Research Abstract

My research interests are in the field of human antibody engineering and the use of human antibodies in discovery research and in the treatment of human diseases. I am a physician/scientist with clinical training in Infectious Diseases. My clinical subspecialty training is in the care of immunocompromised patients with bone marrow and solid organ transplants and cancer. My clinical practice has had a profound influence on the research conducted in my laboratory at Dana-Farber Cancer Institute. During my rotations on the inpatient Infectious Disease service at BWH/DFCI, I supervise ID fellows and medical residents in the management of infections in immunocompromised patients. As a principal investigator, I supervise two junior faculty, seven post-doctoral fellows/scholars and five research technicians. This supervision involves mentorship roles in bench and clinical research, manuscript review and grant writing. On the national level, I am a member of the AIDS Immunopathogenesis study section and have a leadership role in the organization of and presentation at targeted gene therapy and antibody engineering meetings.

My laboratory is working in the areas of HIV/AIDS, emerging infectious diseases (SARS, highly pathogenic H5N1 avian influenza (bird flu), West Nile Virus (encephalitis), Denge virus (hemorrhagic fever)) and cancer (Adult T-cell Leukemia (HTLV-1), breast CA, renal cell carcinoma (RCC), cutaneous T-cell Lymphoma (CTCL)). This breadth of research is made possible because of two research developments in my laboratory in the field of human antibody engineering. The first is our seminal discovery that human antibodies can not only be used to target proteins on the surface of cells and microbes but can also be used in the form known as intracellular antibodies or intrabodies, which can be delivered to cells by gene transfer techniques. In this way, human antibodies can be expressed in different subcellular compartments inside cells where they can bind to their target protein and modulate its function. The second research development in my laboratory is the construction and characterization of one of the largest human antibody phage display libraries ever made (27 billion members). We have validated the quantity and high quality of the human antibodies that can be obtained from this library through the discoveries that we have made in the research areas mentioned above. Ongoing pre-clinical studies and clinical trials using human monoclonal antibodies (Mabs) are moving forward for the prevention and treatment of SARS and flavivirus diseases including West Nile virus encephalitis. We are also moving forward with a genetic/cellular therapy for the treatment of RCC.

In an effort to greatly expand the use of human monoclonal antibodies (Mab) in the treatment of cancer, I founded the National Foundation of Cancer Research (NFCR) Center for Therapeutic Antibody Engineering (CTAE) (http://www.nfcr-ctae.org/). My CTAE laboratory at Dana-Farber Cancer Institute is working with cancer investigators around the globe to utilize our human antibody library to discover new human Mab for the treatment of cancer. In this way, the CTAE can facilitate a broad range of discovery and translational research in cancer that would not be possible for a single laboratory. This also allows CTAE to work with some of the most accomplished cancer investigators in the world.