Tobias Hahn |
|
Providence Portland Medical Center Robert W. Franz Cancer Research Center Earle A. Chiles Research Institute Laboratory of Tumor Immunology and Therapeutics Research ScientistAppointed: 2008 |
Mailing AddressLaboratory of Tumor Immunology and Therapeutics Providence Portland Medical Center Earle A. Chiles Research Institute 4805 NE Glisan St Portland, Oregon 97213United States | Contact Information |
Qualifications
Ph.D., University of Arizona, Microbiology and Immunology, 2002.
Expertise and Research Interests
Tumor Immunology and Cancer Vaccine Development:
The major goal of our laboratory is to elucidate the role played by tumor cells in suppressing antitumor responses and to design therapeutic strategies to restore the antigen-presenting functions of dendritic cells as well as the effector function of tumor-specific T lymphocytes.
Our efforts have focused on the use of dendritic cells (DC) as a vaccine for the treatment of cancer. The ability of DC to stimulate naive T lymphocytes and boost memory immune responses has made them prime candidates for cancer immunotherapy. Although numerous studies in animal models have documented the ability of DC-based vaccines to prevent tumor growth, there has been limited success of treating established disease with DCs. This is in part due to the ability of tumors to evade the immune system by secreting factors that inhibit an effective immune response.
To make DC vaccines more effective it is essential to overcome the tumor-induced immunosuppression and to make tumor antigens available to effector T-cells. Therefore, the strategies we are implementing in the lab are to a) neutralize or eliminate tumor-generated immunosuppressive products; b) kill tumor cells in situ to provide tumor antigens to DC using chemotherapeutic agents; c) stimulate a sufficient immune memory to establish long-lasting protection.
Role of TGF-ß in Tumor Immunology:
One of the major projects in the lab is aimed at neutralizing the effects of transforming growth factor beta (TGF-ß), an immunosuppressive cytokine that is secreted by many tumor types in large quantities. To achieve this we are employing a TGF-ß receptor kinase inhibitor to block TGF-ß signaling. We have found that this small molecule inhibitor effectively prevents TGF-ß initiated signaling events in vitro and slows tumor progression in combination with DC vaccination in mouse models in vivo.
Chemo-Immunotherapy of Cancer:
We are also developing a chemo-immunotherapy strategy that combines DC vaccination with the novel chemotherapeutic agent alpha-tocopheryl succinate (alpha-TOS). alpha-TOS is an esterified analog of vitamin E and kills tumors cells while minimally affecting normal cells. We have seen that systemic administration of alpha-TOS in combination with DC vaccination significantly inhibits tumor growth in mouse models.
Peptide Specific Immunotherapy of Colon Cancer:
In addition, we are investigating strategies to induce an anti-cancer immune memory using peptide vaccinations to achieve long-term immune protection. Using a transgenic mouse model, we have found that peptide vaccination decreases the number and size of polyps, which are precursors of invasive colon cancer.
We hope to develop new approaches of cancer treatment that can be easily adopted for treating cancers in humans as well as improve our understanding of the immunologic mechanisms of tumor immunity.
The major goal of our laboratory is to elucidate the role played by tumor cells in suppressing antitumor responses and to design therapeutic strategies to restore the antigen-presenting functions of dendritic cells as well as the effector function of tumor-specific T lymphocytes.
Our efforts have focused on the use of dendritic cells (DC) as a vaccine for the treatment of cancer. The ability of DC to stimulate naive T lymphocytes and boost memory immune responses has made them prime candidates for cancer immunotherapy. Although numerous studies in animal models have documented the ability of DC-based vaccines to prevent tumor growth, there has been limited success of treating established disease with DCs. This is in part due to the ability of tumors to evade the immune system by secreting factors that inhibit an effective immune response.
To make DC vaccines more effective it is essential to overcome the tumor-induced immunosuppression and to make tumor antigens available to effector T-cells. Therefore, the strategies we are implementing in the lab are to a) neutralize or eliminate tumor-generated immunosuppressive products; b) kill tumor cells in situ to provide tumor antigens to DC using chemotherapeutic agents; c) stimulate a sufficient immune memory to establish long-lasting protection.
Role of TGF-ß in Tumor Immunology:
One of the major projects in the lab is aimed at neutralizing the effects of transforming growth factor beta (TGF-ß), an immunosuppressive cytokine that is secreted by many tumor types in large quantities. To achieve this we are employing a TGF-ß receptor kinase inhibitor to block TGF-ß signaling. We have found that this small molecule inhibitor effectively prevents TGF-ß initiated signaling events in vitro and slows tumor progression in combination with DC vaccination in mouse models in vivo.
Chemo-Immunotherapy of Cancer:
We are also developing a chemo-immunotherapy strategy that combines DC vaccination with the novel chemotherapeutic agent alpha-tocopheryl succinate (alpha-TOS). alpha-TOS is an esterified analog of vitamin E and kills tumors cells while minimally affecting normal cells. We have seen that systemic administration of alpha-TOS in combination with DC vaccination significantly inhibits tumor growth in mouse models.
Peptide Specific Immunotherapy of Colon Cancer:
In addition, we are investigating strategies to induce an anti-cancer immune memory using peptide vaccinations to achieve long-term immune protection. Using a transgenic mouse model, we have found that peptide vaccination decreases the number and size of polyps, which are precursors of invasive colon cancer.
We hope to develop new approaches of cancer treatment that can be easily adopted for treating cancers in humans as well as improve our understanding of the immunologic mechanisms of tumor immunity.
Other Expertise
Previous Research:
Vertical Transmission of HIV-1 occurs at an estimated rate of 15-30% and accounts for 90% of all HIV-1 infections in children. Since approximately 40% of new cases of HIV-1 infection are among women of the childbearing age group, an increased number of children are in danger to be born HIV-1 positive. The molecular mechanisms of vertical transmission are poorly understood, therefore, characterization of HIV-1 associated with mother-infant transmission canprovide relevant information toward the development of effective and new strategies for prevention and treatment of vertical transmission of HIV-1.
Our hypothesis is that specific molecular and biological properties of HIV-1 are critical determinants of vertical transmission. Analyzing the env-gene, we and others have shown that HIV-1 minor genotypes with macrophage-tropic and non-syncytium inducing phenotypes (R5 virus) were transmitted from mothers to infants. Selective transmission of the minor subtype with a R5 phenotype, has also been shown during sexual and parenteral transmission of HIV-1. We characterized the HIV-1 gag p17 matrix (MA) and nef genes associated with and without vertical transmission. In addition, we determined the effect of env gp120 from mother-infant pairs and from infected mothers who failed to transmit the virus to their infants (non-transmitting mothers) on HIV-1 replication, cellular tropism, cytopathic effects and co-receptor utilization.
Vertical Transmission of HIV-1 occurs at an estimated rate of 15-30% and accounts for 90% of all HIV-1 infections in children. Since approximately 40% of new cases of HIV-1 infection are among women of the childbearing age group, an increased number of children are in danger to be born HIV-1 positive. The molecular mechanisms of vertical transmission are poorly understood, therefore, characterization of HIV-1 associated with mother-infant transmission canprovide relevant information toward the development of effective and new strategies for prevention and treatment of vertical transmission of HIV-1.
Our hypothesis is that specific molecular and biological properties of HIV-1 are critical determinants of vertical transmission. Analyzing the env-gene, we and others have shown that HIV-1 minor genotypes with macrophage-tropic and non-syncytium inducing phenotypes (R5 virus) were transmitted from mothers to infants. Selective transmission of the minor subtype with a R5 phenotype, has also been shown during sexual and parenteral transmission of HIV-1. We characterized the HIV-1 gag p17 matrix (MA) and nef genes associated with and without vertical transmission. In addition, we determined the effect of env gp120 from mother-infant pairs and from infected mothers who failed to transmit the virus to their infants (non-transmitting mothers) on HIV-1 replication, cellular tropism, cytopathic effects and co-receptor utilization.
Keywords
COS Keywords:
Cancer or Carcinogenesis, Immunology, Immunotherapy, Microbiology, Tumor Immunology.Additional Terms:
Cancer Immunology, Immunology, Immunotherapy.Languages
(Reading, Writing, Speaking)
English: (Fluent, Fluent, Fluent)
German: (Fluent, Fluent, Fluent)
Memberships
American Association for the Advancement of Science
Previous Positions
2008-2008, Research Assistant Professor,
University of Arizona,
Arizona Health Sciences Center,
Immunobiology
2002-2008, Research Associate,
University of Arizona,
Arizona Health Sciences Center,
Immunobiology
1997-2002, Research Assistant,
University of Arizona,
Arizona Health Sciences Center,
Microbiology and Immunology
Publications
- Akporiaye ET, Bradley-Dunlop D, Gendler SJ, Mukherjee P, Madsen CS, Hahn T, Besselsen DG, Dial SM, Cui H, Trevor K (2007) Characterization of the MUC1.Tg/MIN transgenic mouse as a model for studying antigen-specific immunotherapy of adenomas, Vaccine, 25 (39-40), 6965-74
- Neuzil J, Dong L-F, Ramanathapuram L, Hahn T, Chaldova M, Wang X-F, Zobalova R, Prochazka L, Gold M, Freeman R, Turanek J, Akporiaye ET, Dayson JC, Ralph SJ (2007) Vitamin E analogues as a novel group of mitocans: Anti-cancer agents that act by targeting mitochondria, Molecular Aspects of Medicine
- Tobias Hahn, Lajos Szabo, Mikhal Gold, Lalitha Ramanathapuram, Laurence H. Hurley, Emmanuel T. Akporiaye (2006) Dietary administration of the pro-apoptotic Vitamin E analog alpha-tocopheryloxyacetic acid inhibits metastatic murine breast cancer, Cancer Research, 66 (18), 9374-9378
- Tobias Hahn, Emmanuel T. Akporiaye, Targeting transforming growth factor beta to enhance cancer immunotherapy, Curr Oncology, 13(4), 141-43, 2006
- Tobias Hahn, Irene Alvarez, James Kobie, Lalitha Ramanathapuram, Sharon Dial, Amy Fulton, David Besselsen, Edwin Walker, Emmanuel Akporiaye (2006) Short-term Dietary Administration of Celecoxib Enhances the Efficacy of Tumor Lysate-pulsed Dendritic Cell Vaccines in Treating Murine Breast Cancer, Int. Journal of Cancer, 118 (2), 2220-2231
- Ramanathapuram, L., Hahn, T., Dial, S., Akporiaye, E. T. (2005) Chemo-Immunotherapy of Breast Cancer Using Vesiculated Alpha-Tocopheryl Succinate in Combination, Nutrition and Cancer, 53 (2), 177-193
- Ramanathapuram L.V., Hahn, T., Graner M.W., Katsanis E., Akporiaye E.T. (2006) Vesiculated Alpha-tocopheryl Succinate Enhances the Anti-tumor Effect of Dendritic Cell Vaccines, Cancer Immunol Immunother, 55 (2), 166-177
- Sundaravaradan, V., Hahn, T., Ahmad, N., Conservation of Functional Domains and Limited Heterogeneity of HIV-1 Reverse Transcritpase Gene Following Vertical Transmission, Retrovirology, 2(1), 36, 26 May 2005
- Hahn T, Ramakrishnan R, Ahmad N, Evaluation of Genetic Diversity of Human Immunodeficiency Virus Type 1 NEF
Gene Associated with Vertical Transmission, Journal of Biomedical Science, 10(4), 436-50, 2003
- Matala E, Hahn T, Yedavalli VR, Ahmad N, Biological characterization of HIV type 1 envelope V3 regions from mothers
and infants associated with perinatal transmission, Aids Research and Human Retroviruses, 17(18), 1725-35, December 2001
- Hahn T, Ahmad N, Genetic characterization of HIV type 1 gag p17 matrix genes in isolates
from infected mothers lacking perinatal transmission, Aids Research and Human Retroviruses, 17(17), 1673-80, November 2001
- Husain M, Hahn T, Yedavalli VR, Ahmad N, Characterization of HIV type 1 tat sequences associated with perinatal
transmission, Aids Research and Human Retroviruses, 17(8), 765-73, May 2001
- Hahn T, Matala E, Chappey C, Ahmad N, Characterization of mother-infant HIV type 1 gag p17 sequences associated
with perinatal transmission, Aids Research and Human Retroviruses, 15(10), 875-88, July 1999
- Nafees Ahmad, Erik Matala, R. K. Venkat Yedavalli, Tobias Hahn (1998) Characterization of Human Immunodeficiency Virus Type-1 Involved in Maternal-Fetal Transmission, Advances in Animal Virology, New Delhi/Calcutta, Oxford and IBH Publishing Co. Ltd., 351-370 pages (bookchapter)
Profile Details
Last Updated: 9/16/2008
COS Expertise ID #1110230
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