of primate lentiviral Vpr and Vpx in mammalian cells, Journal of Biomedical Science, 7 (4), 277-338
- Iwakuma T, Cui Y, Chang LJ, Self-inactivating lentiviral vectors with U3 and U5 modifications, Virology, 261(1), 120-32, August 1999
- Cui Y, Iwakuma T, Chang LJ (July 1999) Contributions of viral splice sites and cis-regulatory elements to lentivirus vector function, Journal of Virology, 73 (7), 6171-6
- Chang, L.-J., V. Urlacher, T. Iwakuma, Y. Cui and J. Zucali, Efficacy and safety analyses of a recombinant human immunodeficiency virus derived vector system, Gene Therapy, 6, 715-728, 1999
- Cui, Y. and Chang, L.-J., A rapid and reliable bioassay for functional human interleukin-12 by interferon-g ELISPOT, Preparative Biochemistry and Biotechnology, 28, 23-36, 1998
- Chaisomchit S, Tyrrell DL, Chang LJ, Development of replicative and nonreplicative hepatitis B virus vectors, Gene Therapy, 4(12), 1330-40, December 1997
- Kilani RT, Chang LJ, Garcia-Lloret MI, Hemmings D, Winkler-Lowen B, Guilbert LJ (September 1997) Placental trophoblasts resist infection by multiple human immunodeficiency virus (HIV) type 1 variants even with cytomegalovirus coinfection but support HIV replication after provirus transfection, Journal of Virology, 71 (9), 6359-72
- Cui Y, Chang LJ, Computer-assisted, quantitative cytokine enzyme-linked immunospot analysis of human immune effector cell function, Biotechniques, 22(6), 1146-9, June 1997
- Parney IF, Petruk KC, Zhang C, Farr-Jones M, Sykes DB, Chang LJ, Granulocyte-macrophage colony-stimulating factor and B7-2 combination immunogene therapy in an allogeneic Hu-PBL-SCID/beige mouse-human glioblastoma multiforme model, Human Gene Therapy, 8(9), 1073-85, June 1997
- Zhang C, Rasmussen C, Chang LJ, Cell cycle inhibitory effects of HIV and SIV Vpr and Vpx in the yeast Schizosaccharomyces pombe, Virology, 230(1), 103-12, March 1997
- Zhang C, Cui Y, Houston S, Chang LJ, Protective immunity to HIV-1 in SCID/beige mice reconstituted with peripheral blood lymphocytes of exposed but uninfected individuals, Proceedings of the National Academy of Sciences (USA), 93(25), 14720-5, December 1996
- Robinson D, Elliott JF, Chang LJ, Retroviral vector with a CMV-IE/HIV-TAR hybrid LTR gives high basal expression levels and is up-regulated by HIV-1 Tat, Gene Therapy, 2(4), 269-78, June 1995
- Chang LJ, McNulty E, Martin M (February 1993) Human immunodeficiency viruses containing heterologous enhancer/promoters are replication competent and exhibit different lymphocyte tropisms, Journal of Virology, 67 (2), 743-52
- Chang LJ, Hirsch RC, Ganem D, Varmus HE (November 1990) Effects of insertional and point mutations on the functions of the duck hepatitis B virus polymerase, Journal of Virology, 64 (11), 5553-8
- Chang LJ, Ganem D, Varmus HE, Mechanism of translation of the hepadnaviral polymerase (P) gene, Proceedings of the National Academy of Sciences (USA), 87(13), 5158-62, July 1990
- Hirsch RC, Lavine JE, Chang LJ, Varmus HE, Ganem D, Polymerase gene products of hepatitis B viruses are required for genomic RNA packaging as wel as for reverse transcription, Nature, 344(6266), 552-5, April 1990
- Chang LJ, Pryciak P, Ganem D, Varmus HE, Biosynthesis of the reverse transcriptase of hepatitis B viruses involves de novo translational initiation not ribosomal frameshifting, Nature, 337(6205), 364-8, January 1989
- Chang LJ, Stoltzfus CM (March 1987) Inhibition of Rous sarcoma virus replication by antisense RNA, Journal of Virology, 61 (3), 921-4
- Chang LJ, Stoltzfus CM, Gene expression from both intronless and intron-containing Rous sarcoma virus clones is specifically inhibited by anti-sense RNA, Molecular and Cellular Biology, 5(9), 2341-8, September 1985
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COS Expertise ID #423593
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