©
2013 City of Hope
1500 East Duarte Road
Duarte, CA 91010
626-256-HOPE (4673)
1500 East Duarte Road
Duarte, CA 91010
626-256-HOPE (4673)
A National Cancer Institute-designated Comprehensive Cancer Center
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Virology
Virology
City of Hope’s Department of Virology strives to better understand the origin and development of herpes simplex virus and other herpes viruses, the biology of cytomegalovirus (a prime concern for HIV-infected and other immunocompromised patients such as transplant recipients), vaccine development and experimental therapies using gene transfer vectors such as adeno-associated virus (AAV) and lentivirus. Viral vectors have shown great promise in treating both cancers and HIV.
John A. Zaia, M.D., chair of the department, plays an integral role in the Hematopoietic Cell Transplantation Program’s efforts to understand the biology of cytomegalovirus (CMV)-related pneumonitis, which was a major limitation to the success of bone marrow transplantation, and later went on to develop the gene therapy program at City of Hope, focused on treatment of HIV with genetically modified stem cells and T cells.
The Department of Virology comprises more than 50 personnel, including professors, associate professors, support scientists, postdoctoral fellows, research associates, laboratory aides and administrative support.
John A. Zaia, M.D., chair of the department, plays an integral role in the Hematopoietic Cell Transplantation Program’s efforts to understand the biology of cytomegalovirus (CMV)-related pneumonitis, which was a major limitation to the success of bone marrow transplantation, and later went on to develop the gene therapy program at City of Hope, focused on treatment of HIV with genetically modified stem cells and T cells.
The Department of Virology comprises more than 50 personnel, including professors, associate professors, support scientists, postdoctoral fellows, research associates, laboratory aides and administrative support.
Laboratory Research
John Zaia, M.D.– Antiviral Research
Zaia, department chair, joined City of Hope from Harvard in 1980. He directs two clinical research labs, the Cytomegalovirus (CMV) Lab and the HIV Lab, with interests in antiviral development in the area of herpes viruses and HIV. The CMV laboratory studies the immunobiology of CMV infection after hematopoietic cell transplantation (HCT) with emphasis on immune factors necessary for protection. The HIV laboratory focuses on developing new treatments for HIV/AIDS using optimal genetic vectors for anti-HIV gene transfer and novel drug therapy.
Edouard Cantin, Ph.D.– Neurovirology and Neuroimmunology
Cantin, associate chair of the department, is director of the Laboratory of Neurovirology and Neuroimmunology. He investigates the role of cytokines/chemokines such as TNF (tumor necrosis factor) in herpes simplex virus (HSV) infections in vivo, with particular emphasis on latent infections. His laboratory is also interested in characterizing – on a genetic and molecular biological basis - determinants of natural resistance to HSV, with emphasis on the genetic explanation for sex-based differences in infection and the role of innate immunity in disease pathogenesis. Understanding mechanisms of latency and natural resistance in HSV may suggest rational approaches to controlling recurrent infections, and perhaps even devising a cure.
Saswati Chatterjee, Ph.D.– Gene Therapy
Chatterjee directs the Adeno-Associated Virus (AAV) Laboratory and is interested in the biology of AAV vectors for therapeutic gene transfer. Her specific areas of interest include stem cell-based genetic therapies of acquired and inherited diseases, including HIV infection, cancer, cardiovascular and genetic diseases; virus discovery research in human stem cells and the study of genetic elements necessary for optimal gene-based therapies. She evaluates gene therapy approaches in both in vitro and in vivo pre-clinical models, with targeted progression toward clinical human gene therapy trials.
Larry Couture, Ph.D.– Technology Development
Couture oversees the Center for Applied Technology Development, which includes the Center for Biomedicine and Genetics (CBG), directed by David Hsu, Ph.D., and the offices of IND Development & Regulatory Affairs, Quality Assurance and Technology Licensing. The CBG manufactures clinical-grade quality viral and non-viral vectors, recombinant proteins, bacterial products and cell-based products. The CBG staff is developing manufacturing processes for adenovirus, rAAV, lentivirus and plasmid DNA vectors for phase I and phase II clinical trials. Biologicals developed and produced by CBG translate into clinical trials at City of Hope and elsewhere, via our Production Partnership Program, which works with other academic institutions and biopharmaceutical companies.
Don J. Diamond, Ph.D.– Vaccine Research
Don Diamond, Ph.D., the Tim Nesvig Lymphoma Research Fellow at City of Hope, directs the Division of Translational Vaccine Research (TVR), which develops vaccines to combat hematologic malignancies, solid tumors, and infectious pathogens such as the herpesvirus, cytomegalovirus (CMV) and human immunodeficiency virus, or HIV. The prospect of an effective CMV vaccine means significant benefits for immunocompromised patients such as those with AIDS, or stem cell and solid organ transplant recipients. A therapeutic CMV peptide vaccine developed in the TVR is undergoing phase II human efficacy testing in City of Hope stem cell transplant recipients, while a second generation CMV vaccine based on the attenuated poxvirus MVA, or modified vaccinia Ankara, will initiate phase I human safety testing in fall 2013. A vaccine developed in the TVR also based on the MVA platform expressing unmutated p53 is undergoing phase I human testing in City of Hope gastrointestinal cancer patients. In the laboratory, we are refining a therapeutic platform based on attenuated Salmonella bacterium to treat a range of malignancies including pancreatic, skin and brain cancers. In collaboration with Peter Barry, Ph.D., of University of California at Davis and the National Primate Research Center, we are developing a prophylactic CMV vaccine that promises to control gestational infection that causes a wide range of birth defects that annually afflict close to 4,000 American children.
K.K. Wong, M.D.– Gene Therapy
Wong is a collaborator in the AAV Laboratory. His research interests include recombinant adeno-associated virus (rAAV) vector development, which is applied to producing tumor-specific vaccines and inhibiting viruses such as HSV, HPV and HIV. Other research includes transducing hematopoietic stem cells, and gene therapy with the Apo-A1 protein to treat atherosclerosis.
Jiing-Kuan Yee, Ph.D.– Human Gene Therapy
Yee is the director of the Lentivirus Laboratory. His specific interests include development of lentiviral vectors such as HIV and FIV to deliver transgenes into cells for potential treatment of human diseases such as hemophilia. He is also using these vectors to transduce anti-HIV genes into hematopoietic stem cells.
John Zaia, M.D.– Antiviral Research
Zaia, department chair, joined City of Hope from Harvard in 1980. He directs two clinical research labs, the Cytomegalovirus (CMV) Lab and the HIV Lab, with interests in antiviral development in the area of herpes viruses and HIV. The CMV laboratory studies the immunobiology of CMV infection after hematopoietic cell transplantation (HCT) with emphasis on immune factors necessary for protection. The HIV laboratory focuses on developing new treatments for HIV/AIDS using optimal genetic vectors for anti-HIV gene transfer and novel drug therapy.
Edouard Cantin, Ph.D.– Neurovirology and Neuroimmunology
Cantin, associate chair of the department, is director of the Laboratory of Neurovirology and Neuroimmunology. He investigates the role of cytokines/chemokines such as TNF (tumor necrosis factor) in herpes simplex virus (HSV) infections in vivo, with particular emphasis on latent infections. His laboratory is also interested in characterizing – on a genetic and molecular biological basis - determinants of natural resistance to HSV, with emphasis on the genetic explanation for sex-based differences in infection and the role of innate immunity in disease pathogenesis. Understanding mechanisms of latency and natural resistance in HSV may suggest rational approaches to controlling recurrent infections, and perhaps even devising a cure.
Saswati Chatterjee, Ph.D.– Gene Therapy
Chatterjee directs the Adeno-Associated Virus (AAV) Laboratory and is interested in the biology of AAV vectors for therapeutic gene transfer. Her specific areas of interest include stem cell-based genetic therapies of acquired and inherited diseases, including HIV infection, cancer, cardiovascular and genetic diseases; virus discovery research in human stem cells and the study of genetic elements necessary for optimal gene-based therapies. She evaluates gene therapy approaches in both in vitro and in vivo pre-clinical models, with targeted progression toward clinical human gene therapy trials.
Larry Couture, Ph.D.– Technology Development
Couture oversees the Center for Applied Technology Development, which includes the Center for Biomedicine and Genetics (CBG), directed by David Hsu, Ph.D., and the offices of IND Development & Regulatory Affairs, Quality Assurance and Technology Licensing. The CBG manufactures clinical-grade quality viral and non-viral vectors, recombinant proteins, bacterial products and cell-based products. The CBG staff is developing manufacturing processes for adenovirus, rAAV, lentivirus and plasmid DNA vectors for phase I and phase II clinical trials. Biologicals developed and produced by CBG translate into clinical trials at City of Hope and elsewhere, via our Production Partnership Program, which works with other academic institutions and biopharmaceutical companies.
Don J. Diamond, Ph.D.– Vaccine Research
Don Diamond, Ph.D., the Tim Nesvig Lymphoma Research Fellow at City of Hope, directs the Division of Translational Vaccine Research (TVR), which develops vaccines to combat hematologic malignancies, solid tumors, and infectious pathogens such as the herpesvirus, cytomegalovirus (CMV) and human immunodeficiency virus, or HIV. The prospect of an effective CMV vaccine means significant benefits for immunocompromised patients such as those with AIDS, or stem cell and solid organ transplant recipients. A therapeutic CMV peptide vaccine developed in the TVR is undergoing phase II human efficacy testing in City of Hope stem cell transplant recipients, while a second generation CMV vaccine based on the attenuated poxvirus MVA, or modified vaccinia Ankara, will initiate phase I human safety testing in fall 2013. A vaccine developed in the TVR also based on the MVA platform expressing unmutated p53 is undergoing phase I human testing in City of Hope gastrointestinal cancer patients. In the laboratory, we are refining a therapeutic platform based on attenuated Salmonella bacterium to treat a range of malignancies including pancreatic, skin and brain cancers. In collaboration with Peter Barry, Ph.D., of University of California at Davis and the National Primate Research Center, we are developing a prophylactic CMV vaccine that promises to control gestational infection that causes a wide range of birth defects that annually afflict close to 4,000 American children.
K.K. Wong, M.D.– Gene Therapy
Wong is a collaborator in the AAV Laboratory. His research interests include recombinant adeno-associated virus (rAAV) vector development, which is applied to producing tumor-specific vaccines and inhibiting viruses such as HSV, HPV and HIV. Other research includes transducing hematopoietic stem cells, and gene therapy with the Apo-A1 protein to treat atherosclerosis.
Jiing-Kuan Yee, Ph.D.– Human Gene Therapy
Yee is the director of the Lentivirus Laboratory. His specific interests include development of lentiviral vectors such as HIV and FIV to deliver transgenes into cells for potential treatment of human diseases such as hemophilia. He is also using these vectors to transduce anti-HIV genes into hematopoietic stem cells.
Division of Translational Vaccine Research
The LVR was formed to address priorities in vaccine research that will potentially impact patient outcomes at City of Hope and other cancer centers worldwide
The LVR was formed to address priorities in vaccine research that will potentially impact patient outcomes at City of Hope and other cancer centers worldwide
Virology Faculty
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Division of Translational Vaccine Research
The LVR was formed by Dr. Diamond in 2000 to address priorities in vaccine research that will potentially impact patient outcomes at City of Hope (COH) and other cancer centers worldwide. In 2008, Dr. Diamond formed the TVR to expand the work started in the LVR towards additional tumor types and to accelerate clinical development of promising vaccine strategies. The foundation of the research priorities of the program grew out of the extensive collaboration with the Hematopoietic Stem Cell Transplant Program at COH, and the need for an effective therapeutic strategy for infections post-transplant (Tx). The infection that has historically played a major role in reducing Tx success rate is the herpes virus called cytomegalovirus (CMV). In 1993 an immunologic approach was developed for controlling this virus, and this work has continued. The TVR has a two pronged attack on virus infection using two different but allied approaches for therapy. The first approach relies on a non-living synthetic portion of the virus called a peptide that has cleared its safety hurdle after a successful clinical trial in healthy volunteers. The peptide is now undergoing preliminary efficacy testing in stem cell transplant recipients at COH. The goal of this trial is to measure if it is immunologically recognized. In cooperation with physicians at the University of Minnesota, we are expanding the evaluation to cover all types of stem cell transplant including cord blood. The goal is to discover if it is protective against CMV infection and substitutes for toxic anti-viral drugs that hamper recovery. The 2nd approach is nearing submission to the FDA for review and permission to conduct a 1st in humans safety trial. While the peptide applies to about 40% of transplant recipients, the newer approach would be universal in coverage. It is designed to protect both stem cell and solid organ transplant recipients. We anticipate the 1st safety trial to begin in late 2013.
Based on work initiated 2 decades ago with former COH surgical oncologist and clinical researcher, Dr. Joshua D.I. Ellenhorn, a Phase 1 safety trial of a cancer vaccine was started in early 2012. Gastro-intestinal patients with inoperable disease are receiving the vaccine, and TVR personnel are monitoring its immunologic recognition, while Dr. Vincent Chung, a COH medical oncologist is assessing clinical responses based on CT-scans. Using a different vector system based on an attenuated Salmonella strain, TVR investigators have developed a therapeutic strategy that applies to a large panel of solid tumors and melanoma. The strategy depends on using RNAi to deplete immunosuppressive molecules to allow anti-tumor immunity to flourish. We are also trying to adopt this therapy to brain cancer, where immunosuppression is strong and standard approaches have largely failed.
Continuing the theme of brain injury, we are pursuing a vaccine strategy to prevent birth defects that strongly impact lifelong cognitive abilities. Interestingly, the culprit is still CMV, but in this case it infects women of child-bearing years who were never previously exposed, and causes harm to over 4000 neonates annually in the USA. We are in the process of developing a more effective vaccine than one already investigated and found only to be 50% effective at controlling CMV infection in neonates.
We welcome inquiries about our ongoing programs which can be found as a sidebar together with the TVR investigators and outside collaborators who are leading the research effort.
Beckman Research Institute
i
Recognized nationwide for its innovative biomedical research, Beckman Research Institute of City of Hope is home to some of the most creative minds in science.
Research at City of Hope
Research pioneered at City of Hope and its
renowned Beckman Research Institute has
improved the lives of men, women and children throughout the world.
Beckman Research Institute boasts a wide array of technological and academic resources that are critical to effective research. These shared resources include diverse laboratory services, access to state-of-the-art equipment and expert administrative guidance.
City of Hope’s Irell & Manella Graduate School of Biological Sciences equips students with the skills and strategies to transform the future of modern medicine.
Develop new therapies, diagnostics and preventions in the fight against cancer and other life-threatening diseases.
Laboratories/Research Projects
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