John V. Williams, M.D.
Campus: 4401 Penn Ave
Office: Rangos 9122
Lab: Rangos 9th floor
Pittsburgh, PA 15224
- MD, Medical College of Virginia/Virginia Commonwealth University, 1994
- Residency, Children’s Hospital of Pittsburgh 1997
- Fellowship, Vanderbilt University Medical Center 2000
- Professor, Department of Pediatrics
- Division Chief, Pediatric Infectious Diseases
Respiratory infections are the leading cause of death in children worldwide, and a leading cause of disease in children and adults in developed nations. The focus of my research is the basic and clinical investigation of respiratory viruses. Our major area of investigation is the cell entry, immunity, and pathogenesis of human metapneumovirus (HMPV). HMPV, a paramyxovirus discovered in 2001, is a leading cause of acute lower respiratory illness in infants, children, the elderly, and persons with underlying medical conditions. There are no licensed antivirals or vaccines for HMPV and little is known about protective immunity and viral pathogenesis.. We seek to understand the immunobiology of this important human pathogen, to elucidate mechanisms of lung CD8+ T cell impairment, and to facilitate the development of preventive and therapeutic strategies.
We also conduct collaborative research with clinical investigators at Vanderbilt and international sites. We have participated in studies of respiratory virus epidemiology in North America, South America, the Middle East, and Africa. Our group has published studies on coronaviruses, influenza virus, HMPV, parainfluenza viruses, respiratory syncytial virus, and rhinoviruses in diverse populations. We have several ongoing collaborations with clinical researchers in respiratory virus epidemiology.
Specific HMPV research projects include:
- Mechanisms by which HMPV and other respiratory viruses lead to impaired pulmonary CD8+ T cells
- Candidate vaccines and therapeutic monoclonal antibodies against HMPV
- High-throughput screening for small molecule inhibitors of HMPV
- HMPV inhibition of type I interferon responses
- Integrin-mediated entry of HMPV
- Human T cell responses to HMPV
Cox RG, Mainou B, Johnson M, Hastings AK, Schuster JE, Dermody TS, Williams JV. Human Metapneumovirus is Capable of Entering Cells by Fusion with Endosomal Membranes. (2015) PLOS Pathog. in press.
Erickson JJ, Lu P, Wen SC, Hastings AK, Gilchuk P, Joyce J, Shyr Y, Williams JV. (2015) Acute viral respiratory infection rapidly induces a CD8+ T cell exhaustion-like phenotype. J Immunol. In press. | View Abstract
Wen SC, Schuster JE, Gilchuk P, Boyd KL, Joyce J, Williams JV. (2015) Lung CD8+ T cell impairment occurs during human metapneumovirus infection despite virus-like particle (VLP) induction of functional CD8+ T cells. J Virol. 89:8713-26. | View Abstract
Schuster JE, Cox RG, Hastings AK, Boyd KL, Wadia J, Chen Z, Burton DR, Williamson RA, Williams JV. (2015) A broadly neutralizing human monoclonal antibody exhibits in vivo efficacy against both human metapneumovirus and respiratory syncytial virus. J Infect Dis. 211: 216-225. | View Abstract
Hastings AK, Erickson JJ, Schuster JE, Boyd KL, Tollefson SJ, Johnson M, Gilchuk P, Joyce S, Williams JV. (2015) Role of type I interferon signaling in human metapneumovirus pathogenesis and control of viral replication. J Virol. 89: 4405-4420. | View Abstract
Cox RG, Erickson JJ, Hastings AK, Becker JC, Craven RE, Tollefson SJ, Boyd KL, Williams JV. Human Metapneumovirus Virus-like Particles Induce Protective B and T cell Responses in a Mouse Model. (2014) J Virol. 88(11):6368-79. View Abstract
Erickson JJ, Rogers MC, Hastings AK, Tollefson SJ, Williams JV. (2014) PD-1 Impairs Secondary Effector Lung CD8+ T Cells during Respiratory Virus Reinfection. J Immunol 193(10):5108-17. | View Abstract
Wen SC, Tollefson SJ, Johnson M, Gilchuk P, Boyd KL, Shepherd B, Joyce S, Williams JV. (2014) Acute Clearance of Human Metapneumovirus Occurs Independently of Natural Killer Cells. J Virol. 88(18):10963-9. | View Abstract
Edwards KM, Zhu Y, Griffin MR, Weinberg GA, Hall CB, Szilagyi PG, Staat MA, Iwane M, Prill MM, Williams JV. The burden of human metapneumovirus infection in young children. N Engl J Med. 368:633-43. | View Abstract
Erickson JJ, Gilchuk P, Hastings AK, Tollefson, SJ, Johnson M, Downing MB, Boyd KL, Johnson JE, Kim AS, Joyce S, Williams JV. (2012) Viral acute lower respiratory infections impair CD8+ T cells through PD-1. J Clin Invest. 122: 2967-2982. | View Abstract
Cox RG, Livesay SB, Johnson M, Ohi MD, Williams JV. (2012) The human metapneumovirus fusion protein mediates entry via an interaction with RGD-binding integrins. J Virol. 86: 12148-12160. | View Abstract
Cseke G, Maginnis MS, Cox RG, Tollefson SJ, Podsiad AB, Wright DW, Dermody TS, Williams JV. (2009) Integrin alphavbeta1 promotes infection by human metapneumovirus. Proc Natl Acad Sci USA. 106: 1566-1571. | View Abstract
Note: trainee authors underlined