Diana V. Pastrana, Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Buildng 37, Room 4118
- Bethesda, MD 20892
- 240-760-7923
- 240-541-4502
- pastrand@mail.nih.gov
RESEARCH SUMMARY
Dr. Pastrana's projects in the LCO have explored protective antibody responses against small DNA tumor viruses, a group that includes papillomaviruses and polyomaviruses. She has developed tests to determine the virus-neutralizing potency of antibody responses elicited by vaccines. Her findings in this area led to the development and licensing of polyomavirus vaccine technologies. A vaccine against BK and JC polyomaviruses is currently progressing toward clinical trials that will examine its utility for preventing polyomavirus-induced kidney damage in organ transplant recipients. Dr. Pastrana has also led virus-discovery efforts uncovering dozens of previously unknown DNA tumor viruses and other previously unknown viruses. Her other contributions to the field include findings that have elucidated host/pathogen interactions and characterization of the receptors different polyomavirus strains use to infect cells.
Areas of Expertise
Diana V. Pastrana, Ph.D.
Publications
Host-Pathogen Interactions in Human Polyomavirus 7‒Associated Pruritic Skin Eruption.
A phase 3 randomized crossover trial of plerixafor versus G-CSF for treatment of WHIM syndrome
Biography
Diana V. Pastrana, Ph.D.
Dr. Pastrana received her B.S. in biochemistry from Hartwick College in Oneonta, N.Y. She earned her Ph.D. from Johns Hopkins University School of Hygiene and Public Health. Her thesis work at the laboratory of Dr. Alan Scott was on parasitic worms that cause elephantiasis. She identified a homologue of a protein (Macrophage Migration Inhibitory Factor), which allows worms to redirect the host immune response to their advantage. She came to the NIH as a postdoctoral fellow at the Laboratory of Cellular Oncology in 1998, under the leadership of Dr. John Schiller where she developed neutralization tests for papillomaviruses. She became a Staff Scientist in the Laboratory of Molecular Biology in Dr. David FitzGerald's laboratory where she studied a bacterial toxin that can be harnessed to kill certain types of leukemia cells. She returned to the LCO to work with Dr. Christopher Buck, where she works on virus discovery, polyomavirus basic biology/immunology, and vaccine development.
Research
Dr. Pastrana began her research in Dr. Buck’s lab studying Merkel cell polyomavirus (MCPyV), which had recently been shown to cause a rare form of skin cancer. She developed tests to study antibody responses against the virus, enabling serological studies showing that MCPyV infection is very common. The work also produced a number of useful monoclonal antibodies (mAbs) that have been widely shared with other labs and clinical investigators.
In a separate project, Dr. Pastrana discovered that a different polyomavirus species, BKPyV, encompasses five distinct neutralization serotypes. Most people acquire this virus in childhood without any noticeable symptoms. It was believed that after this initial infection, most people developed a lifelong antibody response capable of neutralizing all known BKPyV genotypes. However, Dr. Pastrana’s research showed that some BKPyV genotypes are highly resistant to antibody responses elicited by other BKPyV genotypes. The effect is reminiscent of the now-familiar situation with SARS-CoV-2, where the Omicron genotype is resistant to antibodies elicited by the Delta genotype. Consistent with this analogy, Dr. Pastrana’s discoveries have important implications for polyomavirus-induced disease processes and for BKPyV vaccine development. Her inventions in this area were patented and the intellectual property has been licensed to the biopharmaceutical company Biological E Limited (Hyderabad, India) for commercial development.
Dr. Pastrana has also spearheaded projects aimed at understanding antibody responses against JC polyomavirus (JCPyV), which causes a devastating brain disease in immunosuppressed individuals. Her work revealed a form of neutralizing antibody “blind spots” against disease-associated JCPyV variants.
Dr. Pastrana has also optimized methodologies that facilitated viral discovery, contributing significantly to the expansion of the number of members in the human and animal polyomavirus and papillomavirus families.
Recently, Dr. Pastrana’s interests have shifted to the basic biology of human polyomavirus 7 (HPyV7), a virus she helped discover in 2010. This virus has been associated with acquisition of an unusual form of pruritic (itchy) rash in immunocompromised individuals. Dr. Pastrana has begun to study possible mechanisms that contribute to this pathology and is working toward the development of vaccines and neutralizing mAbs that might be used for treating the disease.