J. Williams Research Group

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 5 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 20 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.