The focus of Dr. Williams’ research is the basic and clinical investigation of respiratory viruses. Respiratory infections are the leading cause of death in children less than five years old worldwide. Moreover, respiratory infections are a major cause of disease and death in immunocompromised patients such as transplant recipients. The lab’s major area of research is the cell entry, immunity, and pathogenesis of human metapneumovirus (HMPV). HMPV is a recently discovered paramyxovirus that is a leading cause of acute lower respiratory tract illness in infants and children worldwide. HMPV causes severe and fatal disease in high-risk individuals, including premature infants, transplant recipients, older adults, and persons with chronic cardiopulmonary disease. We have a comprehensive program of HMPV research including basic and translational components. We published molecular epidemiology studies establishing the importance of HMPV, in the process isolating dozens of field strains collected over twenty years. We use mouse models to study in vivo pathogenesis and immunity to HMPV. We identified RGD-binding integrins as receptors for HMPV and use a variety of experimental approaches to determine mechanisms of attachment, fusion, and entry.
We have discovered that HMPV and other acute respiratory viral infections cause impairment of lung CD8+ T cells via PD-1 signaling, a pathway previously associated with chronic infections and cancer. Our lab has generated candidate vaccines and monoclonal antibodies against HMPV and identified mechanisms by which HMPV subverts the host innate immune response. We also conduct collaborative studies of the epidemiology of HMPV and other respiratory viruses with investigators at US and international sites.
We have active HMPV research projects in several areas:
- Host and viral determinants of human metapneumovirus immunity and pathogenesis
- Mechanisms by which HMPV and other respiratory viruses lead to impaired pulmonary CD8+ T cells
- Candidate vaccines and therapeutic monoclonal antibodies against HMPV
- Enhanced active surveillance of pediatric infectious diseases and vaccines
- HMPV inhibition of type I interferon responses
The overarching theme of our research on HMPV is to elucidate mechanisms of viral pathogenesis, understand the contribution of host immune responses to pathogenesis, and guide the development of interventions against this important human pathogen.
- John V. Williams, M.D. - Principal Investigator, Chief, Pediatric Infectious Diseases
- Monika Johnson - Lab Manager
- Amy Kinzler - Research Technician
- Kristina Lamens - Graduate Student
- Sara Mascaro – Research Technician
- Margot Miranda-Katz – Research Technician
- Yu Zhang, Ph.D. - Postdoctoral Fellow
Opportunities in the Williams Lab
We are always willing to consider applications from enthusiastic students or postdocs looking to work with us. For more information, please email JVW@chp.edu.