Dr. Silver is a native of Washington, D.C. where received his doctoral degree from the George Washington University School of Medicine. He completed internship and residency training in Internal Medicine at the Columbia Presbyterian Medical Center in New York City and fellowship training in Pulmonary and Critical Care Medicine at the Johns Hopkins University in Baltimore, MD. Dr. Silver came to Cleveland in 1993 specifically to join the large group of tuberculosis (TB) researchers at CWRU and has been a member of the faculty of the Division of Pulmonary, Critical Care, and Sleep Medicine since 1995.
The Silver lab has focused on studying immune responses in the human lung, with particular interest in protective immunity against TB). The primary goal of this work has been to better understand local immune responses to respiratory infection with the TB bacillus, Mycobacterium tuberculosis (MTB). These studies are important for understanding the limitations of the current TB vaccine, the Bacillus of Calmette and Guerin (BCG), which is given to newborns in most of the world as an intradermal (ID) injection. ID BCG is effective at preventing disseminated TB in young children, but has limited and inconsistent efficacy in preventing pulmonary TB.
We utilized bronchoscopy procedures, including the novel procedure of bronchoscopic challenge with the TB skin-test material purified protein derivative (PPD), in studies focused on individuals with latent tuberculosis infection (LTBI), LTBI represents a state in which respiratory MTB infection is been followed by the development of MTB-specific immunity without evidence of active TB disease. This work showed that PPD challenge induced recruitment of additional immune cells into the airways of LTBI participants, but not those of MTB-naïve individuals. Further studies showed that LTBI individuals displayed marked enrichment for MTB-responsive cells within the baseline lung as compared to peripheral blood and demonstrated the role of specific lymphocyte homing molecules in promoting this localization. Collaborative studies with Dr. Daniel Hoft of Saint Louis University proved a long-held hypothesis that recipients of standard ID BCG vaccination did not optimally localize MTB-responsive immune responses into the airways even though strong systemic immunity was observed in these individuals. This finding may explain the limited efficacy of BCG in protecting against pulmonary TB and supports the relevance of studies of LTBI individuals as models of optimized pulmonary immune that would be desirable following more effective approaches to TB vaccination.
Dr. Silver’s research has been sponsored by the Francis Family Foundation, the American Lung Association and American Thoracic Society, the National Heart Lung and Blood Institute of the NIH, and the U.S. Department of Veterans’ Affairs Office of Research and Development. His findings have been published in the official journals of the American Association of Immunologists, the American Society for Microbiology, the Infectious Diseases Society of America, and the American Thoracic Society, as well as by Nature Portfolio.