Assistant Professor, Center for Microbial Pathogenesis, Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine
Scholar, Richard King Mellon Institute for Pediatric Research, UPMC Children’s Hospital of Pittsburgh
Education
Graduate School:
2009 PhD, Harvard University, Cambridge, Mass.
Post-Graduate School:
2013 Research Fellow, Vanderbilt University Medical School, Nashville, Tenn.
Biography Summary
Dr. Silva earned an undergraduate degree with a double major in Molecular Biology and Microbiology at Oklahoma State University. She received her Ph.D. in Virology at Harvard University studying viral replication proteins of herpesviruses. Trained as a virologist, Dr. Silva has been studying chikungunya virus for over ten years and leads a research program on the biology of chikungunya virus. Dr. Silva’s research interests are focused on virus-host interactions that dictate chikungunya virus entry, replication within cells, tropism, and pathogenesis. Dr. Silva also serves as the BSL3 Facility Manager for the A-BSL3 Facility at Rangos Research Center.
Research Interests
Chikungunya virus is an emerging, mosquito-borne alphavirus that causes an acute febrile illness called chikungunya fever characterized by a maculopapular rash and incapacitating arthralgia. Acute disease can evolve into chronic arthritis in a substantial subset of patients, with symptoms persisting for months to years. Over the past fifteen years, the geographic range of the virus has expanded drastically, spreading to regions historically free of the virus, including islands in the Indian and Pacific Oceans and numerous countries in the Caribbean and South and Central America. Currently, there are no licensed vaccines or therapeutics to prevent or treat infections caused by chikungunya virus. Addressing knowledge gaps in virus-host interactions and the factors that govern tissue tropism, dissemination, and pathogenesis is critical for development of treatments for this important human pathogen.
The research in my lab centers on virus-host interactions required for chikungunya virus to initiate and complete its replication cycle within cells and establish infection within a host. Using a multidisciplinary approach, we are investigating mechanisms of CHIKV cell entry, replication, and pathogenesis, with the goal of better understanding the viral and host factors that dictate CHIKV virulence, which will inform strategies for the development of antiviral therapeutics and vaccines. Research projects in the lab include:
- Cell entry of CHIKV: Engagement of the host cell surface by a virus is the initial step in viral infection and a critical determinant of viral tropism. Like other alphaviruses, CHIKV binds and infects many cell types, suggesting that CHIKV utilizes a highly conserved, ubiquitous receptor found in mosquitoes and mammals or that multiple receptors are utilized. To understand the host range, tissue tropism, and virulence of this virus, it is critical to elucidate molecular mechanisms of CHIKV attachment and cell entry. We have identified cell-surface glycosaminoglycans (GAGs) as important attachment factors for CHIKV infection. We are now conducting experiments to further define virus-GAG interactions by identifying specific GAG to which CHIKV binds with high affinity and viral determinants required for GAG-binding. Future studies will investigate how virus-glycan interactions influence viral replication, tropism, and pathogenesis.
- Host proteins that mediate viral replication: Viruses are obligate, intracellular parasites and thus require host proteins to facilitate many functions essential for progeny virus production, including entry, formation of viral replication compartments, and virus egress. Understanding the comprehensive repertoire of the host proteome that mediates viral replication is crucial to identify possible therapeutic targets. We have identified several host proteins that promote viral replication and ongoing work in the lab will define the precise steps in viral replication at which the host cell genes function and characterize the biochemical activities that promote infection. This work will illuminate new targets for CHIKV therapeutics.
- Viral tropism, dissemination, and viral pathogenesis: Within the infected mammalian host, CHIKV replicates within numerous tissues and elicits a pathogenic immune response. However, the discrete cell types infected within various tissues and the viral and host determinants that dictate dissemination are not fully understood. Combining traditional virology with next-generation sequencing technologies, we are investigating different mechanisms of infection and dissemination within the host using different models of disease to define factors that influence CHIKV virulence.
View Dr. Silva's full list of publications from PubMed.
