2008 Distinguished Research Career Award
Susan R. Ross, Ph.D., Professor of Microbiology, Associate Dean for Biomedical Graduate Education, and Director of Biomedical Graduate Studies, University of Pennsylvania School of Medicine, Philadelphia, PA
Dr. Susan R. Ross has elucidated several mechanisms that determine susceptibility to retrovirus infection and virus-induced mammary tumors. She answered the question of how retroviruses infect their initial targets in vivo and established that dendritic cells play a crucial role in virus infection. Her discoveries that dendritic cells are the initial targets of MMTV infection and that MMTV activates dendritic and B cells via toll-like receptor 4, a component of the innate immune system, are paradigms that guide studies of human retrovirus infections.
Her studies documented for the first-time a crucial role of intrinsic cellular immunity in viral pathogenesis. In a study published in Nature, Dr. Ross determined that APOBEC3 provides protection to mice against MMTV infection and represent the first demonstration of its protective function against retroviral infection in vivo. She has identified another genetic locus that affects virus spread in lymphocytes by study of dominant susceptibility to MMTV infection in backcrossed strains of mice. Her results obtained from combined functional/genetic approaches are greatly increasing our understanding of the mechanisms that viruses use to infect their hosts and how genetic resistance may occur.
Dr. Ross has evaluated the prevalence of serologic reactivity against MMTVs in women with breast cancer. She mapped the segments of the mouse receptor important for virus infection and confirmed that human TfR1 does not function as an MMTV entry receptor. Dr. Ross determined that the MMTV envelope protein influences breast cancer induction by the activity of immuno-tyrosine based activation motif (ITAM). MMTV that harbors mutation of the ITAM motif are attenuated in mammary tumorigenesis, independently of reduction in infectivity in vivo. By mimicking ITAMs (which are commonly found in receptors expressed in hematopoietic cells and are negatively regulated by cell-type specific modulators) the oncogenic virus envelope protein drives the MMTV transformation process by uncontrolled signaling in epithelial cells. Because ITAMs are found both in viral and cellular proteins, inappropriate expression of such signaling molecules represents a novel mechanism of transformation. These studies guide development of new treatment paradigms for breast and other cancers, especially those associated with viruses that encode proteins to activate ITAM-mediated signaling.
Dr. Ross received the engraved crystal award sculpture and presented the keynote seminar: "Co-evolution of a Virus and its Host: the Mouse as a Model for Understanding Virus-host Interactions." Dr. Ross presented a chalk-talk seminar at the weekly scientific meeting of the Center for Retrovirus Research: "The role of innate immunity in mouse mammary tumor virus infection." The seminars were presented in April 2008 at the College of Veterinary Medicine on the campus of The Ohio State University.
Support for the annual program was jointly provided by the Center for Retrovirus Research, Department of Veterinary Biosciences, Department of Molecular Virology, Immunology and Medical Genetics, and the Comprehensive Cancer Center Viral Oncology Program.
Dr. Susan Ross (right) receives Career Award crystal from Retrovirus Center Director, Dr. Patrick Green
Dr. Susan R. Ross with Dr. Patrick Green