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.
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 is director of the Laboratory of Neurovirology and Neuroimmunology. He investigates the role of the host immune response in the pathogenesis herpes simplex virus (HSV) infections in vivo, with particular emphasis on CNS infections and the regulation of latency. His laboratory is also investigating the mechanisms by which intravenous immunoglobulins (IVIG) act as a potent immunomodulatory drug to suppress virus induced hyper-inflammatory responses that in the CNS culminate in fatal encephalitis following infection with HSV or West Nile virus, or fatal pneumonia following infection with highly pathogenic influenza virus strains, such as pandemic H1N1. A long-term interest is to understand the genetic basis of innate resistance to HSV, as this may suggest rational approaches to controlling recurrent infections, and the development of serious diseases such as encephalitis.
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.

Don J. Diamond, Ph.D. – Vaccine Research
Don Diamond, Ph.D., associate chair and 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.

Jiing-Kuan Yee, Ph.D.Modeling human diseases with stem cells
Dr. Yee is interested in using cell reprogramming and gene editing to establish ex vivo human genetic disease models to explore the underlying disease mechanisms and develop therapeutic strategies for treatment.  He has established fibroblast-derived induced pluripotent stem cells (iPSCs) from spinal muscular atrophy and Wiskott-Aldrich syndrome patients.  He is studying the phenotypes of cells differentiated from these iPSC lines to understand the pathogenesis of the disease.  He is also using gene editing technology to modify the genome of the iPSCs to explore the possibility of treating these diseases with cell replacement therapy.
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.